Co-reporter:Di Wu, Yonghui Zheng, Xiuli Hu, Zhimin Fan, Xiabin Jing
Materials Science and Engineering: C 2015 Volume 53() pp:68-75
Publication Date(Web):1 August 2015
DOI:10.1016/j.msec.2015.04.012
•Folic acid-bearing polymer–PTX micelles showed higher inhibition rates of tumor growth.•The percentage of cell apoptosis of M(FA/PTX) was highest among drug groups.•Bcl-2 expression was down-regulated in the drug group.•Bax expression was up-regulated in the drug group.•In M(FA/PTX) group, the survival time was prolonged.BackgroundPaclitaxel (PTX) is a first line chemotherapy drug for breast cancer. There have been few studies reported concerning the therapeutic efficacy of paclitaxel-conjugated polymeric micelles in breast cancer in vivo.MethodsTwo kinds of PTX conjugate micelles, one of which (M(PTX)) contained 25 wt.% of PTX and the other (M(FA/PTX)) contained 22.5 wt.% of PTX and 1.4 wt.% of folate (FA), were prepared for cell apoptosis and anti-tumor activity evaluation on EMT-6 mice breast cancer models in comparison with 0.9 wt.% saline (control) and equivalent PTX. Cell apoptosis was analyzed by flow cytometry. Breast tumors were examined histologically with H&E staining and immunohistochemically by examining Bax and Bcl-2 expression. The survival status of tumor-bearing mice with different treatments was also examined.ResultsOn day 5 of the drug administration, the average tumor masses were 0.49, 0.33, 0.22, and 0.18 g for the control, PTX, M(PTX) and M(FA/PTX) groups, respectively. The inhibition rates of tumor growth calculated for the three drug groups were 32.6%, 51.6% and 62.3%, respectively. The percentage of cell apoptosis based on flow cytometry was 1.0%, 36.6%, 55.9% and 66.1%, respectively, which showed statistically significant differences (p < 0.05) between three drug groups and the control group. Bcl-2 expression of PTX and M(FA/PTX) groups was lower than control group (p < 0.05). Bax expression of drug groups was higher than control group (p < 0.05). At an equivalent paclitaxel dose of 26.7 mg/kg, the average survival time was 33 days, 31 days, 34 days and 42 days, respectively (p < 0.05).ConclusionThe M(FA/PTX) have better anti-tumor activity and are promising in treatment of human breast cancers.
Co-reporter:Jun Yue, Shi Liu, Zhigang Xie, Ying Xing and Xiabin Jing
Journal of Materials Chemistry A 2013 vol. 1(Issue 34) pp:4273-4280
Publication Date(Web):25 Jun 2013
DOI:10.1039/C3TB20296H
The fate of polymeric micelles (PMs) is mainly determined by their physicochemical properties, such as particle size, shape, and surface potential. Of these factors, the size effect of PMs plays a fundamental role. In this study, four different sizes of PMs with fluorescence-labeling were prepared to study the size-dependent biodistribution profiles as well as the anti-tumor efficacy in H22-subcutaneous hepatoma-bearing mice. Both ex vivo tumor imaging and in vivo real-time near-infrared (NIR) dye-tracking experiments indicated that sub-100 nm PMs have a higher extent of accumulation in tumor sites than >100 nm PMs. For normal tissues, smaller PMs (35 nm) tend to accumulate in the kidney and larger PMs (145 nm) tend to be captured by the spleen and lung, while middle-sized PMs (75 and 115 nm) tend to accumulate in the liver. Finally, doxorubicin (Dox) was used as the model drug to study the size-dependent anti-tumor efficacy of Dox-loaded micelles with H22-bearing mice and the results indicated that the smallest micellar drugs exhibited the best tumor-growth inhibition effect.
Co-reporter:Haiqin Song, Haihua Xiao, Yu Zhang, Haidong Cai, Rui Wang, Yonghui Zheng, Yubin Huang, Yuxin Li, Zhigang Xie, Tongjun Liu and Xiabin Jing
Journal of Materials Chemistry A 2013 vol. 1(Issue 6) pp:762-772
Publication Date(Web):27 Nov 2012
DOI:10.1039/C2TB00206J
A multifunctional hybrid platinum(IV) drug which has both DCA and Pt in one molecule was synthesized and tethered to polymers to further self-assemble into micelles. This micelle-mediated delivery of platinum(IV) prodrug aims to target both nuclear DNA and mitochondria.
Co-reporter:Xiuli Hu;Lesan Yan;Haihua Xiao;Xiaoyuan Li
Journal of Applied Polymer Science 2013 Volume 127( Issue 5) pp:3365-3373
Publication Date(Web):
DOI:10.1002/app.37662
Abstract
The aim of this study is to develop azido-carrying biodegradable polymers and their postfunctionalization with alkynyl compounds via click chemistry and to investigate their potential use in drug delivery. Azido polymers were prepared by ring-opening polymerization of cyclic carbonate monomer, 2,2-bis(azidomethyl)trimethylene carbonate (ATC) with lactide using stannous octoate as catalyst. Several alkynyl compounds were selected to investigate the feasibility and reaction condition of click chemistry. With microwave-assisting, the reaction time of click chemistry was shortened to 5 min. By using poly(ethylene glycol) (PEG) as macroinitiator, amphiphilic block copolymer mPEG-b-P(LA-co-ATC) was obtained and it could self-assemble into micelles by solvent replacement method. The pendant groups were used for conjugating anticancer drugs gemcitabine and paclitaxel and fluorescent dye Rhodamine B. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to assay the cytotoxicity of the conjugate micelles against SKOV-3 and HeLa cell lines. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Co-reporter:Ruo-gu Qi;Su-hong Wu;Yu Wang;Jie Chen
Chinese Journal of Polymer Science 2013 Volume 31( Issue 6) pp:912-923
Publication Date(Web):2013 June
DOI:10.1007/s10118-013-1288-6
To further enhance the transfection efficiency of a micelleplex system based on monomethoxy poly(ethylene glycol)-block-poly(ɛ-caprolactone)-block-poly(L-lysine) (MPEG-b-PCL-b-PLL), cholesterol (Chol) moieties are attached to the ɛ-termini of PLL segments to obtain MPEG-b-PCL-b-PLL/Chol. The structure and morphology of the copolymer are studied by 1H-NMR, TEM and DLS (dynamic light scattering). The cytotoxicity, cell uptake, endosomal release and mRNA knockdown are studied by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, flow cytometry, CLSM (confocal laser scanning microscopy) and RT-PCR (real-time polymerase chain reaction). The results show that compared to their precursor MPEG-b-PCL-b-PLL, the cholesterol-grafted copolymer shows significantly lower toxicity, more rapid cellular endocytosis and endosome escape, and consequently displays enhanced siRNA transfection efficiency even at a lower N/P ratio. These improvements are ascribed to enhanced interaction of the cholesterol moieties with both cellular membrane and endosomal membrane. Moreover, effect of the PLL block length is examined. The final conclusion is that long enough PLL segments and incorporation of proper fraction of cholesterol onto the PLL segments benefit the enhancement of siRNA transfection efficiency.
Co-reporter:Xiuli Hu, Rui Wang, Jun Yue, Shi Liu, Zhigang Xie and Xiabin Jing
Journal of Materials Chemistry A 2012 vol. 22(Issue 26) pp:13303-13310
Publication Date(Web):01 May 2012
DOI:10.1039/C2JM31130E
Multifunctional micelles were successfully prepared by co-assembling a Doxorubicin-conjugated copolymer (mPEG-b-P(LA-co-ME/Dox), for antitumor properties) and a Rhodamine B-conjugated copolymer (mPEG-b-P(LA-co-ME/RhB), for imaging) with a folic acid (FA)-conjugated copolymer (FA-PEG-b-PLA, for targeting), respectively. DLS showed that the sizes of these micelles were in the range of 150–300 nm. Fluorescent imaging analysis based on the RhB signals of the isolated visceral organs showed that the micelles with or without FA moieties were mainly accumulated in the liver and in the tumor from 2 h post drug administration, maximized at ca. 6 h, and decayed afterwards. More FA-carrying micelles were accumulated in the tumor for a longer time compared to the micelles without FA moieties. Dox-containing micelles were used for tumor inhibition experiments in vivo and the results showed that the micelles with FA moieties exhibited better antitumor efficacy than those without FA and free Dox.
Co-reporter:Wenliang Li, Wenjing Zhang, Xiaoqing Dong, Lesan Yan, Ruogu Qi, Weicai Wang, Zhigang Xie and Xiabin Jing
Journal of Materials Chemistry A 2012 vol. 22(Issue 34) pp:17445-17448
Publication Date(Web):16 Jul 2012
DOI:10.1039/C2JM32778C
A porous heterogeneous photocatalyst was prepared by high internal phase emulsion (HIPE) polymerization. Such porous materials have interconnected pores and enough active moieties for photocatalysis. The material demonstrated a very high catalytic efficiency and can be reused for photocatalyzed oxidation of thioanisole under visible light.
Co-reporter:Ruogu Qi, Suhong Wu, Haihua Xiao, Lesan Yan, Wenliang Li, Xiuli Hu, Yubin Huang and Xiabin Jing
Journal of Materials Chemistry A 2012 vol. 22(Issue 36) pp:18915-18922
Publication Date(Web):31 Jul 2012
DOI:10.1039/C2JM33141A
The lack of safe and effective carriers for RNA interference therapeutics remains a barrier for its wide clinical application. In this study, guanidino groups were incorporated into poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(L-lysine) (mPEG-b-PCL-b-PLL, AG0) by simple replacement of the amino groups on PLL segments by the guanidino groups to enhance the transfection performance by mimicking the transmembrane function of cell penetrating peptides, such as TAT or other arginine-rich peptides. The guanidinated copolymers (AG1–AG3) displayed similar siRNA-binding capacity to AG0, but less cytotoxicity and higher silencing efficiency than AG0. Typically, AG3 with full replacement of the amino groups by guanidino groups exhibited higher silencing efficiency than PEI-25k and Lipofectamine 2000. Cell uptake and cell imaging experiments showed that the enhanced silencing efficiency of AG3–siRNA complex was due to the enhanced endocytosis cross the cell-membrane and the enhanced escape from the endosomes/lyosomes. The guanidino groups on the polylysine units were responsible for these enhancements although they are attached to the polymer backbone with a spacer of (CH2)4, in comparison with (CH2)3 in polyarginine. In conclusion, guanidination of mPEG-b-PCL-b-PLL resulted in a less toxic and more efficient siRNA vector and contribution of the guanidine groups to cell-membrane penetration and endosome/lyosome-membrane penetration was demonstrated. Therefore, replacement of the amino groups in conventional gene delivery vectors with guanidine groups might be a useful strategy of developing novel gene or drug delivery vectors.
Co-reporter:Haihua Xiao, Lesan Yan, Yu Zhang, Ruogu Qi, Wenliang Li, Rui Wang, Shi Liu, Yubin Huang, Yuxin Li and Xiabin Jing
Chemical Communications 2012 vol. 48(Issue 87) pp:10730-10732
Publication Date(Web):26 Sep 2012
DOI:10.1039/C2CC34297A
A multifunctional hybrid platinum(IV) prodrug, which consists of both the mitochondria-targeting drug DCA and the DNA-crosslinking drug cisplatin, was synthesized and tethered to a carrier polymer to further self-assemble into micelles for intracellular delivery.
Co-reporter:Haihua Xiao, Wenliang Li, Ruogu Qi, Lesan Yan, Rui Wang, Shi Liu, Yonghui Zheng, Zhigang Xie, Yubin Huang, Xiabin Jing
Journal of Controlled Release 2012 Volume 163(Issue 3) pp:304-314
Publication Date(Web):10 November 2012
DOI:10.1016/j.jconrel.2012.06.004
An oxaliplatin pro-drug (Oxa(IV)–COOH) with an axial carboxyl group was synthesized and conjugated to biodegradable polymers with pendant hydroxyl groups to prepare polymer–Oxa(IV) conjugates. A hydrophobic anthracycline-based drug, daunorubicin (DRB) was conjugated to similar biodegradable polymers with carboxyl groups to synthesize polymer–DRB conjugates. The two drug conjugates have the similar polymer backbone and are amphiphilic; thus, they can co-assemble into composite micelles. In the composite micelles, the polymer–Oxa(IV) conjugates can release clinically widely used water soluble anticancer drug oxaliplatin (Oxa(II)) upon reduction, while polymer–DRB conjugate is thought to release DRB via acid hydrolysis in the cancer cells. In this way, combination of the hydrophilic platinum drug Oxa(II) and hydrophobic drug DRB can be realized by delivering them in one platform. Moreover, the composite micelles showed reduced systematic toxicity and greater synergistic effect than combination of small molecules of the two anticancer drugs both in vitro and in vivo; thus, this polymer based combination therapy can be useful in future clinic application.A new hydrophilic pro-drug, Oxa(IV)–COOH, was prepared and attached to a biodegradable amphiphilic polymer to form polymer–Oxa(IV) conjugate. Then it was co-assembled with polymer–danuorubicin (polymer–DRB) conjugates to mixed micelles(M(DRB/Oxa(IV)). In this way, both DRB and Oxa(IV) complex will be located in the core part of the micelles and get effectively protected. Once they enter the cancerous cells, due to the drastic drop in pH and increase in the concentration of reducing agent such as GSH and ascorbic acid, both DRB and active platinum(II) species will be released from the micelles by hydrolysis and reduction respectively. Then, the released DRB undergo further insertion into the DNA strand and Pt drugs go to cross‐link with DNA respectively. In this way, they were combined to promote cell to death more effectively. Because DRB and Oxa(IV) complex are attached to different polymer chains, their relative doses can be adjusted easily. Furthermore, synergetic effect of the composite micelles proved to be realized in vitro and in vivo. Safer and more efficacious combination therapy can be realized with this strategy.
Co-reporter:Lesan Yan, Wenbin Wu, Wei Zhao, Ruogu Qi, Dongmei Cui, Zhigang Xie, Yubin Huang, Ti Tong and Xiabin Jing
Polymer Chemistry 2012 vol. 3(Issue 9) pp:2403-2412
Publication Date(Web):13 Jun 2012
DOI:10.1039/C2PY20240A
A functionalized six-membered cyclic carbonate monomer containing a protected thiol group, 2-(2,4-dinitrophenylthio)ethyl-5-methyl-2-oxo-1,3-dioxane-5-carboxylate (MTC), was prepared. Ring-opening polymerization (ROP) of MTC and L-lactide (LA) initiated by monohydroxyl poly(ethylene glycol) (mPEG) was successfully performed with controlled polymer molecular weight and molecular weight distribution. The structures of the obtained monomer and copolymers were confirmed by NMR and FTIR. After deprotection under mild conditions, the amphiphilic block copolymer was self-assembled into micelles in aqueous solution. By oxidation of the free thiol groups in the PMTC segments, the micelles with the cross-linked core were formed, and the enhanced stability against disruptive conditions was demonstrated by dynamic light scattering (DLS) measurement in the presence of DMF. Doxorubicin (DOX) was loaded into the micelles as a model drug. The in vitro DOX release behaviors indicated that cross-linking of the micelle cores resulted in a slow drug release and this process was greatly accelerated by adding glutathione (GSH) solution with comparable concentrations to intracellular levels in tumor cells. The cross-linked micelles were demonstrated to be efficiently internalized into the cells. Faster intracellular DOX release was observed by confocal laser scanning microscopy (CLSM) in the GSH pretreated MCF-7 cells than in the unpretreated MCF-7 cells. In vitro MTT assay revealed that the cross-linked micelles were biocompatible with L929 cells and MCF-7 cells. As expected, DOX-loaded cross-linked micelles showed higher cellular proliferation inhibition towards glutathione pretreated MCF-7 cells than that towards the unpretreated ones at various GSH concentrations. These results indicated that the bioreducible core-cross-linked micelles can be used as drug carriers for intelligent drug delivery.
Co-reporter:Haihua Xiao, Dongfang Zhou, Shi Liu, Yonghui Zheng, Yubin Huang, Xiabin Jing
Acta Biomaterialia 2012 Volume 8(Issue 5) pp:1859-1868
Publication Date(Web):May 2012
DOI:10.1016/j.actbio.2012.01.007
Abstract
A biodegradable and amphiphilic copolymer, MPEG-b-P(LA-co-MCC), which contains pendant carboxyl groups, was chosen as a drug carrier for the active anticancer part (DACH-Pt) of oxaliplatin to form an MPEG-b-P(LA-co-MCC/Pt) complex. It was able to self-assemble into micelles with a mean diameter of 30–40 nm, and a surface potential near -10 mV. The typical platinum content was 10 wt.%. The micelles showed acid-responsive drug release kinetics, which is beneficial for drug release in the intracellular environment. The Pt(II) species were released mainly in the form of DACH-Pt-Cl2 in 150 mM NaCl solution and DACH-Pt2+-(H2O)2 in pure water according to the results obtained by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy. In vitro evaluation showed that the micelles displayed the same or higher cytotoxicities against SKOV-3, HeLa, and EC-109 cancer cells compared with oxaliplatin. The enhanced cytotoxicity against SKOV-3 cells is attributed to effective internalization of the micelles by the cells via endocytosis and the sensitivity of SKOV-3 cells to platinum drugs. This novel biodegradable and amphiphilic copolymer-based platinum drug will have great potential application in clinical use.
Co-reporter:Lesan Yan, Lixin Yang, Hongyan He, Xiuli Hu, Zhigang Xie, Yubin Huang and Xiabin Jing
Polymer Chemistry 2012 vol. 3(Issue 5) pp:1300-1307
Publication Date(Web):23 Mar 2012
DOI:10.1039/C2PY20049J
A functionalized L-glutamate N-carboxyanhydride monomer containing a cinnamyl moiety, γ-cinnamyl-L-glutamate N-carboxyanhydride (CLG-NCA), was prepared. Ring-opening polymerization (ROP) of CLG-NCA initiated by n-hexylamine and amino-terminated poly(ethylene glycol) (mPEG-NH2) was successfully performed with controlled polymer molecular weight and molecular weight distribution. The structures of the obtained monomer and polymers were confirmed by 1H NMR, 13C NMR and FTIR. The block copolymer mPEG-b-PCLG could self-assemble into micelles in aqueous solution which consist of a hydrophobic PCLG core and a hydrophilic mPEG shell. Under UV-irradiation at 254 nm, the photo-cross-linking process of the cinnamyl-carrying block copolymer micelles was tracked by UV-Vis spectra, 1H NMR, dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro MTT assay demonstrated that the micelles were biocompatible to L929 cells. Paclitaxel was loaded into the micelles as a model drug. The in vitro paclitaxel release behaviors indicated that cross-linking of the micelle cores results in a slow drug release in comparison with the non-cross-linked micelles. These results indicated that the photo cross-linked mPEG-b-PCLG micelles can be used as drug carriers for intelligent drug delivery.
Co-reporter:Jun Yue, Shi Liu, Rui Wang, Xiuli Hu, Zhigang Xie, Yubin Huang, and Xiabin Jing
Molecular Pharmaceutics 2012 Volume 9(Issue 7) pp:1919-1931
Publication Date(Web):May 22, 2012
DOI:10.1021/mp300213g
As the transport protein for iron, transferrin can trigger cellular endocytosis once binding to its receptor (TfR) on the cell membrane. Using this property, we conjugated transferrin onto the surface of biodegradable polymeric micelles constructed from amphiphilic block copolymers. The core of micelle was either labeled with a near-infrared dye (NIR) or conjugated with a chemotherapeutic drug paclitaxel (PTX) to study the biodistribution or antitumor effect in nude mice bearing subcutaneous TfR-overexpressing cancers. DLS and TEM showed that the sizes of Tf-conjugated and Tf-free micelles were in the range of 85–110 nm. Confocal laser scanning microscopy and flow cytometry experiments indicated that the uptake efficiency of the micelles by the TfR-overexpressing cells was enhanced by Tf conjugation. Semiquantitative analysis of the NIR signals collected from the tumor site showed that the maximum accumulation was achieved at 28 h in the M(NIR) group, while at 22 h in Tf–M(NIR) groups; and the area under the intensity curve in the Tf–M(NIR) groups was more than that in M(NIR) group. Finally, the tumor inhibition effects of targeting micelles were studied with the gastric carcinoma model which overexpressed TfR. The analysis of tumor volumes and the observation of H&E-stained tumor sections showed that Tf–M(PTX) had the best antitumor effect compared with the control groups (saline, PTX, and M(PTX)). The results of this study demonstrated the potential application of Tf-conjugated polymeric micelles in the treatment of TfR-overexpressing cancers.Keywords: antitumor effect; micelle; paclitaxel; TfR; transferrin;
Co-reporter:Jun Yue, Rui Wang, Shi Liu, Suhong Wu, Zhigang Xie, Yubin Huang and Xiabin Jing
Soft Matter 2012 vol. 8(Issue 28) pp:7426-7435
Publication Date(Web):15 Jun 2012
DOI:10.1039/C2SM25456E
Biodegradable Y-shaped amphiphilic block copolymer mPEG-b-PLG-b-(PLA)2 was synthesized and characterized by 1H NMR and FTIR. The amphiphilic property of the copolymer with a mPEG-b-PLG segment as the hydrophilic arm and two PLA segments as the hydrophobic arms endows the copolymer with the ability to form core–shell nanoparticles in aqueous solution. Co-assembly of doxorubicin (Dox) and the block copolymer in selective solvent was carried out to prepare Dox-loaded micelles. The inner-shell (PLG) of the micelle was crosslinked through a carbodiimide coupling method with cystamine as the crosslinker. The crosslinked micelles exhibit reduction-responsive release of Dox and the stability in vitro was much better than non-crosslinked micelles. In acidic release condition, the total amount of Dox released could be increased due to the increased solubility of Dox. The blood clearance of Dox in different form of micelles was studied and the results show that Dox loaded in the crosslinked micelles with PEG5K as the outer shell exhibit the longest blood circulation after intravenous injection.
Co-reporter:Jun Yue;Shi Liu;Rui Wang;Xiuli Hu;Zhigang Xie;Yubin Huang
Macromolecular Bioscience 2012 Volume 12( Issue 9) pp:1209-1219
Publication Date(Web):
DOI:10.1002/mabi.201200037
Co-reporter:Haihua Xiao;Dongfang Zhou;Shi Liu;Ruogu Qi;Yonghui Zheng;Yubin Huang
Macromolecular Bioscience 2012 Volume 12( Issue 3) pp:367-373
Publication Date(Web):
DOI:10.1002/mabi.201100320
Co-reporter:Haihua Xiao, Haiqin Song, Qiang Yang, Haidong Cai, Ruogu Qi, Lesan Yan, Shi Liu, Yonghui Zheng, Yubin Huang, Tongjun Liu, Xiabin Jing
Biomaterials 2012 33(27) pp: 6507-6519
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.05.049
Co-reporter:Haihua Xiao, Haiqin Song, Yu Zhang, Ruogu Qi, Rui Wang, Zhigang Xie, Yubin Huang, Yuxin Li, Yin Wu, Xiabin Jing
Biomaterials 2012 33(33) pp: 8657-8669
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.08.015
Co-reporter:Daxing Liu, Shi Liu, Xiabin Jing, Xiaoyuan Li, Wenliang Li, Yubin Huang
Biomaterials 2012 33(17) pp: 4362-4369
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.02.062
Co-reporter:Haijun Yu;Chao Deng;Huayu Tian;Tiancheng Lu;Xuesi Chen
Macromolecular Bioscience 2011 Volume 11( Issue 3) pp:
Publication Date(Web):
DOI:10.1002/mabi.201000283
Co-reporter:Guojun Mo;Jun Yue;Ping'an Ma;Xuesi Chen;Yubin Huang
Polymer International 2011 Volume 60( Issue 8) pp:1269-1276
Publication Date(Web):
DOI:10.1002/pi.3074
Abstract
Amphiphilic amino-bearing biodegradable copolymers, [methoxy-poly(ethylene glycol)]-block-poly[(L-lactide)-co-(serinol carbonate)] (mPEG-block-P(LA-co-CA)), are prepared by synthesizing amino-bearing cyclic carbonate monomer N-benzoxycarbonylserinol carbonate (CAB) starting from serinol, by ring-opening polymerization of L-lactide and CAB using diethylzinc as catalyst and mPEG as macroinitiator, and by subsequent removal of the protective benzyloxycarbonyl groups by HBr treatment. After deprotection, the pendant amino groups on the carbonate units are reacted with N-hydroxylsuccinimide-activated folic acid (FA) to achieve mPEG-block-P(LA-co-CA/FA) conjugate and with fluorescein isothiocyanate (FITC) to achieve mPEG-block-P(LA-co-CA/FITC) conjugate. The structures of mPEG-block-P(LA-co-CAB), mPEG-block-P(LA-co-CA), mPEG-block-P(LA-co-CA/FA) and mPEG-block-P(LA-co-CA/FITC) are confirmed using 1H NMR and Fourier transform infrared spectroscopy. The block copolymers can self-assemble into micelles in aqueous solution. Because of the functionality of FA and FITC, these copolymers can find important applications in drug delivery systems to serve as targeting moieties and fluorescent probes. Copyright © 2011 Society of Chemical Industry
Co-reporter:Jizheng Wei, Lesan Yan, Xiuli Hu, Xuesi Chen, Yubin Huang, Xiabin Jing
Colloids and Surfaces B: Biointerfaces 2011 Volume 83(Issue 2) pp:220-228
Publication Date(Web):1 April 2011
DOI:10.1016/j.colsurfb.2010.11.020
Fourier transform surface plasmon resonance (FT-SPR) was utilized to study specific and non-specific interactions between proteins and a biotinylated polymer film by monitoring adsorptions of streptavidin (SAv) and bovine serum albumin (BSA) on the polymer films. The biotinylated polymer, poly(lactide-co-2,2-dihydroxymethyl-propylene carbonate-graft-biotin) [P(LA-co-DHC/biotin)], was prepared by ring-opening copolymerization of lactide and a OH-bearing cyclic carbonate monomer, followed by biotinylation of the OH groups. The copolymer was coated onto the FT-SPR chip and vacuum-dried, hydrated at 70 °C, and treated with a blocking agent respectively to achieve different surface status. The FT-SPR results showed that the vacuum-dried film had the most BSA adsorption; hydration treatment led to migration of the biotin moieties from inner film to surface and thus resulted in less BSA adsorption; blocking layer on the polymer surface saturated the active sites for physical and chemical adsorptions on the surface and thus weakened the BSA adsorption. Adsorption of SAv displayed similar polymer-surface-status dependence, i.e., more adsorption on vacuum-dried surface, less adsorption on hydrated surface and the least adsorption on blocked surface. Compared with BSA, SAv showed more enhanced adsorptions on P(LA-co-DHC/biotin) surface because of the specific interaction of biotin moieties in the polymer with SAv molecules, especially on the blocked surface. The above semi-quantified results further indicate that the FT-SPR system is suitable for investigating interactions between polymer surface and bio-molecules.Graphical abstractFourier transform surface plasmon resonance (FT-SPR) was utilized to study specific and non-specific interactions between proteins and a biotinylated polymer film by monitoring adsorptions of streptavidin (SAv) and bovine serum albumin (BSA) on the polymer films. It showed that the vacuum-dried film had the strongest BSA adsorption; hydration treatment resulted in less BSA adsorption; and the blocked layer had the weakest adsorption. The SAv binding on the surfaces displayed similar polymer-surface-status dependence, while compared with BSA, SAv showed more enhanced adsorptions on P(LA-co-DHC/biotin) surface because of the specific interaction of biotin moieties in the polymer with SAv molecules, especially on the blocked surface.Research highlights▶ A biotinylated polymer, poly(lactide-co-2,2-dihydroxymethyl-propylene carbonate-graft-biotin) [P(LA-co-DHC/biotin)] was synthesized and served as a model polymer, on which co-existed non-specific protein adsorption and specific interaction. ▶ Three different treatment were used to modify the polymer film to let the films had different properties. ▶ A newly developed technology, Fourier transform surface plasmon resonance (FT-SPR) was utilized to study specific and non-specific interactions between proteins and a biotinylated polymer film by monitoring adsorptions of streptavidin (SAv) and bovine serum albumin (BSA) on the polymer films at the same time. ▶ The hydration treatment led to migration of the biotin moieties from inner film to surface and thus resulted in less BSA adsorption and more SAv binding. ▶ Blocking layer on the polymer surface saturated the active sites for physical and chemical adsorptions on the surface and thus the non-specific adsorption of BSA was the weakest, while the specific binding of SAv on the blocked film was relatively the highest.
Co-reporter:Haihua Xiao, Ruogu Qi, Shi Liu, Xiuli Hu, Taicheng Duan, Yonghui Zheng, Yubin Huang, Xiabin Jing
Biomaterials 2011 32(30) pp: 7732-7739
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.06.072
Co-reporter:Lixin Yang, Jizheng Wei, Lesan Yan, Yubin Huang, and Xiabin Jing
Biomacromolecules 2011 Volume 12(Issue 6) pp:
Publication Date(Web):April 14, 2011
DOI:10.1021/bm2003658
A series of biodegradable polyurethanes containing free side hydroxyl groups (PUOH) were synthesized successfully in two steps: (1) PLA diol as soft segment, hexamethylene diisocyanate (HDI) as hard segment, and benzalpentaerythritol (BPO) as a chain extender were used to synthesize PUs with protected OH groups; (2) CF3COOH was used as a deprotection agent to remove the benzal groups on PU to prepare PUOH. The properties of PU and PUOH were characterized by Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), water contact angle measurement, and gel permeation chromatography (GPC). The benzal groups were removed completely in 15 min without detrimental effect on PU main chains to obtain PUOHs. 4-Azidobenzoic acid was conjugated to PUOH through its esterification with the free OH groups on PUOH. The results of immunofluorescence assay showed that the phenyl azide groups formed were capable of binding mouse IgG under UV (254 nm) irradiation in 3 min; the bound mouse IgG retained its own biological activity and could further bind the FITC-labeled anti(mouse IgG). Therefore, this material has a potential in immunofluorescence assay and related fields.
Co-reporter:Jing Sun;Xuesi Chen;Jizheng Wei;Lesan Yan
Journal of Applied Polymer Science 2010 Volume 118( Issue 3) pp:
Publication Date(Web):
DOI:10.1002/app.32341
Abstract
A novel approach to self-assembled and shell-crosslinked (SCL) micelles from the diblock copolymer poly(L-lactide)-block-poly(L-cysteine) to be used as drug and protein delivery carriers is described. Rifampicin was used as a model drug. The drug-loaded SCL micelles were obtained by self-assembly of the copolymer in the presence of the drug in aqueous media. Their morphology and size were studied with dynamic light scattering and field emission scanning electron microscopy. The rifampicin loading capacity and encapsulation efficiency were studied with ultraviolet–visible spectrophotometry. The drug-release rate in vitro depended on the oxidizing and reducing environment. Moreover, a straightforward approach to the conjugation of the copolymer with bovine serum albumin (BSA) was developed, and a gel electrophoresis test demonstrated that this conjugated BSA could be reversibly released from the copolymer substrate under reducing conditions. In conclusion, this L-cysteine copolymer can be used in drug delivery and in protein fixation and recovery. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Co-reporter:Xiaoqing Dong, Yonghui Zheng, Yubin Huang, Xuesi Chen, Xiabin Jing
Analytical Biochemistry 2010 Volume 405(Issue 2) pp:207-212
Publication Date(Web):15 October 2010
DOI:10.1016/j.ab.2010.06.022
Multifunctional poly(glycidyl methacrylate) (PGMA) microspheres containing magnetic, fluorescent, and cancer cell-specific moieties were prepared in four steps: (i) preparation of parent PGMA microspheres by dispersion polymerization and their reaction with ethylenediamine to obtain amino groups, (ii) precipitation of iron ions (Fe2+ and Fe3+) to form Fe3O4 nanoparticles within the microspheres, (iii) consecutive reactions of folic acid with the amino groups on PGMA, and (iv) incorporation of fluorescein isothiocyanate into the microspheres. The microspheres were superparamagnetic, highly monodispersive, intensively fluorescent, and capable of recognizing and binding cancer cells that overexpress folic acid receptors. It was demonstrated that with these microspheres, HeLa cells could be captured from their suspension and easily moved in the direction of the externally applied magnetic field.
Co-reporter:Ping'an Ma, Shi Liu, Yubin Huang, Xuesi Chen, Liping Zhang, Xiabin Jing
Biomaterials 2010 31(9) pp: 2646-2654
Publication Date(Web):
DOI:10.1016/j.biomaterials.2009.12.019
Co-reporter:Jun Yue, Xiaoyuan Li, Guojun Mo, Rui Wang, Yubin Huang, and Xiabin Jing
Macromolecules 2010 Volume 43(Issue 23) pp:9645-9654
Publication Date(Web):November 15, 2010
DOI:10.1021/ma101960d
Two kinds of amphiphilic block copolymers, allyoxyl poly(ethylene glycol)-b-poly(l-lactide) and methoxyl poly(ethylene glycol)-b-poly(l-lactide-co-2-methyl-2-allyloxycarbonyl-propylene carbonate), were synthesized in a controllable manner. Radical mediated thiol−ene reaction was utilized to modify these two precursor block copolymers with three model mercaptans. Highly efficient and quantitative modification under UV light without adding any photoinitiators was observed by 1H NMR spectra of the products collected at specific time points. The reaction rate was mainly dependent on molar ratio of thiol to vinyl in feeding. Quantitative transformation of the vinyl groups in both block copolymers was realized in 0.5−2 h when using excessive thiol with respect to vinyl. Using commercially available mercaptans, different functional groups were introduced into the block copolymers, thus realizing modular functionalization of target block copolymers. This method of functionalization effectively avoided traditional protection/deprotection procedures, thus greatly simplifying the process of functionalization. Precipitation and dialysis procedures were proved efficient to eliminate excess mercaptans, thus endowing the material with good biocompatibility.
Co-reporter:Xiuli Hu, Shi Liu, Yubin Huang, Xuesi Chen and Xiabin Jing
Biomacromolecules 2010 Volume 11(Issue 8) pp:
Publication Date(Web):July 7, 2010
DOI:10.1021/bm100458n
Doxorubicin (Dox) was conjugated onto a biodegradable block copolymer methoxy-poly(ethylene glycol)-block-poly(lactide-co-2,2-dihydroxymethylpropylene carbonate (mPEG-b-P(LA-co-DHP)) via a carbamate linkage and an acid-labile hydrazone linkage, respectively. Mutifunctional mixed micelles consisting of Dox-containing copolymer mPEG-b-P(LA-co-DHP/Dox) and folic acid-containing copolymer mPEG-b-P(LA-co-DHP/FA) were successfully prepared by coassembling the two component copolymers. The mixed micelles had well-defined core shell structure and their diameters were in the range of 70−100 nm. Both Dox-conjugates (via carbamate or hydrazone linkage) showed pH-dependent release behavior, and the micelles with hydrazone linkage showed more pH-sensitivity compared to those with carbamate linkage. The in vitro cell uptake experiment by CLSM and flow cytometry showed preferential internalization of FA-containing micelles by human ovarian cancer cell line SKOV-3 than that without FA. Flow cytometric analysis was conducted to reveal the enhanced cell apoptosis caused by the FA-containing micelles. These results suggested that these micelles containing both chemotherapeutic and targeting ligand could be a promising nanocarrier for targeting the drugs to cancer cells and releasing the drug molecules inside the cancer cells.
Co-reporter:Tiancheng Lu;Jing Sun;Xuexi Chen;Peibiao Zhang
Macromolecular Bioscience 2009 Volume 9( Issue 11) pp:1059-1068
Publication Date(Web):
DOI:10.1002/mabi.200900134
Co-reporter:Xiuli Hu;Xuesi Chen;Jizheng Wei;Shi Liu
Macromolecular Bioscience 2009 Volume 9( Issue 5) pp:456-463
Publication Date(Web):
DOI:10.1002/mabi.200800158
Co-reporter:Zhigang Xie;Tiancheng Lu;Xuesi Chen;Yonghui Zheng
Journal of Biomedical Materials Research Part A 2009 Volume 88A( Issue 1) pp:238-245
Publication Date(Web):
DOI:10.1002/jbm.a.31861
Abstract
Docetaxel (DX) is one of the most effective antineoplastic drugs. Its current clinical administration is limited because of its hydrophobicity and serious side effects. A polymer/DX conjugate is designed and successfully prepared to solve these problems. It is monomethoxy-poly(ethylene glycol)-block-poly(L-lactide)/DX (MPEG-PLLA/DX). It was synthesized by reacting DX with carboxyl-terminated copolymer MPEG-PLLA, which was prepared by reacting succinic anhydride with hydroxyl-terminated copolymer monomethoxy-poly(ethylene glycol)-block-poly(L-lactide) (MPEG-PLLA). Its structure and molecular weight was confirmed by 1H NMR and GPC. The MPEG-PLLA/DX micelles in aqueous solution were prepared using a solvent displacement method and characterized by dynamic light scattering for size and size distribution, and by transmission electron microscopy for surface morphology. Its antitumor activity against HeLa cancer cells evaluated by MTT assay showed that it had a similar antitumor activity to pure DX at the same drug content. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Co-reporter:Zhigang Xie;Xiuli Hu;Xuesi Chen;Guojun Mo;Jing Sun
Advanced Engineering Materials 2009 Volume 11( Issue 3) pp:B7-B11
Publication Date(Web):
DOI:10.1002/adem.200800254
Co-reporter:Xiuli Hu;Xuesi Chen;Haibo Cheng
Journal of Polymer Science Part A: Polymer Chemistry 2009 Volume 47( Issue 1) pp:161-169
Publication Date(Web):
DOI:10.1002/pola.23134
Abstract
A functionalized cyclic carbonate monomer containing a cinnamate moiety, 5-methyl-5-cinnamoyloxymethyl-1,3-dioxan-2-one (MC), was prepared for the first time with 1,1,1-tri(hydroxymethyl) ethane as a starting material. Subsequent polymerization of the new cyclic carbonate and its copolymerization with L-lactide (LA) were successfully performed with diethyl zinc (ZnEt2) as initiator/catalyst. NMR was used for microstructure identification of the obtained monomer and copolymers. Differential scanning calorimetry (DSC) was used to characterize the functionalized poly(ester-carbonate). The results indicated that the copolymers displayed a single glass transition temperature (Tg) and the Tg decreased with increasing carbonate content and followed the Fox equation, indicative of a random microstructure of the copolymer. The photo-crosslinking of the cinnamate-carrying copolymer was also demonstrated. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 161–169, 2009
Co-reporter:Jing Sun, Xuesi Chen, Jinshan Guo, Quan Shi, Zhigang Xie, Xiabin Jing
Polymer 2009 50(2) pp: 455-461
Publication Date(Web):
DOI:10.1016/j.polymer.2008.11.015
Co-reporter:Xiaoyi Xu;Tongjun Liu;Shaohui Liu
Journal of Materials Science: Materials in Medicine 2009 Volume 20( Issue 5) pp:1167-1173
Publication Date(Web):2009 May
DOI:10.1007/s10856-008-3672-2
The current study investigates the feasibility of using a biodegradable polymeric stent in common bile duct (CBD) repair and reconstruction. Here, poly(l-lactide-co-glycolide) (PLGA, molar ratio LA/GA = 80/20) was processed into a circular tube- and dumbbell-shaped specimens to determine the in vitro degradation behavior in bile. The morphology, weight loss, and molecular weight changes were then investigated in conjunction with evaluations of the mechanical properties of the specimen. Circular tube-shaped PLGA stents with X-ray opacity were subsequently used in common bile duct exploration (CBDE) and primary suturing in canine models. Next, X-ray images of CBD stents in vivo were compared and levels of serum liver enzymes and a histological analysis were conducted after stent transplantation. The results showed that the PLGA stents exhibited the required biomedical properties and spontaneously disappeared from CBDs in 4–5 weeks. The degradation period and function match the requirements in repair and reconstruction of CBDs to support the duct, guide bile drainage, and reduce T-tube-related complications.
Co-reporter:Jing Sun, Yubin Huang, Quan Shi, Xuesi Chen and Xiabin Jing
Langmuir 2009 Volume 25(Issue 24) pp:13726-13729
Publication Date(Web):May 21, 2009
DOI:10.1021/la901194k
An oxygen carrier was prepared by encapsulating carbonylated hemoglobin (CO-Hb) molecules into polypeptide vesicles made from poly(l-lysine)-block-poly(l-phenylalanine) (PLL-b-PPA) diblock copolymers in aqueous medium at pH 5.8. The encapsulation was confirmed by confocal laser scanning microscopy (CLSM). The morphology and size of the vesicles were studied by field-emission scanning electron microscopy (ESEM). They had a spherical shape with a mean diameter of about 4 to 5 μm. The encapsulation efficiency of hemoglobin was 40 wt %, and the hemoglobin content in the vesicles was 32 wt %. The CO-Hb encapsulated in the PLL-b-PPA vesicles was more stable than free CO-Hb under ambient conditions. In the presence of a O2 atmosphere, the CO-Hb in the vesicle could be converted into oxygen-binding hemoglobin (O2-Hb) under irradiation of visible light for 2 h. Therefore, the CO-Hb/PLL-b-PPA vesicles are expected to be used as red blood cell substitutes.
Co-reporter:Tiancheng Lu, Xuesi Chen, Quan Shi, Yu Wang, Peibiao Zhang, Xiabin Jing
Acta Biomaterialia 2008 Volume 4(Issue 6) pp:1770-1777
Publication Date(Web):November 2008
DOI:10.1016/j.actbio.2008.05.006
Abstract
This paper aims at developing novel bioactive fibrous mats for protein immobilization and for protein separation/purification. For this purpose, an amphiphilic triblock copolymer, biotinylated poly(ethylene glycol)-b-poly(l-lactide)-b-poly(l-lysine) was co-electrospun together with poly(l-lactide-co-glycolide) into ultrafine fibers ∼2 μm in diameter, and a layer of blocking agent was coated on the fiber surfaces to block off possible non-specific binding of proteins. The biotin species retained their ability to specifically recognize and bind streptavidin, and the immobilized streptavidin could further combine with biotinylated antibodies, antigens and other biological moieties. Horseradish peroxidase-labeled streptavidin and fluorescein isothiocyanate-labeled goat globulin were used to detect the immobilizations of streptavidin and rabbit anti-goat IgG(H + L) via enzyme-linked immunoassay and confocal laser scanning microscope, respectively. The immobilized antigen was eluted from the fiber substrate with a glycine/HCl solution and the eluted antigen retained its bioactivity. Therefore, these biotin-carrying composite fibers have a variety of uses, including selective immobilization of functional proteins, antigen/antibody separation and purification, and vaccine preparation.
Co-reporter:Xiaoyi Xu, Tongjun Liu, Kai Zhang, Shaohui Liu, Zhen Shen, Yuxin Li, Xiabin Jing
Polymer Degradation and Stability 2008 Volume 93(Issue 4) pp:811-817
Publication Date(Web):April 2008
DOI:10.1016/j.polymdegradstab.2008.01.022
The objective of this study was to evaluate degradation behavior and the feasibility of biodegradable polymeric stents in common bile duct (CBD) repair and reconstruction. Various molar ratios of lactide (LA) and glycolide (GA) in poly(l-lactide-co-glycolide) (PLGA) were synthesized and processed into a circular tubing of ∼10.0 mm outer diameter and a wall thickness of about 2.0 mm. This tubing was cut into 40.0 mm length to form CBD stents. The stents were placed into human bile to determine the degradation behavior in vitro. The morphology, configuration, mass loss, water uptake, molecular weight and composition changes were examined. The PLGA with LA/GA = 71/29 exhibited an acceptable degradation life and was chosen as an in vivo stent material. These PLGA stents were used in common bile duct exploration (CBDE) and primary suturing for rats. Degradation status of the stents was examined and comparison was made between those before and after surgical procedure. The results showed that the polymer stents exhibited the same biomedical functions as T tubes and spontaneously disappeared from CBD in 4–5 weeks. Therefore, the PLGA stents fits the requirements in repair and reconstruction of CBD, to support the duct, guide bile drainage and reduce T-tube-related complications.
Co-reporter:Lixin Yang, Xuesi Chen, Xiabin Jing
Polymer Degradation and Stability 2008 Volume 93(Issue 10) pp:1923-1929
Publication Date(Web):October 2008
DOI:10.1016/j.polymdegradstab.2008.06.016
Polycarbodiimide (CDI) was used to improve the thermal stability of poly(l-lactic acid) (PLA) during processing. The properties of PLA containing various amounts of CDI were characterized by GPC, DSC, rheology, and tensile tests. The results showed that an addition of CDI in an amount of 0.1–0.7 wt% with respect to PLA led to stabilization of PLA at even 210 °C for up to 30 min, as evidenced by much smaller changes in molecular weight, melt viscosity, and tensile strength and elongation compared to the blank PLA samples. In order to examine the possible stabilization mechanism, CDI was reacted with water, acetic acid, l-lactic acid, ethanol and low molecular weight PLA. The molecular structures of the reaction products were measured with FTIR. The results showed that CDI could react with the residual or newly formed moisture and lactic acid, or carboxyl and hydroxyl end groups in the PLA samples, and thus hamper the thermal degradation and hydrolysis of PLA.
Co-reporter:Zhigang Xie;Xiuli Hu;Xuesi Chen;Tiancheng Lu;Shi Liu
Journal of Applied Polymer Science 2008 Volume 110( Issue 5) pp:
Publication Date(Web):
DOI:10.1002/app.28900
Abstract
A diblcok copolymer monomethoxy poly (ethyleneglycol)-block-poly(L-lactide-co-2-methyl-2-carboxyl-propylene carbonate) (MPEG-b-P(LA-co-MCC)) was obtained by copolymerization of L-lactide (LA) and 2-methyl-2-benzoxycarbonyl-propylene carbonate (MBC) and subsequent catalytic hydrogenation. The pendant carboxyl groups of the copolymer MPEG-b-P(LA-co-MCC) were conjugated with antitumor drug docetaxel and tripeptide arginine-glycine-aspartic acid (RGD), respectively. 1H-NMR spectra confirmed the structure of the copolymer MPEG-b-P(LA-co-MCC/docetaxel) and MPEG-b-P(LA-co-MCC/RGD). In vitro antitumor assay indicates that the MPEG-b-P(LA-co-MCC/docetaxel) conjugate shows high cytotoxic activity against HeLa cancer cells. Cell adhesion and spreading experiment shows that copolymer MPEG-b-P(LA-co-MCC/RGD) is of benefit to cell adherence and is a promising biodegradable material for cell and tissue engineering. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Co-reporter:Jing Sun;Quan Shi;Xuesi Chen;Jinshan Guo
Macromolecular Chemistry and Physics 2008 Volume 209( Issue 11) pp:1129-1136
Publication Date(Web):
DOI:10.1002/macp.200800018
Co-reporter:Jing Sun, Xuesi Chen, Tiancheng Lu, Shi Liu, Huayu Tian, Zhaopei Guo and Xiabin Jing
Langmuir 2008 Volume 24(Issue 18) pp:10099-10106
Publication Date(Web):August 13, 2008
DOI:10.1021/la8013877
A novel biodegradable diblock copolymer, poly(l-cysteine)-b-poly(l-lactide) (PLC-b-PLLA), was synthesized by ring-opening polymerization (ROP) of N-carboxyanhydride of β-benzyloxycarbonyl-l-cysteine (ZLC-NCA) with amino-terminated poly(l-lactide) (NH2-PLLA) as a macroinitiator in a convenient way. The diblock copolymer and its precursor were characterized by 1H NMR, Fourier transform infrared (FT-IR), gel permeation chromatography (GPC), and X-ray photoelectron spectroscopy (XPS) measurements. The length of each block polymer could be tailored by molecular design and the ratios of feeding monomers. The cell adhesion and cell spread on the PZLC-b-PLLA and PLC-b-PLLA films were enhanced compared to those on pure PLA film. PLC-b-PLLA can self-assemble to form micelles in aqueous media. A pyrene probe is used to demonstrate the micelle formation of PLC-b-PLLA in aqueous solution. Due to the ease of disulfide exchange with thiols, the obtained micelles are reversible shell cross-linked (SCL) micelles. The morphology and size of the micelles are studied by dynamic light scattering (DLS) and environmental scanning electron microscopy (ESEM).
Co-reporter:Zhigang Xie, Xiuli Hu, Xuesi Chen, Jing Sun, Quan Shi and Xiabin Jing
Biomacromolecules 2008 Volume 9(Issue 1) pp:
Publication Date(Web):December 8, 2007
DOI:10.1021/bm700906k
Novel biodegradable poly(carbonate ester)s with photolabile protecting groups were synthesized by ring-opening copolymerization of l-lactide (LA) with 5-methyl-5-(2-nitro-benzoxycarbonyl)-1,3-dioxan-2-one (MNC) with diethyl zinc (Et2Zn) as catalyst. The poly(l-lactide-co-5-methyl-5-carboxyl-1,3-dioxan-2-one) (P(LA-co-MCC)) was obtained by UV irradiation of poly(l-lactide acid-co-5-methyl-5-(2-nitro-benzoxycarbonyl)-1,3-dioxan-2-one) (P(LA-co-MNC)) to remove the protective 2-nitrobenzyl group. The free carboxyl groups on the copolymers P(LA-co-MCC) were reacted with paclitaxel, a common antitumor drug. Gel permeation chromatography and NMR studies confirmed the copolymer structures and successful attachment of paclitaxel to the copolymer.
Co-reporter:Xiuli Hu, Shi Liu, Xuesi Chen, Guojun Mo, Zhigang Xie and Xiabin Jing
Biomacromolecules 2008 Volume 9(Issue 2) pp:
Publication Date(Web):January 22, 2008
DOI:10.1021/bm701092j
A new biodegradable amphiphilic block copolymer, poly(ethylene glycol)-b-poly(l-lactide-co-9-phenyl-2,4,8,10-tetraoxaspiro[5,5]undecan-3-one) [PEG-b-P(LA-co-PTO)], was successfully prepared by ring-opening polymerization (ROP) of l-lactide (LA) and functionalized carbonate monomer 9-phenyl-2,4,8,10-tetraozaspiro[5,5]undecan-3-one (PTO) in the presence of monohydroxyl poly(ethylene glycol) as macroinitiator using Sn(Oct)2 as catalyst. NMR, FT-IR, and GPC studies confirmed the copolymer structure. It could self-assemble into micelles in aqueous solution with critical micelle concentration (CMC) in the magnitude of mg/L, which changed with the composition of the copolymer. After catalytic hydrogenation, copolymers with active hydroxyl groups were obtained. Adhesion and proliferation of Vero cells on the copolymer films showed that the synthesized copolymers were good biocompatible materials. In vitro degradation of the copolymer before and after deprotection was investigated in the presence of proteinase K. The free hydroxyl groups on the copolymers were capable of further modification with biotin. This new amphiphilic block copolymer has great potential for both drug encapsulation and conjugate because of its low CMC and the presence of active hydroxyl groups.
Co-reporter:Xiuli Hu;Xuesi Chen;Shi Liu;Quan Shi
Journal of Polymer Science Part A: Polymer Chemistry 2008 Volume 46( Issue 5) pp:1852-1861
Publication Date(Web):
DOI:10.1002/pola.22530
Abstract
A series of novel poly(ester-carbonate)s bearing pendant allyl ester groups P(LA-co-MAC)s were prepared by ring-opening copolymerization of L-lactide (LA) and 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) with diethyl zinc (ZnEt2) as initiator. NMR analysis investigated the microstructure of the copolymer. DSC results indicated that the copolymers displayed a single glass-transition temperature (Tg), which was indicative of a random copolymer, and the Tg decreased with increasing carbonate content in the copolymer. Then NHS-activated folic acid (FA) first reacted with 2-aminoethanethiol to yield FA-SH; grafting FA-SH to P(LA-co-MAC) in the presence of TEA produced P(LA-co-MAC)/FA. The structure of P(LA-co-MAC)/FA and its precursor were confirmed by 1H NMR and XPS analysis. Cell experiments showed that FA-grafted P(LA-co-MAC) had improved adhesion and proliferation behavior of vero cells on the polymer films. Therefore, the novel FA-grafted block copolymer is expected to find application in drug delivery or tissue engineering. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1852–1861, 2008
Co-reporter:Xiuli Hu;Xuesi Chen;Zhigang Xie;Haibo Cheng
Journal of Polymer Science Part A: Polymer Chemistry 2008 Volume 46( Issue 21) pp:7022-7032
Publication Date(Web):
DOI:10.1002/pola.23008
Abstract
This article deals with (1) synthesis of novel cyclic carbonate monomer (2-oxo [1,3]dioxan-5-yl)carbamic acid benzyl ester (CAB) containing protected amino groups; (2) ring-opening copolymerization of the cyclic monomer with L-lactide (LA) to provide novel degradable poly(ester-carbonate)s with functional groups; (3) removal of the protective benzyloxycarbonyl (Cbz) groups by catalytic hydrogenation to afford the corresponding poly(ester-co-carbonate)s with free amino groups; (4) grafting of oligopeptide Gly-Arg-Gly-Asp-Ser-Tyr (GRGDSY, abbreviated as RGD) onto the copolymer pendant amino groups in the presence of 1,1′-carbonyldiimidazole (CDI). The structures of P(LA-co-CA/RGD) and its precursor were confirmed by 1H NMR analysis. Cell experiments showed that P(LA-co-CA/RGD) had improved adhesion and proliferation behavior. Therefore, the novel RGD-grafted block copolymer is promising for cell or tissue engineering applications. © Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7022–7032, 2008
Co-reporter:Zhigang Xie, Huili Guan, Xuesi Chen, Changhai Lu, Li Chen, Xiuli Hu, Quan Shi, Xiabin Jing
Journal of Controlled Release 2007 Volume 117(Issue 2) pp:210-216
Publication Date(Web):12 February 2007
DOI:10.1016/j.jconrel.2006.11.014
A novel amphiphilic polymer–paclitaxel conjugate P(LGG-paclitaxel)-PEG-P(LGG-paclitaxel) has been prepared. It was derived from its parent polymer P(LGG)-PEG-P(LGG), poly{(lactic acid)-co-[(glycolic acid)-alt-(l-glutamic acid)]}-block-poly(ethylene glycol)-block-poly{(lactic acid)-co-[(glycolic acid)-alt-(l-glutamic acid)]}, which was prepared by ring-opening copolymerization of l-lactide (LLA) with (3s)-benzoxylcarbonylethyl-morpholine-2,5-dione (BEMD) in the presence of dihydroxyl PEG with molecular weight of 4600 as a macroinitiator using stannous octoate (Sn(Oct)2) as catalyst, and by subsequent catalytic hydrogenation. It could self-assemble into micelles in an aqueous system with P(LGG-paclitaxel) block in the core and PEG in the shell. ESEM and DLS analysis of the micelles revealed a homogeneous spherical morphology and a unimodal size distribution. In vitro release of paclitaxel from the conjugate micelles showed that its release rate depended on pH value and was higher at lower pH than in neutral condition. In vitro antitumor activity of the paclitaxel conjugate against rat brain glioma C6 cells was evaluated by MTT method. The results showed that the paclitaxel can be released from the conjugate without losing cytotoxicity.
Co-reporter:Xiuling Xu, Xuesi Chen, Aixue Liu, Zhongkui Hong, Xiabin Jing
European Polymer Journal 2007 Volume 43(Issue 8) pp:3187-3196
Publication Date(Web):August 2007
DOI:10.1016/j.eurpolymj.2007.05.024
Composite fibers composed of poly(l-lactide)-grafted hydroxyapatite (PLA-g-HAP) nanoparticles and polylactide (PLA) matrix were prepared by electro-spinning. Environmental scanning electron microscope (ESEM) and transmission electron microscopy (TEM) were employed to investigate the morphology of the composite fibers and the distribution of PLA-g-HAP nanoparticles in the fibers, respectively. At a low content (∼4 wt%) of PLA-g-HAP, the nanoparticles dispersed uniformly in the fibers and the composite fibrous mats exhibited higher strength properties, compared with the pristine PLA fiber mats and the simple hydroxyapatite/PLA blend fiber mats. But when the content of PLA-g-HAP further increased, the nanoparticles began to aggregate, which resulted in the deterioration of the mechanical properties of the composite fiber mats. The degradation behaviors of the composite fiber mats were closely related to the content of PLA-g-HAP. At a low PLA-g-HAP content, degradation may be delayed due to the reduction of autocatalytic degradation of PLA. When PLA-g-HAP content was high, degradation rate increased because of the enhanced wettability of the composite fibers and the escape of the nanoparticles from fiber surfaces during incubation.
Co-reporter:Zhigang Xie, Changhai Lu, Xuesi Chen, Li Chen, Xiuli Hu, Quan Shi, Xiabin Jing
European Polymer Journal 2007 Volume 43(Issue 5) pp:2080-2087
Publication Date(Web):May 2007
DOI:10.1016/j.eurpolymj.2007.03.001
A novel biodegradable poly(ε-caprolactone)-poly(ethylene glycol)-based polyurethanes (PCL-PEG-PU) with pendant amino groups was synthesized by direct coupling of PEG ester of NH2-protected-(aspartic acid) (PEG-Asp-PEG diols) and poly(ε-caprolactone) (PCL) diols with hexamethylene dissocyanate (HDI) under mild reaction conditions and by subsequent deprotection of benzyloxycarbonyl (Cbz) groups. GPC, 1H NMR, and 13C NMR studies confirmed the polymer structures and the complete deprotection. DSC and WXRD results indicated that the crystallinity of the copolymer was enhanced with increasing PCL diols in the copolymer. The content of amino group in the polymer could be adjusted by changing the molar ratio of PEG-Asp-PEG diols to PCL diols. Thus the results of this study provide a good way to prepare polyurethanes bearing hydrophilic PEG segments and reactive amino groups without complicated synthesis.
Co-reporter:Zhigang Xie;Tiancheng Lu;Xuesi Chen;Changhai Lu;Yonghui Zheng
Journal of Applied Polymer Science 2007 Volume 105(Issue 4) pp:2271-2279
Publication Date(Web):26 APR 2007
DOI:10.1002/app.26236
A triblock poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid) (PLA–PEG–PLA)/paclitaxel (PTX) conjugate was synthesized by the reaction of carboxyl-terminated copolymer PLA–PEG–PLA with PTX in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. Carboxyl-terminated copolymer PLA–PEG–PLA was prepared by the reaction of the hydroxyl end groups in copolymer PLA–PEG–PLA with succinic anhydride. Its structure was confirmed by NMR and gel permeation chromatography. The PLA–PEG–PLA/PTX conjugates could self-assemble into micelles in aqueous solutions with a low critical micelle concentration. Dynamic light scattering and environmental scanning electron microscopy analyses of the PLA–PEG–PLA/PTX micelles revealed their spherical structure and size of 220 nm. The antitumor activity of the conjugate against woman Hela cancer cells, evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method, showed that the conjugates had an antitumor activity similar to that of pure PTX. The obtained PLA–PEG–PLA/PTX conjugates are expected to be used in clinical practice. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Co-reporter:Xiaoyi Xu;Haijun Yu;Xuesi Chen;Tiancheng Lu;Peibiao Zhang
Journal of Applied Polymer Science 2007 Volume 103(Issue 1) pp:125-133
Publication Date(Web):23 OCT 2006
DOI:10.1002/app.24835
The poly(vinyl alcohol)/poly(N-vinyl pyrrolidone) (PVA–PVP) hydrogels containing silver nanoparticles were prepared by repeated freezing–thawing treatment. The silver content in the solid composition was in the range of 0.1–1.0 wt %, the silver particle size was from 20 to 100 nm, and the weight ratio of PVA to PVP was 70 : 30. The influence of silver nanoparticles on the properties of PVA–PVP matrix was investigated by differential scanning calorimeter, infrared spectroscopy and UV–vis spectroscopy, using PVA–PVP films containing silver particles as a model. The morphology of freeze-dried PVA–PVP hydrogel matrix and dispersion of the silver nanoparticles in the matrix was examined by scanning electron microscopy. It was found that a three-dimensional structure was formed during the process of freezing–thawing treatment and no serious aggregation of the silver nanoparticles occurred. Water absorption properties, release of silver ions from the hydrogels and the antibacterial effects of the hydrogels against Escherichia coli and Staphylococcus aureus were examined too. It was proved that the nanosilver-containing hydrogels had an excellent antibacterial ability. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 125–133, 2007
Co-reporter:Wenshou Wang;Peng Ping;Xuesi Chen
Journal of Applied Polymer Science 2007 Volume 104(Issue 6) pp:4182-4187
Publication Date(Web):27 MAR 2007
DOI:10.1002/app.26039
A series of biodegradable polyurethanes (PUs) are synthesized from the copolymer diols prepared from L-lactide and ε-caprolactone (CL), 2,4-toluene diisocyanate, and 1,4-butanediol. Their thermal and mechanical properties are characterized via FTIR, DSC, and tensile tests. Their Tgs are in the range of 28–53°C. They have high modulus, tensile strength, and elongation ratio at break. With increasing CL content, the PU changes from semicrystalline to completely amorphous. Thermal mechanical analysis is used to determine their shape-memory property. When they are deformed and fixed at proper temperatures, their shape-recovery is almost complete for a tensile elongation of 150% or a compression of 2-folds. By changing the content of CL and the hard-to-soft ratio, their Tgs and their shape-recovery temperature can be adjusted. Therefore, they may find wide applications. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 4182–4187, 2007
Co-reporter:Wenshou Wang;Peng Ping;Xuesi Chen
Polymer International 2007 Volume 56(Issue 7) pp:
Publication Date(Web):18 APR 2007
DOI:10.1002/pi.2204
A series of biodegradable polylactide-based polyurethanes (PLAUs) were synthesized using PLA diol (Mn = 3200) as soft segment, 4,4′-diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate (TDI), and isophorone diisocyanate (IPDI) as hard segment, and 1,4-butanediol as chain extender. The structures and properties of these PLAUs were studied using infrared spectroscopy, differential scanning calorimetry, tensile testing, and thermomechanical analysis. Among them, the MDI-based PLAU has the highest Tg, maximum tensile strength, and restoration force, the TDI-based PLAU has the lowest Tg, and the IPDI-based PLAU has the highest tensile modulus and elongation at break. They are all amorphous. The shape recovery of the three PLAUs is almost complete in a tensile elongation of 150% or a twofold compression. They can keep their temporary shape easily at room temperature (20 °C). More importantly, they can deform and recover at a temperature below their Tg values. Therefore, by selecting the appropriate hard segment and adjusting the ratio of hard to soft segments, they can meet different practical demands for shape memory medical devices. Copyright © 2007 Society of Chemical Industry
Co-reporter:Zhigang Xie;Changhai Lu;Xuesi Chen;Yu Wang;Li Chen;Xiuli Hu;Quan Shi
Journal of Polymer Science Part A: Polymer Chemistry 2007 Volume 45(Issue 9) pp:1737-1745
Publication Date(Web):20 MAR 2007
DOI:10.1002/pola.21941
Novel poly(ester carbonate)s were synthesized by the ring-opening polymerization of L-lactide and functionalized carbonate monomer 9-phenyl-2,4,8,10-tetraoxaspiro[5,5]undecan-3-one derived from pentaerythritol with diethyl zinc as an initiator. 1H NMR analysis revealed that the carbonate content in the copolymer was almost equal to that in the feed. DSC results indicated that Tg of the copolymer increased with increasing carbonate content in the copolymer. Moreover, the protecting benzylidene groups in the copolymer poly(L-lactide-co-9-phenyl-2,4,8,10-tetraoxaspiro[5,5]undecan-3-one) were removed by hydrogenation with palladium hydroxide on activated charcoal as a catalyst to give a functional copolymer, poly(L-lactide-co-2,2-dihydroxylmethyl-propylene carbonate), containing pendant primary hydroxyl groups. Complete deprotection was confirmed by 1H NMR and FTIR spectroscopy. The in vitro degradation rate of the deprotected copolymers was faster than that of the protected copolymers in the presence of proteinase K. The cell morphology and viability on a copolymer film evaluated with ECV-304 cells showed that poly(ester carbonate)s derived from pentaerythritol are good biocompatible materials suitable for biomedical applications. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45:1737 –1745, 2007
Co-reporter:Peng Ping;Wenshou Wang;Peibiao Zhang;Xuesi Chen
Frontiers of Chemistry in China 2007 Volume 2( Issue 4) pp:331-336
Publication Date(Web):2007 October
DOI:10.1007/s11458-007-0063-z
A series of segmented poly(L-lactide)-polyurethanes (PLA-PUs) were synthesized by a two-step method, with oligo-poly(L-lactide) (PLA) as the soft segments and the reaction product of 2,4-toluene diisocyanate (TDI) and ethylene glycol (EG) as the hard segments. The shape-memory properties and biocompatibility of PLA-PUs were examined. The 50% compressed PLA-PUs could recover almost 100% to their original shape within 10°C from the lowest recovery temperature (22°C–37°C). In the recovery process the PLA-PU showed a maximum contracting stress in the range of 1.5–4 MPa. Cell incubation experiments show that PLA-PU has biocompatibility comparable to that of pure PLA. Therefore, this kind of polyurethane can be used for implanted medical devices with shape memory requirements.
Co-reporter:Xuesi Chen;Xiuli Hu;Zhigang Xie;Shi Liu
Journal of Polymer Science Part A: Polymer Chemistry 2007 Volume 45(Issue 23) pp:5518-5528
Publication Date(Web):19 OCT 2007
DOI:10.1002/pola.22297
The synthesis of a new cyclic carbonate monomer containing an allyl group was reported and its biodegradable amphiphilic block copolymer, poly(ethylene glycol)-block-poly(L-lactide-co-5-methyl-5-allyloxycarbonyl-propylene carbonate) [PEG-b-P(LA-co-MAC)] was synthesized by ring-opening polymerization (ROP) of L-lactide (LA) and 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) in the presence of poly (ethylene glycol) as a macroinitiator, with diethyl zinc as a catalyst. 13C NMR and 1H NMR were used for microstructure identification of the copolymers. The copolymer could form micelles in aqueous solution. The core of the micelles is built of the hydrophobic P(LA-co-MAC) chains, whereas the shell is set up by the hydrophilic PEG blocks. The micelles exhibited a homogeneous spherical morphology and unimodal size distribution. By using the cyclic carbonate monomer containing allyl side-groups, crosslinking of the PEG-b-P(LA-co-MAC) inner core was possible. The adhesion and spreading of ECV-304 cells on the copolymer were better than that on PLA films. Therefore, this biodegradable amphiphilic block copolymer is expected to be used as a biomaterial for drug delivery and tissue engineering. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5518–5528, 2007
Co-reporter:Peng Ping;Wenshou Wang;Xuesi Chen
Journal of Polymer Science Part B: Polymer Physics 2007 Volume 45(Issue 5) pp:557-570
Publication Date(Web):23 JAN 2007
DOI:10.1002/polb.20974
Poly(ε-caprolactone)-based segmented polyurethanes (PCLUs) were prepared from poly(ε-caprolactone) diol, diisocyanates (DI), and 1,4-butanediol. The DIs used were 4,4′-diphenylmethane diisocyanate (MDI), 2,4-toluenediisocyanate (TDI), isophorone diisocyanate (IPDI), and hexamethylene diisocyanate (HDI). Differential scanning calorimetry, small-angle X-ray scattering, and dynamic mechanical analysis were employed to characterize the two-phase structures of all PCLUs. It was found that HDI- and MDI-based PCLUs had higher degree of microphase separation than did IPDI- and TDI-based PCLUs, which was primarily due to the crystallization of HDI- and MDI-based hard-segments. As a result, the HDI-based PCLU exhibited the highest recovery force up to 6 MPa and slowest stress relaxation with increasing temperature. Besides, it was found that the partial damage in hard-segment domains during the sample deformation was responsible for the incomplete shape-recovery of PCLUs after the first deformation, but the damage did not develop during the subsequent deformation. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 557–570, 2007
Co-reporter:Quan Shi;Xuesi Chen;Changhai Lu;Zhigang Xie;Xiuli Hu;Tiancheng Lu;Jia Ma
Journal of Polymer Science Part A: Polymer Chemistry 2007 Volume 45(Issue 15) pp:3204-3217
Publication Date(Web):11 JUN 2007
DOI:10.1002/pola.22070
A novel biodegradable aliphatic poly(L-lactide-co-carbonate) bearing pendant acetylene groups was successfully prepared by ring-opening copolymerization of L-lactide (LA) with 5-methyl-5-propargyloxycarbonyl-1,3-dioxan-2-one (PC) in the presence of benzyl alcohol as initiator with ZnEt2 as catalyst in bulk at 100 °C and subsequently used for grafting 2-azidoethyl β-D-glucopyranoside and 2-azidoethyl β-lactoside by the typical “click reaction,” that is Cu(I)-catalyzed cycloaddition of azide and alkyne. The density of acetylene groups in the copolymer can be tailored by the molar ratio of PC to LA during the copolymerization. The aliphatic copolymers grafted with sugars showed low cytotoxicity to L929 cells, improved hydrophilic properties and specific recognition and binding ability with lectins, that is Concanavalin A (Con A) and Ricinus communis agglutinin (RCA). Therefore, this kind of sugar-grafted copolymer could be a good candidate in variety of biomedical applications. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3204 –3217, 2007
Co-reporter:Xiuling Xu;Xinri Wang;Xuesi Chen;Lixin Yang;Xiuli Zhuang
Macromolecular Rapid Communications 2006 Volume 27(Issue 19) pp:1637-1642
Publication Date(Web):27 SEP 2006
DOI:10.1002/marc.200600384
Summary: Uniform core-sheath nanofibers are prepared by electrospinning a water-in-oil emulsion in which the aqueous phase consists of a poly(ethylene oxide) (PEO) solution in water and the oily phase is a chloroform solution of an amphiphilic poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLA) diblock copolymer. The obtained fibers are composed of a PEO core and a PEG-PLA sheath with a sharp boundary in between. By adjusting the emulsion composition and the emulsification parameters, the overall fiber size and the relative diameters of the core and the sheath can be changed. A mechanism is proposed to explain the process of transformation from the emulsion to the core-sheath fibers, i.e., the stretching and evaporation induced de-emulsification. In principle, this process can be applied to other systems to prepare core-sheath fibers in place of concentric electrospinning and it is especially suitable for fabricating composite nanofibers that contain water-soluble drugs.
Co-reporter:Wenshou Wang, Peng Ping, Xuesi Chen, Xiabin Jing
European Polymer Journal 2006 Volume 42(Issue 6) pp:1240-1249
Publication Date(Web):June 2006
DOI:10.1016/j.eurpolymj.2005.11.029
A series of polylactide polyurethanes (PLAUs) were synthesized from poly(l-lactide) diols, hexamethylene diisocyanate (HDI), and 1,4-butanediol (BDO). Their thermal and mechanical properties and shape-memory behavior were studied by infrared spectroscopy (IR), differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD), tensile testing, and thermal mechanical analysis (TMA). The Tgs of these polymers were in the range of 33–53 °C, and influenced by the Mn of the PLA diol and the ratio of the soft-segment to the hard-segment. These materials can restore their shapes almost completely after 150% elongation or twofold compression. By changing the Mn of the PLA diol and the ratio of the hard-to-soft-segment, their Tgs and shape-recovery temperatures can be adjusted to the neighborhood of the body temperature. Therefore, these PLAUs are expected to find practical medical applications.
Co-reporter:Xiaoyi Xu, Qingbiao Yang, Yongzhi Wang, Haijun Yu, Xuesi Chen, Xiabin Jing
European Polymer Journal 2006 Volume 42(Issue 9) pp:2081-2087
Publication Date(Web):September 2006
DOI:10.1016/j.eurpolymj.2006.03.032
Biodegradable poly(l-lactide) (PLA) ultrafine fibers containing nanosilver particles were prepared via electrospinning. Morphology of the Ag/PLA fibers and distribution of the silver nanoparticles were characterized. The release of silver ions from the Ag/PLA fibers and their antibacterial activities were investigated. These fibers showed antibacterial activities (microorganism reduction) of 98.5% and 94.2% against Staphylococcus aureus and Escherichia coli, respectively, because of the presence of the silver nanoparticles.
Co-reporter:Haijun Yu;Xuesi Chen;Xiaoyi Xu;Jingquan Hao
Journal of Applied Polymer Science 2006 Volume 101(Issue 4) pp:2453-2463
Publication Date(Web):27 MAY 2006
DOI:10.1002/app.23344
Poly(vinyl alcohol)/poly(N-vinyl pyrrolidone) (PVP)/chitosan hydrogels were prepared by a low-temperature treatment and subsequent 60Co γ-ray irradiation and then were medicated with ciprofloxacin lactate (an antibiotic) and chitosan oligomer (molecular weight = 3000 g/mol). The gel content, swelling ratio, tensile strength, and crystallinity of the hydrogels were determined. The effects of the chitosan molecular weight, the low-temperature treatment procedure, and the radiation dosage on the hydrogel properties were examined. The molecular weight of chitosan was lowered by the irradiation, but its basic polysaccharide structure was not destroyed. Repeating the low-temperature treatment and γ-ray irradiation caused effective physical crosslinking and chemical crosslinking, respectively, and contributed to the mechanical strength of the final hydrogels. The incorporation of PVP and chitosan resulted in a significant improvement in the equilibrium swelling ratio and elongation ratio of the prepared hydrogels. The ciprofloxacin lactate and chitosan oligomer were soaked into the hydrogels. Their in vitro release behaviors were examined, and they were found to follow diffusion-controlled kinetics. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2453–2463, 2006
Co-reporter:Longhai Piao;Jingru Sun;Zhiyuan Zhong;Qizhi Liang;Xuesi Chen;Jung-Hyun Kim
Journal of Applied Polymer Science 2006 Volume 102(Issue 3) pp:2654-2660
Publication Date(Web):23 AUG 2006
DOI:10.1002/app.24058
The quasiliving characteristics of the ring-opening polymerization of ϵ-caprolactone (CL) catalyzed by an organic amino calcium were demonstrated. Taking advantage of this feature, we synthesized a series of poly(ϵ-caprolactone) (PCL)–poly(L-lactide) (PLA) diblock copolymers with the sequential addition of the monomers CL and L-lactide. The block structure was confirmed by 1H-NMR, 13C-NMR, and gel permeation chromatography analysis. The crystalline structure of the copolymers was investigated by differential scanning calorimetry and wide-angle X-ray diffraction analysis. When the molecular weight of the PLA block was high enough, phase separation took place in the block copolymer to form PCL and PLA domains, respectively. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 2654–2660, 2006
Co-reporter:Wenshou Wang;Peng Ping;Haijun Yu;Xuesi Chen
Journal of Polymer Science Part A: Polymer Chemistry 2006 Volume 44(Issue 19) pp:5505-5512
Publication Date(Web):21 AUG 2006
DOI:10.1002/pola.21643
A series of biodegradable, thermoplastic polyurethane elastomers poly(ϵ-caprolactone-co-lactide(polyurethane [PCLA–PU] were synthesized from a random copolymer of L-lactide (LA) and ϵ-caprolactone (CL), hexamethylene diisocyanate, and 1,4-butanediol. The effects of the LA/CL monomer ratio and hard-segment content on the thermal and mechanical properties of PCLA–PUs were investigated. Gel permeation chromatography, IR, 13C NMR, and X-ray diffraction were used to confirm the formation and structure of PCLA–PUs. Through differential scanning calorimetry, tensile testing, and tensile-recovery testing, their thermal and mechanical properties were characterized. Their glass-transition temperatures were below −8 °C, and their soft domains became amorphous as the LA content increased. They displayed excellent mechanical properties, such as a tensile strength as high as 38 MPa, a tensile modulus as low as 10 MPa, and an elongation at break of 1300%. Therefore, they could find applications in biomedical fields, such as soft-tissue engineering and artificial skin. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5505–5512, 2006
Co-reporter:Haijun Yu;Wenshou Wang;Xuesi Chen;Chao Deng
Biopolymers 2006 Volume 83(Issue 3) pp:
Publication Date(Web):7 JUN 2006
DOI:10.1002/bip.20551
A novel synthetic approach to biodegradable amphiphilic copolymers based on poly (ϵ-caprolactone) (PCL) and chitosan was presented, and the prepared copolymers were used to prepare nanoparticles successfully. The PCL-graft-chitosan copolymers were synthesized by coupling the hydroxyl end-groups on preformed PCL chains and the amino groups present on 6-O-triphenylmethyl chitosan and by removing the protective 6-O-triphenylmethyl groups in acidic aqueous solution. The PCL content in the copolymers can be controlled in the range of 10-90 wt %. The graft copolymers were thoroughly characterized by 1H NMR, 13C NMR, FT-IR and DSC. The nanoparticles made from the graft copolymers were investigated by 1H NMR, DLS, AFM and SEM measurements. It was found that the copolymers could form spherical or elliptic nanoparticles in water. The amount of available primary amines on the surface of the prepared nanoparticles was evaluated by ninhydrin assay, and it can be controlled by the grafting degree of PCL. © 2006 Wiley Periodicals, Inc. Biopolymers 83:233–242, 2006
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Co-reporter:Jing Zeng, Lixin Yang, Qizhi Liang, Xuefei Zhang, Huili Guan, Xiuling Xu, Xuesi Chen, Xiabin Jing
Journal of Controlled Release 2005 Volume 105(1–2) pp:43-51
Publication Date(Web):20 June 2005
DOI:10.1016/j.jconrel.2005.02.024
The electrospun fiber mat for drug delivery is a novel formulation with promising clinical applications in the future. The influence of the solubility and compatibility of drugs in the drug/polymer/solvent system on the encapsulation of the drug inside the poly(l-lactide) (PLLA) electrospun fibers and the release behavior of this formulation were examined by using paclitaxel, doxorubicin hydrochloride and doxorubicin base as model drugs. The burst release of the drugs can be avoided by using compatible drugs with polymers, and the drug release can follow nearly zero-order kinetics due to the degradation of the PLLA fibers in the presence of proteinase K.
Co-reporter:Xiuling Xu, Lixin Yang, Xiaoyi Xu, Xin Wang, Xuesi Chen, Qizhi Liang, Jing Zeng, Xiabin Jing
Journal of Controlled Release 2005 Volume 108(Issue 1) pp:33-42
Publication Date(Web):2 November 2005
DOI:10.1016/j.jconrel.2005.07.021
Ultrafine fibers containing water-soluble drugs were successfully electrospun from water-in-oil (W/O) emulsions, in which the aqueous phase contained the water-soluble drugs and the oily phase was a chloroform solution of amphiphilic poly (ethylene glycol)-poly (l-lactic acid) (PEG-PLLA) diblock copolymer. The diameter of the electrospun fibers was in the range of 300 nm–1 μm. A water-soluble anticancer agent, doxorubicin hydrochloride (Dox), was used as the model drug. Its content in the fibers was 1–5 wt.% and it was entirely encapsulated inside the electrospun fibers. Its release from the fibers was controlled by the combined diffusion mechanism and enzymatic degradation mechanism. At the early stage, the diffusion mechanism was predominant and a certain time later, the enzymatic degradation mechanism became predominant. The antitumor activity of the Dox incorporated in the PEG-PLLA fibers against mice glioma cells (C6 cell lines) was evaluated by MTT method. The results showed that the Dox could be released from the fibers without losing cytotoxicity.
Co-reporter:Hui-Li Guan;Xiao-Yi Xu;Chao Deng;Qi-Zhi Liang;Xia-Bin Jing;Xue-Si Chen
Journal of Polymer Science Part A: Polymer Chemistry 2005 Volume 43(Issue 5) pp:1144-1149
Publication Date(Web):26 JAN 2005
DOI:10.1002/pola.20590
Novel poly(ester amide)s containing functional groups were prepared by polycondensation of diamine, diol, and sebacoyl dichloride. Benzyl-protected dimethylolpropionic acid was selected as the diol unit and the diamine was derived from hexanediol and glycine.
Co-reporter:Xuefei Zhang, Yuxin Li, Xuesi Chen, Xiuhong Wang, Xiaoyi Xu, Qizhi Liang, Junli Hu, Xiabin Jing
Biomaterials 2005 Volume 26(Issue 14) pp:2121-2128
Publication Date(Web):May 2005
DOI:10.1016/j.biomaterials.2004.06.024
A paclitaxel/MPEG-PLA block copolymer conjugate was prepared in three steps: (1) hydroxyl-terminated diblock copolymer of monomethoxy-poly(ethylene glycol)-b-poly(lactide) (MPEG-PLA) was synthesized by ring-opening polymerization of l-lactide using MPEG as a maroinitiator; (2) it was converted to carboxyl-terminated MPEG-PLA by reacting with mono-t-butyl ester of diglycolic acid and subsequent deprotecting the t-butyl group with TFA; (3) the latter was reacted with paclitaxel in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. Structures of the polymers synthesized were confirmed by 1H NMR, and their molecular weights were determined by gel permeation chromatography. The antitumor activity of the conjugate against human liver cancer H7402 cells was evaluated by MTT method. The results showed that paclitaxel can be released from the conjugate without losing cytotoxicity.
Co-reporter:Xuesi Chen;Xiuling Xu;Jing Zeng;Qizhi Liang
Macromolecular Bioscience 2004 Volume 4(Issue 12) pp:1118-1125
Publication Date(Web):7 DEC 2004
DOI:10.1002/mabi.200400092
Summary: Poly(L-lactide) (PLLA) and poly(ε-caprolactone) (PCL) ultrafine fibers were prepared by electrospinning. The influence of cationic and anionic surfactants on their enzymatic degradation behavior was investigated by measuring weight loss, molecular weight, crystallinity, and melting temperature of the fibers as a function of degradation time. Under the catalysis of proteinase K, the PLLA fibers containing the anionic surfactant sodium docecyl sulfate (SDS) exhibited a faster degradation rate than those containing cationic surfactant triethylbenzylammonium chloride (TEBAC), indicating that surface electric charge on the fibers is a critical factor for an enzymatic degradation. Similarly, TEBAC-containing PCL fibers exhibited a 47% weight loss within 8.5 h whereas SDS-containing PCL fibers showed little degradation in the presence of lipase PS. By analyzing the charge status of proteinase K and lipase PS under the experimental conditions, the importance of the surface charges of the fibers and their interactions with the charges on the enzymes were revealed. Consequently, a “two-step” degradation mechanism was proposed: (1) the enzyme approaches the fiber surface; (2) the enzyme initiates hydrolysis of the polymer. By means of differential scanning calorimetry and wide-angle X-ray diffraction, the crystallinity and orientation changes in the PLLA and PCL fibers during the enzymatic degradation were investigated, respectively.
Co-reporter:Guojun Mo, Xiuli Hu, Shi Liu, Jun Yue, Rui Wang, Yubin Huang, Xiabin Jing
European Journal of Pharmaceutical Sciences (15 August 2012) Volume 46(Issue 5) pp:329-335
Publication Date(Web):15 August 2012
DOI:10.1016/j.ejps.2012.02.013
Pirarubicin (THP) was conjugated onto the pendant carboxyl groups of poly(ethylene glycol)-block-poly(l-lactide-co-2-methyl-2-carboxyl-propylene carbonate) [PEG-b-P(LA-co-MCC)] through hydrazone, ester, and amide bonds, respectively, and the conjugates were assembled into micelles with diameters between 30 and 60 nm. The in vitro THP release of the three conjugate micelles was conducted in pH 7.4 and 5.0 buffer solutions, and conjugate micelles with hydrazone linkage had the fastest THP release rate. Their in vitro cytotoxicity was tested using mouse mammary adenocarcinoma EMT6 cells and in vivo anti-tumor activity in Balb/c mice models bearing EMT6 tumors were compared with free THP and with each other. The results showed that the polymer–THP conjugates displayed higher cell-uptakes and better anti-tumor activities than free THP at 4 h, and among the three micelles, those with hydrazone linkage had the highest anti-tumor activity in vivo, while those with amide linkage were the lowest.Download high-res image (81KB)Download full-size image
Co-reporter:Wenliang Li, Wenjing Zhang, Xiaoqing Dong, Lesan Yan, Ruogu Qi, Weicai Wang, Zhigang Xie and Xiabin Jing
Journal of Materials Chemistry A 2012 - vol. 22(Issue 34) pp:NaN17448-17448
Publication Date(Web):2012/07/16
DOI:10.1039/C2JM32778C
A porous heterogeneous photocatalyst was prepared by high internal phase emulsion (HIPE) polymerization. Such porous materials have interconnected pores and enough active moieties for photocatalysis. The material demonstrated a very high catalytic efficiency and can be reused for photocatalyzed oxidation of thioanisole under visible light.
Co-reporter:Haihua Xiao, Lesan Yan, Yu Zhang, Ruogu Qi, Wenliang Li, Rui Wang, Shi Liu, Yubin Huang, Yuxin Li and Xiabin Jing
Chemical Communications 2012 - vol. 48(Issue 87) pp:NaN10732-10732
Publication Date(Web):2012/09/26
DOI:10.1039/C2CC34297A
A multifunctional hybrid platinum(IV) prodrug, which consists of both the mitochondria-targeting drug DCA and the DNA-crosslinking drug cisplatin, was synthesized and tethered to a carrier polymer to further self-assemble into micelles for intracellular delivery.
Co-reporter:Jun Yue, Shi Liu, Zhigang Xie, Ying Xing and Xiabin Jing
Journal of Materials Chemistry A 2013 - vol. 1(Issue 34) pp:NaN4280-4280
Publication Date(Web):2013/06/25
DOI:10.1039/C3TB20296H
The fate of polymeric micelles (PMs) is mainly determined by their physicochemical properties, such as particle size, shape, and surface potential. Of these factors, the size effect of PMs plays a fundamental role. In this study, four different sizes of PMs with fluorescence-labeling were prepared to study the size-dependent biodistribution profiles as well as the anti-tumor efficacy in H22-subcutaneous hepatoma-bearing mice. Both ex vivo tumor imaging and in vivo real-time near-infrared (NIR) dye-tracking experiments indicated that sub-100 nm PMs have a higher extent of accumulation in tumor sites than >100 nm PMs. For normal tissues, smaller PMs (35 nm) tend to accumulate in the kidney and larger PMs (145 nm) tend to be captured by the spleen and lung, while middle-sized PMs (75 and 115 nm) tend to accumulate in the liver. Finally, doxorubicin (Dox) was used as the model drug to study the size-dependent anti-tumor efficacy of Dox-loaded micelles with H22-bearing mice and the results indicated that the smallest micellar drugs exhibited the best tumor-growth inhibition effect.
Co-reporter:Haiqin Song, Haihua Xiao, Yu Zhang, Haidong Cai, Rui Wang, Yonghui Zheng, Yubin Huang, Yuxin Li, Zhigang Xie, Tongjun Liu and Xiabin Jing
Journal of Materials Chemistry A 2013 - vol. 1(Issue 6) pp:NaN772-772
Publication Date(Web):2012/11/27
DOI:10.1039/C2TB00206J
A multifunctional hybrid platinum(IV) drug which has both DCA and Pt in one molecule was synthesized and tethered to polymers to further self-assemble into micelles. This micelle-mediated delivery of platinum(IV) prodrug aims to target both nuclear DNA and mitochondria.
Co-reporter:Ruogu Qi, Suhong Wu, Haihua Xiao, Lesan Yan, Wenliang Li, Xiuli Hu, Yubin Huang and Xiabin Jing
Journal of Materials Chemistry A 2012 - vol. 22(Issue 36) pp:NaN18922-18922
Publication Date(Web):2012/07/31
DOI:10.1039/C2JM33141A
The lack of safe and effective carriers for RNA interference therapeutics remains a barrier for its wide clinical application. In this study, guanidino groups were incorporated into poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(L-lysine) (mPEG-b-PCL-b-PLL, AG0) by simple replacement of the amino groups on PLL segments by the guanidino groups to enhance the transfection performance by mimicking the transmembrane function of cell penetrating peptides, such as TAT or other arginine-rich peptides. The guanidinated copolymers (AG1–AG3) displayed similar siRNA-binding capacity to AG0, but less cytotoxicity and higher silencing efficiency than AG0. Typically, AG3 with full replacement of the amino groups by guanidino groups exhibited higher silencing efficiency than PEI-25k and Lipofectamine 2000. Cell uptake and cell imaging experiments showed that the enhanced silencing efficiency of AG3–siRNA complex was due to the enhanced endocytosis cross the cell-membrane and the enhanced escape from the endosomes/lyosomes. The guanidino groups on the polylysine units were responsible for these enhancements although they are attached to the polymer backbone with a spacer of (CH2)4, in comparison with (CH2)3 in polyarginine. In conclusion, guanidination of mPEG-b-PCL-b-PLL resulted in a less toxic and more efficient siRNA vector and contribution of the guanidine groups to cell-membrane penetration and endosome/lyosome-membrane penetration was demonstrated. Therefore, replacement of the amino groups in conventional gene delivery vectors with guanidine groups might be a useful strategy of developing novel gene or drug delivery vectors.
Co-reporter:Xiuli Hu, Rui Wang, Jun Yue, Shi Liu, Zhigang Xie and Xiabin Jing
Journal of Materials Chemistry A 2012 - vol. 22(Issue 26) pp:
Publication Date(Web):
DOI:10.1039/C2JM31130E
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