Co-reporter:Jingjing Wu, Cui Tang, Chunhua Yin
Acta Biomaterialia 2017 Volume 47(Volume 47) pp:
Publication Date(Web):1 January 2017
DOI:10.1016/j.actbio.2016.10.012
In order to reduce toxicity and improve antitumor therapeutic effects of doxorubicin (DOX) and recombinant human interleukin-2 (rhIL-2), we developed a hydrophilic cationic polymer (N,N,N-trimethyl chitosan, TMC) based nanocomplexes (FTCD/rhIL-2) which could efficiently mediate systemic co-delivery of hydrophobic DOX and water-soluble rhIL-2 to achieve the purpose of combination therapy. DOX was covalently conjugated to TMC through cis-aconitic anhydride (CA) which endowed nanocomplexes a pH-sensitive release of DOX, while rhIL-2 was loaded through electrostatic adsorption without compromise of bioactivity. The resultant nanocomplexes exhibited sub-spherical shape (∼200 nm) and positive charge (>20 mV). Folate (FA) modification was utilized with the intention of active targeting, which was however correlated with weakened tumor growth inhibition, emphasizing the importance of balance in overcoming diverse delivery barriers for efficacious antitumor therapy. Compared with free drugs, FTCD/rhIL-2 nanocomplexes significantly delayed tumor growth, increased the serum immunoglobulin G (IgG) level and the amount of tumor infiltrated cytotoxic T lymphocytes. These results indicated that the combinational administration of DOX and rhIL-2 based on polymer nanoparticles could serve as an effective strategy in antitumor therapy.Statement of SignificanceCombined administration of doxorubicin (DOX) and recombinant human interleukin-2 (rhIL-2) has been utilized for the treatment of tumors. However the traditional administration brought to severe side effects, and the efficiency of current delivery systems were unsatisfactory. Herein we developed a hydrophilic cationic polymer based nanoparticle delivery system which facilitated simultaneous and systemic co-delivery of hydrophobic DOX and water-soluble rhIL-2. This system achieved pH-sensitive release of DOX and sustained release of rhIL-2 in vitro, meanwhile, improved anti-tumor efficacy and reduced side-effect in vivo. Thus, our study provided a solution for combinational administration of DOX and rhIL-2 and could serve as an effective strategy in antitumor therapy.Download high-res image (188KB)Download full-size image
Co-reporter:Rui He, Chunhua Yin
Acta Biomaterialia 2017 Volume 53(Volume 53) pp:
Publication Date(Web):15 April 2017
DOI:10.1016/j.actbio.2017.02.012
Paclitaxel (PTX) conjugated trimethyl chitosan (TMC-PTX) and folic acid (FA) modified TMC-PTX (FA-TMC-PTX) were developed as polymer-drug conjugates for oral and intravenous delivery of PTX. As amphiphilic conjugates, TMC-PTX and FA-TMC-PTX containing approximately 11 wt% PTX could self-assemble into spherical nanoparticles with average sizes of 170 and 187 nm, respectively. The conjugates presented a sustained release of PTX and the release rate was positively correlated with the pH value of medium ranging from 1.2 to 7.4. TMC-PTX and FA-TMC-PTX possessed enhanced mucoadhesion compared with trimethyl chitosan, and promoted ex vivo intestinal transport of PTX in comparison to PTX solution by 15.5 and 18.8 folds, respectively. Hemolysis assessment confirmed the safety of TMC-PTX and FA-TMC-PTX, and FA modification alleviated protein adsorption of the conjugates. Prolonged blood retention and increased PTX accumulation in the tumor were achieved for orally and intravenously administered conjugates. In H22 tumor-bearing mice, TMC-PTX delivered via oral or intravenous route showed superior tumor retardation and survival rate compared with intravenously injected PTX, and FA-TMC-PTX further enhanced the antitumor efficacy. Overall, the trimethyl chitosan based drug conjugates may have potential applications as a promising candidate for cancer therapy.Statement of SignificanceIn the current study, PTX conjugated trimethyl chitosan (TMC-PTX) and folic acid (FA) modified TMC-PTX (FA-TMC-PTX) were developed as the polymer-drug conjugates for oral and intravenous delivery of PTX. By exploiting advantages with respect to improved solubility of drugs, controlled release behavior of covalently linked drugs, and enhanced targeting effect towards tumors, improved tumor growth inhibition efficacy and prolonged survival time were achieved for TMC-PTX as compared with free PTX, and FA modification further enhanced the in vivo antitumor efficacy. Overall, the self-assembled nanoplatform of trimethyl chitosan based drug conjugates may have potential applications as a promising candidate for tumor therapy via different administration routes.Download high-res image (103KB)Download full-size image
Co-reporter:Lu Han, Cui Tang, and Chunhua Yin
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 36) pp:23498
Publication Date(Web):August 25, 2016
DOI:10.1021/acsami.6b07173
The application of cytotoxic chemotherapeutics in cancer therapy has been largely restricted by their lack of selectivity. Despite the existence of numerous targeted delivery systems, it is practically challenging to develop one single system to simultaneously cover tumor-targeted delivery of chemotherapeutics at the tissue, cellular, and subcellular levels. To solve this problem, pH-responsive core–shell structured nanoparticles (CSNPs) were self-assembled in this study to provide triple-stage targeted delivery of doxorubicin (DOX) from the injection site to the nuclei of cancer cells. Amino-functionalized mesoporous silica nanoparticles (MSN) were doubly modified with TAT peptide and acid-cleavable polyethylene glycol (PEG) as the DOX-loaded cationic core. The anionic shell was constituted by galactose-modified poly(allylamine hydrochloride)-citraconic anhydride, a hepato-carcinoma-targeting polymer with charge-reversible property. In vitro results showed that PEG effectively reduced protein adsorption and phagocytic capture of CSNPs in the circulating blood (pH 7.4), thus facilitating passive accumulation in tumors (tissue level). Following PEG detachment via acidic hydrolysis in tumor microenvironment (pH 6.5), the exposed galactose ligands endowed CSNPs with active internalization into hepato-carcinoma cells (cellular level). Afterward, the acidity in endosomes and lysosomes (pH 5.0) triggered the conversion of anionic shell into positive charges, leading to core–shell disassembly and subsequent TAT-mediated delivery of DOX to the nuclei (subcellular level). Importantly, the efficiencies of each targeting moiety were nicely preserved when combining together in CSNPs. As a result, improved tumorous distribution and potent therapeutic efficacy of CSNPs were noted in tumor-bearing mice at a relatively low dose. CSNPs therefore provide an efficient and nontoxic platform for the targeted delivery of antitumor drugs.Keywords: cancer therapy; core−shell structured nanoparticles; doxorubicin; pH sensitivity; targeted delivery
Co-reporter:Chunbai He, Lichen Yin, Yudong Song, Cui Tang, Chunhua Yin
Acta Biomaterialia 2015 Volume 17() pp:98-106
Publication Date(Web):15 April 2015
DOI:10.1016/j.actbio.2015.01.041
Abstract
Secretion of tumor necrosis factor-α (TNF-α) by macrophages plays a predominant role in the development and progression of various inflammatory diseases. In the current contribution, multifunctional nanoparticles (NPs) containing TNF-α siRNA targeting macrophages via oral administration were developed to knockdown TNF-α expression against acute hepatic injury in rats. Mannose-modified trimethyl chitosan-cysteine (MTC) NPs were prepared by self-assembly method (sa-MTC NPs), ionic gelation and siRNA entrapment method (en-MTC NPs), and ionic gelation and siRNA adsorption method (ad-MTC NPs). Among them, en-MTC NPs demonstrated the best stability against ionic challenges with desired siRNA integrity against nucleases. By targeting normal enterocytes and M cells that express mannose receptors, en-MTC NPs notably promoted intestinal absorption of siRNA in rats. They further facilitated siRNA internalization by rat peritoneal exudate cells (PECs) via lipid-raft involved endocytosis and macropinocytosis, thus inducing effective in vitro TNF-α knockdown. Orally delivered en-MTC NPs at a low siRNA dose of 50 μg/kg inhibited systemic TNF-α production and decreased TNF-α mRNA levels in macrophage-enriched liver, spleen, and lung tissues, which consequently protected rats from acute hepatic injury. Therefore, the en-MTC NPs would provide an effective approach to orally deliver TNF-α siRNA for the anti-inflammatory therapy.
Co-reporter:Lu Han, Cui Tang, Chunhua Yin
Biomaterials 2015 44() pp: 111-121
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.12.020
Co-reporter:Lu Han, Cui Tang, Chunhua Yin
Biomaterials 2015 60() pp: 42-52
Publication Date(Web):August 2015
DOI:10.1016/j.biomaterials.2015.05.001
Co-reporter:Bojie Yu, Cui Tang, Chunhua Yin
Biomaterials 2014 35(24) pp: 6369-6378
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.04.095
Co-reporter:Lu Han, Cui Tang, Chunhua Yin
Biomaterials 2014 35(15) pp: 4589-4600
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.02.027
Co-reporter:Lu Han, Cui Tang, Chunhua Yin
Biomaterials 2013 34(21) pp: 5317-5327
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.03.060
Co-reporter:Hao Zheng, Cui Tang, Chunhua Yin
Biomaterials 2013 34(13) pp: 3479-3488
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.01.072
Co-reporter:Jing Zhang, Cui Tang, Chunhua Yin
Biomaterials 2013 34(14) pp: 3667-3677
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.01.079
Co-reporter:Liming Cui, Cui Tang, Chunhua Yin
Carbohydrate Polymers 2012 Volume 87(Issue 4) pp:2505-2511
Publication Date(Web):1 March 2012
DOI:10.1016/j.carbpol.2011.11.030
Chitosan-N-trimethylaminoethylmethacrylate chloride (CS-TM) copolymers with different quaternization degrees (DQ, 30 and 50%) were synthesized and further modified with methoxypoly(ethylene glycol) (mPEG) of different molecular weights (MW, 2 and 5 kDa). The hydrophilicity of the resulting copolymers was significantly increased as evidenced by decreased contact angles. PEGylation with higher mPEG MW could significantly reduce the hemolytic potential, protein adsorption, cytotoxicity and intestinal mucosal damage of CS-TM (DQ of 50%, CS-TM50). PEGylation resulted in a considerable increase in the release of reducing sugars following 84-day lysozyme-catalyzed degradation, and an increase in mPEG MW led to a faster degradation of CS-TM50. The antioxidant activity of CS-TM50 was superior to that of PEGylated CS-TM50, exhibiting dose-dependent reducing power and lipid peroxidation inhibition effect. In conclusion, quaternization and subsequent PEGylation of CS with rational modification degree of its free amino group will be a potential strategy for the development of biocompatible and biodegradable CS derivatives.Highlights► The hydrophilicity of chitosan was increased after quaternization and PEGylation. ► mPEG with higher MW was more favorable for the improved biocompatibility. ► mPEG with higher MW facilitated lysozyme mediated degradation. ► Quaternized chitosan showed dose-dependent lipid peroxidation inhibition effect.
Co-reporter:Chunbai He, Lichen Yin, Cui Tang, Chunhua Yin
Biomaterials 2012 33(33) pp: 8569-8578
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.07.063
Co-reporter:Lili Shi, Cui Tang, Chunhua Yin
Biomaterials 2012 33(30) pp: 7594-7604
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.06.072
Co-reporter:Bingqing Wang, Chunbai He, Cui Tang, Chunhua Yin
Biomaterials 2011 32(20) pp: 4630-4638
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.03.003
Co-reporter:Xin Zhao, Lichen Yin, Jieying Ding, Cui Tang, Shaohua Gu, Chunhua Yin, Yumin Mao
Journal of Controlled Release 2010 Volume 144(Issue 1) pp:46-54
Publication Date(Web):21 May 2010
DOI:10.1016/j.jconrel.2010.01.022
Trimethyl chitosan–cysteine conjugate (TMC–Cys) was evaluated as non-viral gene carriers to combine the advantages of TMC and thiolated chitosan. TMC–Cys with various molecular weights (30, 100, and 200 kDa) and quaternization degrees (15 and 30%) was allowed to form polyelectrolyte nanocomplexes with plasmid encoding enhanced green fluorescence protein (pEGFP), which demonstrated preferable diameters of below 200 nm and zeta potentials of + 15 to + 20 mV. Cell binding and uptake of TMC–Cys/pEGFP nanocomplexes (TMC–Cys NC) were enhanced 2.4–3.0 and 1.4–3.0 folds, respectively, compared to TMC/pEGFP nanocomplexes (TMC NC). pEGFP could be easily released from TMC–Cys NC at the intracellular glutathione concentration, which promoted its nuclear transport and accumulation. Consequently, TMC–Cys NC showed a 1.4 to 3.2-fold increase in the transfection efficiency in HEK293 cells as compared to TMC NC and the optimal TMC–Cys(100,30) NC showed a 1.5-fold enhancement than Lipofectamine2000. Such results were further confirmed by in vivo transfection with a 2.3-fold and 4.1-fold higher transfection efficiency of TMC–Cys(100,30) NC than TMC(100,30) NC and Lipofectamine2000, respectively. Therefore, TMC–Cys/DNA nanocomplexes could be a promising gene delivery system with in vitro and in vivo superiority to Lipofectamine2000.Thiolated trimethyl chitosan (TMC–Cys)/pEGFP nanocomplexes improve both in vitro and in vivo transfection efficiency.
Co-reporter:Lichen Yin, Jieying Ding, Jing Zhang, Chunbai He, Cui Tang, Chunhua Yin
Biomaterials 2010 31(12) pp: 3347-3356
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.01.045
Co-reporter:Chunbai He, Yiping Hu, Lichen Yin, Cui Tang, Chunhua Yin
Biomaterials 2010 31(13) pp: 3657-3666
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.01.065
Co-reporter:Chunbai He, Fuying Cui, Lichen Yin, Feng Qian, Cui Tang, Chunhua Yin
European Polymer Journal 2009 Volume 45(Issue 2) pp:368-376
Publication Date(Web):February 2009
DOI:10.1016/j.eurpolymj.2008.11.004
A smart polymeric composite carrier consisting of carboxylated chitosan grafted nanoparticles (CCGN) and bilaminated films with one alginate-Ca2+ mucoadhesive layer and one hydrophobic backing layer was developed as a novel carrier for peptide. Calcein, hydrophilic and hydrolytic degradative, was entrapped into CCGN as a model peptide and its release behavior was investigated. Morphology study showed a uniform distribution of CCGN in the homogeneous and porous hydrogel. CCGN was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size measurement, and ζ potential measurement. The composite carrier was characterized by differential scanning calorimetry (DSC), scanning electron microscope (SEM) and fluorescence microscopy. The carrier exhibited high mucoadhesive force and pH-sensitivity, in that release of the nanoparticles and the model peptide calcein were both restricted in acidic environment while a fast and complete release was achieved in neutral medium. Therefore, this novel carrier would be a promising candidate for hydrophilic peptide drugs via oral administration.
Co-reporter:Fuying Cui;Chunbai He;Miao He;Cui Tang;Lichen Yin;Feng Qian
Journal of Biomedical Materials Research Part A 2009 Volume 89A( Issue 4) pp:1063-1071
Publication Date(Web):
DOI:10.1002/jbm.a.32071
Abstract
This manuscript describes the development of a new porous, flexible bilaminated film for buccal protein administration by a simple and mild casting procedure. It consists of a mucoadhesive layer (chitosan-ethylenediaminetetraacetic acid hydrogel film) containing protein drugs and an impermeable protective layer made of ethylcellose. The obtained mucoadhesive layer was characterized in terms of Fourier transform infrared spectroscopy, rheology, swelling, and mucoadhesion. Rheology results showed that chitosan-ethylenediaminetetraacetic acid hydrogel (10:2) possessed the greatest degree of viscoelasticity and was well-structured compared with other hydrogels. The in vitro mucoadhesion studies also showed that the mucoadhesive force of the hydrogel remained over 17,000 N/m2 during 4 h in the simulated oral cavity. The insulin loaded bilaminated film showed a pronounced hypoglycemic effect following buccal administration to healthy rats, achieving a 17% pharmacological availability compared with subcutaneous insulin injection. According to these results, the bilaminated film would be a promising delivery carrier for protein drugs via the buccal route. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Co-reporter:Fuying Cui, Feng Qian, Ziming Zhao, Lichen Yin, Cui Tang and Chunhua Yin
Biomacromolecules 2009 Volume 10(Issue 5) pp:
Publication Date(Web):March 17, 2009
DOI:10.1021/bm900035u
To improve the efficiency of insulin via oral administration, pH-sensitive carboxylated chitosan grafted poly(methyl methacrylate) nanoparticles (CCGN) were prepared. CCGN were characterized by 1H NMR, dynamic light scattering, zeta potential, and transmission electron microscopy, and the hypoglycemic effect of insulin loaded CCGN via the oral route was evaluated in normal and diabetic rats. CCGN exhibited a homogeneous morphology and a spherical shape with core−shell structure. They were aggregated in simulated gastric fluid while separated in simulated intestinal fluid. Insulin was mainly located in the shell of the CCGN via hydrogen bonding, electrostatic interaction, and Van der Waals force. Insulin release from the CCGN exhibited a pH-sensitive property in that it had a slow release rate at pH 2.0 and a fast release rate at pH 6.8 and 7.4. The pharmacological bioavailability after oral administration of insulin loaded CCGN at a dose of 25 IU/kg was found to be 9.7%. Besides, CCGN showed desirable tissue and blood compatibility. Therefore, the CCGN would be a promising delivery carrier for protein drugs via the oral route.
Co-reporter:Ziming Zhao, Miao He, Lichen Yin, Jiamin Bao, Lili Shi, Bingqing Wang, Cui Tang and Chunhua Yin
Biomacromolecules 2009 Volume 10(Issue 3) pp:
Publication Date(Web):January 28, 2009
DOI:10.1021/bm801225m
Novel chitosan derivatives carrying linoleic acid (LA) as hydrophobic moieties and poly(β-malic acid) (PMLA) as hydrophilic moieties (LA/PMLA double grafted chitosan, LMC) were synthesized. It self-assembled into nanoparticles of 190−350 nm in water, which carried negative surface charges in physiological pH. The critical aggregation concentration of the LMC deceased with an increase in the LA content. Paclitaxel (PTX) was loaded into the LMC nanoparticles with a high loading efficiency and the maximum loading capacity of 9.9 ± 0.4%. PTX−LMC nanoparticles exhibited a sustained release within 24 h in pH 7.4 phosphate-buffered saline (PBS), and the release rate was affected by the LA content and PMLA length. Hemolysis and acute toxicity assessment indicated that the LMC nanoparticles were safe drug carriers for i.v. administration. Additionally, PTX−LMC showed significantly potent tumor inhibition efficacy relative to that of TAXOL in S-180 bearing mice. Therefore, the LMC nanoparticles could be an effective and safe vehicle for systemic administration of hydrophobic drugs, especially PTX.
Co-reporter:Yu Zhang, Siyu Zhu, Lichen Yin, Feng Qian, Cui Tang, Chunhua Yin
European Polymer Journal 2008 Volume 44(Issue 6) pp:1654-1661
Publication Date(Web):June 2008
DOI:10.1016/j.eurpolymj.2008.03.019
A new type of nanocapsules with an oil core, coated by poly(ethylene glycol) (PEG) was designed. The loading efficiency and the biocompatibility of the polymeric nanocapsules were evaluated when it was used as a carrier for hydrophobic agent paclitaxel. The nanocapsules were synthesized through miniemulsion polymerization of butylcyanoacrylate (BCA) with PEG as initiator. The particle size and zeta potential of nanocapsules were influenced by the PEG content in the polymerization system. Fourier transform infrared (FTIR) spectra and 1H NMR demonstrated the chemical coupling between PEG and poly(butylcyanoacrylate) (PBCA). Thermal characteristics of the copolymer were investigated by differential scanning calorimetry (DSC). The encapsulation efficiency increased concurrently with the increase of the PEG content in the system. The hemolytic assay and the cytotoxicity measurement showed that the PEG coating could significantly reduce the hemolytic potential and cytotoxicity of the nanocapsules. The results showed that the PEG–PBCA nanocapsules could be an effective carrier for hydrophobic agents.
Co-reporter:Siyu Zhu, Feng Qian, Yu Zhang, Cui Tang, Chunhua Yin
European Polymer Journal 2007 Volume 43(Issue 6) pp:2244-2253
Publication Date(Web):June 2007
DOI:10.1016/j.eurpolymj.2007.03.042
Chitosan-N-trimethylaminoethylmethacrylate chloride–PEG (CS-TM–PEG) copolymers were synthesized in order to improve the solubility of chitosan in physiological environment, and enhance the biocompatibility of quaternized chitosan. The result of 1H NMR confirmed that PEG had been combined with amino groups of quaternized chitosan. The profile of hemolysis assay showed that Chitosan-N-trimethylaminoethylmethacrylate chloride (CS-TM) copolymer exhibited hemolytic activity from 10.31% to 13.58%, while CS-TM–PEG copolymer had hemolytic activity from 4.76% to 7.05% at copolymer concentrations from 250 to 2000 μg/ml. Through PEG modification, the hemolytic activity could be reduced to a half. CS-TM–PEG copolymer–insulin nanoparticles were prepared based on ionic gelation process of positively charged copolymers and negatively charged insulin. The nanoparticles were characterized in terms of particle size, TEM, association efficiency and in vitro release. These nanoparticles were 200–400 nm in size and insulin association efficiency of optimal formulations was found up to 90%. In vitro release showed that the nanoparticles provided an initial burst release followed by a sustained release with the sensitivity of ionic strength and pH values.
Co-reporter:Huaizhi Dou;Min Zhang;Yu Zhang
Chemical Biology & Drug Design 2007 Volume 69(Issue 2) pp:
Publication Date(Web):21 MAR 2007
DOI:10.1111/j.1747-0285.2007.00479.x
Monomethoxypoly(ethylene glycol) 5000 (mPEG5K) and 2000 (mPEG2K) were activated to produce mPEG-aldehyde with content over 80%. Effects of reaction time, pH and initial molar ratio of mPEG-aldehyde to insulin on synthesis of PEGylated insulin were studied, taking mPEG5K-aldehyde as a model. On the optimized condition, approximately 90% of product was mono-PEGylated insulin. Mono-PEGylated insulin was purified by ion-exchange chromatography. The purity of each component was analysed by RP-HPLC and the results showed an efficient purification. Matrix assistant laser desorption ionization time-of-flight mass spectra demonstrated that the modification site of mono-PEGylated insulin was PheB1. The biological activity of all PEGylated insulin was also evaluated.
Co-reporter:Lichen Yin;Likun Fei;Cui Tang
Polymer International 2007 Volume 56(Issue 12) pp:
Publication Date(Web):29 MAY 2007
DOI:10.1002/pi.2306
In this investigation an interpenetrating polymer network–superporous hydrogel containing sodium alginate (IPN-SPHAlg) was synthesized. The morphology of the polymer was characterized using scanning electron microscopy, light images and porosity, and the polymer was further examined by swelling ratio, mechanical strength and biocompatibility. The results indicated that the IPN-SPHAlg possessed both large numbers of interconnected pores and an interpenetrating network. The swelling ratio of IPN-SPHAlg was lower than that of the superporous hydrogel (SPH) and it decreased as the sodium alginate/monomer ratio increased. The IPN-SPHAlg exhibited pH responsiveness and salt-sensitive properties. Compared to SPH and SPH composites, the mechanical strength of IPN-SPHAlg was significantly enhanced. Thiazolyl blue assay on AD293 cells, in situ lactate dehydrogenase assay and morphological study of rat intestine showed that the polymer induced no significant cell or mucosal damage. The fast swelling, good mechanical properties, pH sensitivity and biocompatibility of the IPN-SPHAlg suggested it as a potential candidate in the field of drug-delivery systems. Copyright © 2007 Society of Chemical Industry
Co-reporter:Cui Tang;Lichen Yin;Jing Yu;Yuanying Pei
Journal of Applied Polymer Science 2007 Volume 104(Issue 5) pp:2785-2791
Publication Date(Web):27 FEB 2007
DOI:10.1002/app.25930
Carbopol-containing superporous hydrogel composites (SPHCc) with fast swelling and high swelling ratio were prepared using free radical copolymerization. Swelling behavior of the SPHCc was studied in various salt and pH solutions and their biocompatibility was evaluated using tissue damage and cytotoxicity studies. The swelling ratio of the SPHCc decreased with the increase of Carbopol/monomer ratio and was sensitive to pH and ionic strength of the swelling medium. The release of insulin from the SPHCc was rapid in 0.01M phosphate buffered saline (PBS, pH 7.4). In the jejunum mucosal membrane toxicity studies in rat, no significant morphological damage was observed after application of SPHCc. Besides, no damage of the Caco-2 monolayers was detected after incubation with SPHCc in the trypan blue and propidium iodide tests. On the basis of these results, it was concluded that the SPHCc might be a safe and effective carrier for peroral delivery of peptide and protein drugs. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Co-reporter:Feng Qian, Fuying Cui, Chunhua Yin
European Polymer Journal 2006 Volume 42(Issue 7) pp:1653-1661
Publication Date(Web):July 2006
DOI:10.1016/j.eurpolymj.2006.01.016
Methylmethacrylate copolymer nanoparticles with different hydrophilic chains were prepared by the free radical polymerization of methylmethacrylate with N-isopropylacrylamide (NIPAAm), N-methacrylic acid (MAA), N-trimethylaminoethylmethacrylate chloride (TMAEMC) or N-dimethylaminoethylmethacrylate hydrochloride (DMAEMC). These particles were characterized by particle size and zeta potential. The polymerization conditions were shown to influence the particle size and surface charge. Particle sizes of MMA–NIPAAm nanoparticles after 3 h of reaction reached constant level at 180 nm. An increasing amount of total monomer (0.5–5%) would result in the nanoparticles of particle size of 115–204 nm for 30% NIPAAm of the total monomer. In the same range of 5–40% NIPAAm of the total monomer, the particle size decreased from 280 to 170 nm. The concentration of the initiator APS up to a concentration of 0.2% for MMA–TMAEMC and 0.1% for MMA–NIPAAm showed no effect on the particle size of the final nanoparticle suspensions, while higher concentration would lead to aggregation in the polymerization process. MMA–NIPAAm nanoparticles were pH-dependent in zeta potential at pH 1–12 values reducing from 12.2 mV to −16.8 mV, respectively. Nanoparticles were incubated with pepsin and trypsin at 37 °C for 20 min and their enzyme inhibition was determined. The activity of pepsin decreased to 27% in the presence of MMA–NIPAAm nanoparticles, and MMA–MAA nanoparticles reduced the activity of trypsin to 39%, respectively.
Co-reporter:Cui Tang, Chunhua Yin, Yuanying Pei, Min Zhang, Lifang Wu
European Polymer Journal 2005 Volume 41(Issue 3) pp:557-562
Publication Date(Web):March 2005
DOI:10.1016/j.eurpolymj.2004.10.017
In this investigation new superporous hydrogels composites based on aqueous Carbopol® solution (SPHCcs) were prepared. SEM images indicated that the inner surface of SPHCcs contained a lot of pores connected each other and the outer surface of them was non-porous. The swelling ratio decreased with increasing the content of aqueous Carbopol® solution, and the final swelling ratio was similar to that of the SPH although the initial swelling ratio was lower. The density measurement revealed that the porosity increased when aqueous Carbopol® solution was incorporated. It was observed from in vitro bioadhesive force study that SPHCcs adhered to the intestinal mucosal more quickly and exhibited higher mucoadhesion as compared with SPH. It is evident that the hydrogels synthesized in this study could be a potential candidate for transmucosal drug delivery system.
Co-reporter:Chunhua Yin, Cui Tang, Xiaoying Wu
Journal of Pharmaceutical and Biomedical Analysis 2003 Volume 33(Issue 1) pp:39-43
Publication Date(Web):15 September 2003
DOI:10.1016/S0731-7085(03)00352-2
A high-performance liquid chromatography procedure for the simultaneous determination of aminophylline, methoxyphenamine hydrochloride, noscapine and chlorphenamine maleate in commercially available compound capsule dosage forms has been developed and validated. The separation and quantification were achieved on an Ultrasphere™ C18 column using a mobile phase of dichloromethane–methanol–0.25% (v/v) diethylamine aqueous solution (20:60:20, v/v/v) at a flow rate of 1 ml min−1 with detection of all analytes at 264 nm. The separation was achieved within 6 min for each drug mixture. The method showed good linearity for the aminophylline, noscapine, chlorphenamine maleate and methoxyphenamine hydrochloride mixture in the 125–750, 35–210, 10–60 and 62.5–375 μg ml−1 ranges, respectively. The intra- and inter-day R.S.D.s ranged from 0.4 to 0.5%, 0.4–0.6%, 0.5–0.7% and 0.4–0.6% for aminophylline, noscapine, chlorphenamine maleate and methoxyphenamine hydrochloride, respectively. The recoveries (mean±S.D.) of low, middle and high concentrations were 99.9±0.9, 100.4±1.3 and 99.7±0.7% for aminophylline; 99.9±1.1, 100.4±0.7 and 100.1±0.8% for noscapine; 99.8±1.1, 99.7±1.0 and 100.7±0.8% for chlorphenamine maleate; and 99.8±0.9, 100.4±1.6 and 99.9±0.9% for methoxyphenamine hydrochloride, respectively.
