Co-reporter:Yuanwen Wang;Shicheng Wang;Caleb Kesse Firempong;Huiyun Zhang
AAPS PharmSciTech 2017 Volume 18( Issue 3) pp:586-594
Publication Date(Web):2017 April
DOI:10.1208/s12249-016-0537-8
This study was aimed at preparing orally administered naringenin-loaded liposome for pharmacokinetic and tissue distribution studies in animal models. The liposomal system, consisting of phospholipid, cholesterol, sodium cholate, and isopropyl myristate, was prepared using the thin-film hydration method. Physicochemical characterization of naringenin-loaded liposome such as particle size, zeta potential, and encapsulation efficiency produced 70.53 ± 1.71 nm, −37.4 ± 7.3 mV, and 72.2 ± 0.8%, respectively. The in vitro release profile of naringenin from the formulation in three different media (HCl solution, pH 1.2; acetate buffer solution, pH 4.5; phosphate buffer solution, pH 6.8) was significantly higher than the free drug. The in vivo studies also revealed an increase in AUC of the naringenin-loaded liposome from 16648.48 to 223754.0 ng·mL−1 h as compared with the free naringenin. Thus, approximately 13.44-fold increase in relative bioavailability was observed in mice after oral administration. The tissue distribution further showed that the formulation was very predominant in the liver. These findings therefore indicated that the liposomal formulation significantly improved the solubility and oral bioavailability of naringenin, thus leading to wider clinical applications.
Co-reporter:Jie Zhou, Wenwen Deng, Yan Wang, Xia Cao, Jingjing Chen, Qiang Wang, Wenqian Xu, Pan Du, Qingtong Yu, Jiaxin Chen, Myron Spector, Jiangnan Yu, Ximing Xu
Acta Biomaterialia 2016 Volume 42() pp:209-219
Publication Date(Web):15 September 2016
DOI:10.1016/j.actbio.2016.06.021
Abstract
Carbon quantum dots (CQDs), unlike semiconductor quantum dots, possess fine biocompatibility, excellent upconversion properties, high photostability and low toxicity. Here, we report multifunctional CQDs which were developed using alginate, 3% hydrogen peroxide and double distilled water through a facile, eco-friendly and inexpensive one-step hydrothermal carbonization route. In this reaction, the alginate served as both the carbon source and the cationization agent. The resulting CQDs exhibited strong and stable fluorescence with water-dispersible and positively-charged properties which could serve as an excellent DNA condensation. As non-viral gene vector being used for the first time, the CQDs showed considerably high transfection efficiency (comparable to Lipofectamine2000 and significantly higher than PEI, p < 0.05) and negligible toxicity. The photoluminescence properties of CQDs also permitted easy tracking of the cellular-uptake. The findings showed that both caveolae- and clathrin-mediated endocytosis pathways were involved in the internalization process of CQDs/pDNA complexes. Taken together, the alginate-derived photoluminescent CQDs hold great potential in biomedical applications due to their dual role as efficient non-viral gene vectors and bioimaging probes.
Statement of Significance
This manuscript describes a facile and simple one-step hydrothermal carbonization route for preparing optically tunable photoluminescent carbon quantum dots (CQDs) from a novel raw material, alginate. These CQDs enjoy low cytotoxicity, positive zeta potential, excellent ability to condense macromolecular DNA, and most importantly, notably high transfection efficiency. The interesting finding is that the negatively-charged alginate can convert into positively charged CQDs without adding any cationic reagents. The significance of this study is that the cationic carbon quantum dots play dual roles as both non-viral gene vectors and bioimaging probes at the same time, which are most desirable in many fields of applications such as gene therapy, drug delivery, and bioimaging.
Co-reporter:Yang Xu, Qilong Wang, Yingshu Feng, Caleb Kesse Firempong, Yuan Zhu, Emmanuel Omari-Siaw, Yuanyuan Zheng, Zunqin Pu, Ximing Xu, Jiangnan Yu
Journal of Functional Foods 2016 Volume 27() pp:703-710
Publication Date(Web):December 2016
DOI:10.1016/j.jff.2016.10.007
•An effective method for isolating [6]-Gingerol from ginger was established.•An optimal formulation of [6]-Gingerol-loaded-SMEDDS was successfully developed.•In vitro release profile of [6]-Gingerol from SMEDDS was significantly enhanced.•The SMEDDS effectively improved the oral bioavailability of [6]-Gingerol.The purpose of this study was to develop a [6]-Gingerol-loaded self-microemulsifying drug delivery system ([6]-Gingerol-SMEDDS) for oral administration and enhanced bioavailability of the drug. The [6]-Gingerol-SMEDDS, consisting of oils (ethyl oleate), surfactant (Cremophor EL35) and co-surfactant (1,2-propanediol), showed an acceptable spherical nanoparticle with stable physicochemical properties such as the mean droplet size (73.06 ± 0.49 nm), zeta potential (−2.45 ± 0.41) and encapsulation efficiency (89.40 ± 1.11%). The in vitro release of [6]-Gingerol from the delivery system in the three different media (HCl, pH 1.2; Double distilled water, pH 7.0; phosphate buffer solution, pH 7.4) was significantly higher than in the free drug. The [6]-Gingerol-SMEDDS also exhibited prolonged plasma circulation which led to 6.58-fold increase in oral bioavailability compared with the free drug. These findings indicated that the developed [6]-Gingerol-SMEDDS could be a promising alternative in improving the solubility and oral bioavailability of [6]-Gingerol, as well as increasing its biological applications.
Co-reporter:Wenwen Deng, Xia Cao, Yan Wang, Qingtong Yu, Zhijian Zhang, Rui Qu, Jingjing Chen, Genbao Shao, Xiangdong Gao, Ximing Xu, and Jiangnan Yu
Journal of Agricultural and Food Chemistry 2016 Volume 64(Issue 6) pp:1264-1273
Publication Date(Web):January 26, 2016
DOI:10.1021/acs.jafc.5b05661
Pleurotus eryngii is a medicinal/edible mushroom with great nutritional value and bioactivity. Its polysaccharide has recently been developed into an effective gene vector via cationic modification. In the present study, cationized P. eryngii polysaccharide (CPS), hybridized with calcium phosphate (CP), was used to codeliver plasmids (Oct4, Sox2, Klf4, c-Myc) for generating induced pluripotent stem cells (iPSCs). The results revealed that the hybrid nanoparticles could significantly enhance the process and efficiency of reprogramming (1.6-fold increase) compared with the CP nanoparticles. The hybrid CPS also facilitated epigenetic modification during the reprogramming. Moreover, these hybrid nanoparticles exhibited multiple pathways (both caveolae- and clathrin-mediated endocytosis) in their cellular internalization, which accounted for the improved iPSCs generation. These findings therefore present a novel application of P. eryngii polysaccharide in pluripotent reprogramming via active epigenetic modification.
Co-reporter:Wenwen Deng, Xia Cao, Jingjing Chen, Zhijian Zhang, Qingtong Yu, Yan Wang, Genbao Shao, Jie Zhou, Xiangdong Gao, Jiangnan Yu, and Ximing Xu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 34) pp:18957
Publication Date(Web):August 13, 2015
DOI:10.1021/acsami.5b06768
Induced pluripotent stem cells (iPSCs), resulting from the forced expression of cocktails out of transcription factors, such as Oct4, Sox2, Klf4, and c-Myc (OSKM), has shown tremendous potential in regenerative medicine. Although rapid progress has been made recently in the generation of iPSCs, the safety and efficiency remain key issues for further application. In this work, microRNA 302-367 was employed to substitute the oncogenic Klf4 and c-Myc in the OSKM combination as a safer strategy for successful iPSCs generation. The negatively charged plasmid mixture (encoding Oct4, Sox2, miR302-367) and the positively charged cationized Pleurotus eryngii polysaccharide (CPEPS) self-assembled into nanosized particles, named as CPEPS-OS-miR nanoparticles, which were applied to human umbilical cord mesenchymal stem cells for iPSCs generation after characterization of the physicochemical properties. The CPEPS-OS-miR nanoparticles possessed spherical shape, ultrasmall particle size, and positive surface charge. Importantly, the combination of plasmids Oct4, Sox2, and miR302-367 could not only minimize genetic modification but also show a more than 50 times higher reprogramming efficiency (0.044%) than any other single or possible double combinations of these factors (Oct4, Sox2, miR302-367). Altogether, the current study offers a simple, safe, and effective self-assembly approach for generating clinically applicable iPSCs.Keywords: induced pluripotent stem cells; microRNAs; nanoparticles; polysaccharides; self-assembly;
Co-reporter:Caleb Kesse Firempong, Xia Cao, Shanshan Tong, Jiangnan Yu and Ximing Xu
RSC Advances 2015 vol. 5(Issue 61) pp:49330-49342
Publication Date(Web):28 May 2015
DOI:10.1039/C5RA08322B
A recently discovered receptor-rich lipid raft, which is linked to numerous transmembrane signal transduction pathways, has emerged as a medically significant biomaterial for screening antitumor agents. Compounds that interact with the biomaterial might potentially inhibit cancer cell growth, and thus be valuable as antitumor agents. Two standard anticancer drugs, lestaurtinib and gefitinib, interacted with the tropomyosin-related tyrosine kinase A (TrkA) receptor-rich lipid raft. The fact that they are both well known inhibitors of TrkA receptor strengthened the observed linkage. There is now a considerable interest in developing other related biomaterials to serve a similar purpose, and more importantly, support the concept of multitarget drug discovery. It is expected that new anticancer drugs strategically act on multiple pathways to achieve optimal therapeutic efficacies and decreased stimulation of acquired resistance. However, the current conventional approaches such as chemical screening systems and in silico methods cannot fully satisfy the increasing demand for the therapeutic agents. It has therefore become imperative to explore other alternatives to increase the number of clinically important antitumor agents. Here, we report the prospect of establishing lipid raft biomaterial with well endowed multiple cancer-related receptors for screening antitumor leads that affect multiple pathways. This review also examines receptor–ligand interactions in the hunt for novel antitumor agents and the associated key receptors.
Co-reporter:Yuan Zhu, Wei Peng, Jiajia Zhang, Miaomiao Wang, Caleb Kesse Firempong, Chunlai Feng, Hongfei Liu, Ximing Xu, Jiangnan Yu
Journal of Functional Foods 2014 Volume 8() pp:358-366
Publication Date(Web):May 2014
DOI:10.1016/j.jff.2014.04.001
•Capsaicin-loaded PVP/sodium cholate/lecithin mixed micelles were firstly prepared.•The capsaicin-loaded micelles were characterized in vitro.•The oral bioavailability of encapsulated capsaicin was investigated in rats.•A reduced irritation of capsaicin-loaded micelles on the gastric mucosa was observed.The aim of this study was to prepare capsaicin-loaded micelle for oral administration and pharmacokinetic studies in rats. The formulated capsaicin consisted of polyvinylpyrrolidone (PVP)/sodium cholate/phospholipid mixed micellar system. Spherical and physicochemical stable micelles were obtained with a particle size below 50 nm and zeta potential of less than −30 mV. The in vitro release of capsaicin from the micellar system in three different media (pH 7.4 phosphate buffer solution, pH 1.2 HCl solution and double distilled water) was significantly higher than that of free capsaicin. After oral administration, the formulated capsaicin exhibited a prolonged plasma circulation with the oral bioavailability increasing to 2.42-fold as compared with the free capsaicin. Additionally, a reduced irritation of capsaicin-loaded micelle on the gastric mucosa was observed. This novel micellar formulation significantly improved the oral bioavailability of capsaicin and brought a series of notable advantages for its oral delivery.
Co-reporter:Shanshan Tong;Min Fu;Xia Cao;Caleb Kesse Firempong;Chengxue Yi
Chromatographia 2014 Volume 77( Issue 5-6) pp:419-429
Publication Date(Web):2014 March
DOI:10.1007/s10337-014-2623-y
For the first time, a novel biological affinity separating system called lipid raft stationary phase chromatography (LRSC) was developed. It was employed to screen bioactive components from Chinese gallnut, a traditional Chinese medicine (TCM). The LRSC was prepared by the addition of activated silica to Tris–HCl solution, which contains the isolated lipid rafts of U251 cells. This was followed by agitation, washing, centrifugation and then re-suspension of the residue in another Tris–HCl solution. The lipid rafts possess abundant receptor tyrosine kinase, specifically tropomyosin-related kinase A (TrkA), which is a widely researched anti-tumor drug target. Thus, TrkA provided the LRSC model with the ability to select fractions that specifically interact with it. Using a non-TrkA targeted anti-tumor drug (gemcitabine) and TrkA targeted anti-tumor drugs (lestaurtinib and gefitinib) as controls to evaluate the specific affinity of the LRSC column, the different fractions of Chinese gallnut were subjected to LRSC screening for the identification of anti-tumor components. As a result, the ether fraction of Chinese gallnut manifested desirable affinity properties. The methyl thiazolyl tetrazolium assay confirmed the anti-tumor effect of the screened ether fraction, and more importantly, the ether fraction failed woefully to exhibit its anti-proliferative activity in the presence of TrkA inhibitors (K252a and primary antibody). This further proves the selectivity of LRSC on TrkA-targeted drugs. The LRSC model has, therefore, shown to be of high efficiency and selectivity in screening bioactive components from the complex TCM extracts, thus offering an effective approach for the development of anticancer natural products.
Co-reporter:Xia Cao;Wenwen Deng;Rui Qu;Qingtong Yu;Jun Li;Yan Yang;Yue Cao;Xiangdong Gao;Ximing Xu
Advanced Functional Materials 2013 Volume 23( Issue 43) pp:5403-5411
Publication Date(Web):
DOI:10.1002/adfm.201203646
Abstract
Generating of induced pluripotent stem cells (iPSCs) can be achieved by ectopic expression of defined transcription factor sets. However, most instances of iPSC induction have been achieved using viral vectors, which carry the risk of unpredictable genetic dysfunction. Here, for the first time, a non-viral vector based on calcium phosphate nanoparticles for the generation of virus-free iPSCs from human umbilical cord mesenchymal stem cells (HUMSCs) via co-delivery of the four plasmids (Oct4, Sox2, Klf4, and c-Myc) is reported. As a result, a total of 98 colonies from 200 000 cells have been obtained, with a reprogramming efficiency of 0.049%. The iPSCs shows positive expression of pluripotency markers, including OCT4, SSEA-3, SSEA-4, NANOG, and TRA-1-81. Moreover, the iPSCs are able to differentiate into all three germ layers in vitro. Subcutaneous injection of the iPSCs into immunocompromised mice results in the formation of teratomas containing a variety of tissues from all three germ layers. These findings indicate that co-delivery of the four Yamanaka factors via plasmid-encapsulated calcium phosphate nanoparticles can provide a simple, safe, and efficient method for the generation of virus-free iPSCs, which is crucial for their future clinical applications in the field of regenerative medicine.
Co-reporter:Chengxue Yi, Min Fu, Xia Cao, Shanshan Tong, Qianfeng Zheng, Caleb Kesse Firempong, Xinyi Jiang, Ximing Xu, and Jiangnan Yu
Journal of Agricultural and Food Chemistry 2013 Volume 61(Issue 25) pp:5961-5971
Publication Date(Web):May 30, 2013
DOI:10.1021/jf3055278
This study innovatively investigated the anticancer effect of Flammulina velutipes sterols (FVSs), the in vivo pharmacokinetics, and the tissue distribution of FVS-loaded liposomes. The FVS consisting of mainly 54.8% ergosterol and 27.9% 22,23-dihydroergosterol exhibited evident in vitro antiproliferative activity (liver HepG-2, IC50 = 9.3 μg mL–1; lung A549, IC50 = 20.4 μg mL–1). To improve the poor solubility of FVS, F. velutipes sterol liposome (FVSL) was originally prepared. The encapsulation efficiency of ergosterol was 71.3 ± 0.1% in FVSL, and the encapsulation efficiency of 22,23-dihydroergosterol was 69.0 ± 0.02% in FVSL. In comparison to its two free sterol counterparts, the relative bioavailability of ergosterol and 22,23-dihydroergosterol in FVSL was 162.9 and 244.2%, respectively. After oral administration in Kunming mice, the results of tissue distribution demonstrated that the liposomal FVS was distributed mostly in liver and spleen. The drug was eliminated rapidly within 4 h. These findings support the fact that FVS, a potential nutraceutical and an effective drug for the treatment of liver cancer, could be encapsulated in liposomes for improved solubility and bioavailability.
Co-reporter:Wenwen Deng, Min Fu, Yue Cao, Xia Cao, Miao Wang, Yan Yang, Rui Qu, Jun Li, Ximing Xu, Jiangnan Yu
Nanomedicine: Nanotechnology, Biology and Medicine 2013 Volume 9(Issue 8) pp:1181-1191
Publication Date(Web):November 2013
DOI:10.1016/j.nano.2013.05.008
This study centers on the use of a nanoparticle based on the polysaccharide from Angelica sinensis (ASP) as an efficient and safe non-viral gene vector. After modification with branched low molecular weight polyethylenimine (1200 Da), the cationized ASP (cASP) was combined with the plasmid encoding transforming growth factor-beta 1 (TGF-β1) to form a spherical nano-scaled particle (i.e., cASP-pTGF-β1 nanoparticle). This nanoparticle was applied to transfect rat bone marrow mesenchymal stem cells and human umbilical cord mesenchymal stem cells. As a result, nanoparticles (cASP/pDNA weight ratio 10:1) had the greatest transfection efficiency in both cells, which was significantly higher than those of Lipofectamine2000 and PEI (25 kDa). This was in agreement with the findings of the semi-quantitative RT-PCR and live cell imaging. These nanoparticles were also less toxic than Lipofectamine2000 and PEI (25 kDa). Therefore, cASP could be a potential candidate for a novel non-viral gene vector.From the Clinical EditorThese authors demonstrate the use of a nanoparticle-based efficient and safe non-viral gene vector delivery system via a spherical nanoparticle based on a polysaccharide from Angelica sinensis, with parameters superior to Lipofectamine2000.A polysaccharide extracted from the traditional Chinese herb Angelica sinensis (ASP) was chemically modified by the positively-charged low molecular weight polyethylenimine (LMW PEI) (1200 Da) to obtain the cationized ASP (cASP). The resulting cASP had the ability to condense and encapsulate plasmid TGF-β1 (pTGF-β1) to form nanoscaled particles (i.e., cASP-pTGF-β1 nanoparticles). These nanoparticles exhibited high transfection efficiency and low toxicity in both BMMSCs and HUMSCs.
Co-reporter:Xia Cao, Min Fu, Liang Wang, Hongfei Liu, Wenwen Deng, Rui Qu, Weiyan Su, Yawei Wei, Ximing Xu, Jiangnan Yu
Acta Biomaterialia 2012 Volume 8(Issue 6) pp:2104-2112
Publication Date(Web):July 2012
DOI:10.1016/j.actbio.2012.02.011
Abstract
The purpose of this study was to develop porous silica nanoparticles (PSNs) as a carrier to improve oral bioavailability of poorly water-soluble drugs, using silymarin as a model. PSNs were synthesized by reverse microemulsion and ultrasonic corrosion methods. A 3-day release formulation consisting of a silymarin solid dispersion, a hydrophilic gel matrix and silymarin-loaded PSNs was prepared. In vitro release studies indicated that both the silymarin-loaded PSNs and the 3-day release formulation showed a typical sustained-release pattern over a long period, about 72 h. The in vivo studies revealed that the 3-day release formulation gave a significantly higher plasma concentration and larger area under the concentration–time curves than commercial tablets when orally administered to beagle dogs. This implies that the prepared 3-day release formulation significantly enhanced the oral bioavailability of silymarin, suggesting that PSNs can be used as promising drug carriers for oral sustained release systems. Thus providing a technically feasible approach for improving the oral bioavailability and long-term efficacy of poorly soluble drugs.
Co-reporter:Miao Wang, Wenwen Deng, Min Fu, Xia Cao, Yan Yang, Weiyan Su, Jiangnan Yu, Ximing Xu
Carbohydrate Polymers 2011 86(4) pp: 1509-1518
Publication Date(Web):
DOI:10.1016/j.carbpol.2011.06.073
Co-reporter:Zengquan Gu, Xiaolei Shi, Emmanuel Omari-Siaw, Yuan Zhu, ... Ximing Xu
Journal of Drug Delivery Science and Technology (February 2017) Volume 37() pp:184-193
Publication Date(Web):1 February 2017
DOI:10.1016/j.jddst.2017.01.002
Ginkgo biloba extract (GBE50), the fifth generation extract of Ginkgo biloba, has been widely used in clinical treatment. This study was aimed at developing self-microemulsifying drug delivery system sustained-release pellets (SMEDDS-SR pellets) to achieve sustained release and increased the oral bioavailability of GBE50. Solubility studies and Pseudo-ternary phase diagrams were investigated to optimize the suitable compositions of SMEDDS-SR pellets. The optimal formulation of GBE50-SMEDDS consisting of oil (16.7% MCT), surfactant (33.4% Cremophor EL35), cosurfactant (33.4% PEG 400) and drug (16.7% GBE50) was obtained. The GBE50-SMEDDS-SR pellets were prepared by mixing GBE50-SMEDDS with diluent agent (MCC), disintegration agent (PVPP) and coating material of ethyl cellulose (EC) using extrusion spheronization method. The Morphology study of GBE50-SMEDDS-SR pellets after dispersion in water revealed a spherical and homogeneous structure of droplets (51.6 ± 1.8) nm. The in vitro release data revealed the sustained-release effect of GBE50-SMEDDS-SR pellets. Pharmacokinetics study in beagle dogs after oral administration yielded relative bioavailability (Fr) of 160.24% and 236.18% for GBE50-SMEDDS and GBE50-SMEDDS-SR pellets, respectively. Collectively, these results indicated that the SMEDDS-SR pellets could be an effective delivery system to achieve sustained release and improved oral bioavailability of GBE50.Download high-res image (251KB)Download full-size image
Co-reporter:Caleb Kesse Firempong, Hui-Yun Zhang, Jia-Jia Zhang, Yan Wang, Xia Cao, Emmmanuel Omari-Siaw, Shan-Shan Tong, Jiangnan Yu, Ximing Xu
European Journal of Integrative Medicine (August 2015) Volume 7(Issue 4) pp:365-371
Publication Date(Web):1 August 2015
DOI:10.1016/j.eujim.2015.07.026
IntroductionThe quest for novel cancer drugs is one of the most significant studies in natural products, and Chinese herbs with its promising antitumor properties cannot be exempted from this chemotherapeutic bracket. This study was therefore aimed at piloting the use of receptor-rich lipid raft biomaterial as a mass screening tool for rapid isolation of effective antitumor components from some Chinese herbs used in the treatment of diseases consistent with cancer symptoms.MethodAqueous crude extracts from 10 different Chinese herbs (Paeonia suffruticosa, Vaccaria segetalis, Terminalia chebula, Trichosanthes kirilowii, Arisaema erubescens, Morus australis, Centella asiatica, Rhematoxylon campechianum, Trachelospermum jasminoides and Taraxacum officinale) were screened using lipid raft silica beads. The identified bioactive products were separated into various fractions (petroleum ether, ethyl acetate, n-butanol and raffinate extracts) with another affinity screening analysis. Conventional MTT bioassay was employed to authenticate the susceptibility of liver cancer cells to the final bioactive isolates.ResultsThe results showed that only Vaccaria segetalis and Arisaema erubescens significantly interacted with the system. The MTT bioassay further confirmed the cytotoxicity of these plants and the data correlated very well with its reported cancer-related activities.ConclusionThese findings support the reliable application of the lipid raft biomaterial as a prospective mass screening technique for antitumor natural products.Download high-res image (157KB)Download full-size image
Co-reporter:Yingshu Feng, Congyong Sun, Yangyang Yuan, Yuan Zhu, Jinyi Wan, Caleb Kesse Firempong, Emmanuel Omari-Siaw, Yang Xu, Zunqin Pu, Jiangnan Yu, Ximing Xu
International Journal of Pharmaceutics (30 March 2016) Volume 501(Issues 1–2) pp:342-349
Publication Date(Web):30 March 2016
DOI:10.1016/j.ijpharm.2016.01.081
In the present study, a formulation system consisting of cholesterol and phosphatidyl choline was used to prepare an effective chlorogenic acid-loaded liposome (CAL) with an improved oral bioavailability and an increased antioxidant activity. The developed liposomal formulation produced regular, spherical and multilamellar-shaped distribution nanoparticles. The pharmacokinetic analysis of CAL compared with chlorogenic acid (CA), showed a higher value of Cmax(6.42 ± 1.49 min versus 3.97 ± 0.39 min) and a delayed Tmax(15 min versus 10 min), with 1.29-fold increase in relative oral bioavailability. The tissue distribution in mice also demonstrated that CAL predominantly accumulated in the liver which indicated hepatic targeting potential of the drug. The increased activities of antioxidant enzymes (Total Superoxide Dismutase (T-SOD) and Glutathione Peroxidase (GSH-Px)) and total antioxidant capacity (T-AOC), in addition to decreased level of malondialdehyde (MDA) in CCl4-induced hepatotoxicity study further revealed that CAL exhibited significant hepatoprotective and antioxidant effects. Collectively, these findings present a liposomal formulation with significantly improved oral bioavailability and an increased in vivo antioxidant activity of CA.Download high-res image (143KB)Download full-size image
Co-reporter:Xia Cao, Wenwen Deng, Min Fu, Yuan Zhu, Hongfei Liu, Li Wang, Jin Zeng, Yawei Wei, Ximing Xu, Jiangnan Yu
European Journal of Pharmaceutical Sciences (23 January 2013) Volume 48(Issues 1–2) pp:64-71
Publication Date(Web):23 January 2013
DOI:10.1016/j.ejps.2012.10.012
The objective of this study was to prepare a 72 h-release formulation of silybin (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs). The results of scanning electron microscopy and N2 adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385.89 ± 1.12 m2/g) and a small pore size (2.74 nm on average). The in vitro dissolution profiles of both 72 h-SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08 M) of Na2CO3 solutions revealed that 0.06 M Na2CO3 solution was the optimal medium in which silybin could be released from 72 h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72 h-SLB and silybin-loaded PSNs in beagle dogs were also established. Using 0.06 M Na2CO3 solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs. The findings support the fact that the 72 h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na2CO3 solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.Download high-res image (62KB)Download full-size image
Co-reporter:Hui-Yun Zhang, Wen-Qian Xu, Yuan-Wen Wang, Emmanuel Omari-Siaw, Yan Wang, Yuan-yuan Zheng, Xia Cao, Shan-Shan Tong, Jiang-nan Yu, Xi-ming Xu
International Journal of Pharmaceutics (11 April 2016) Volume 502(Issues 1–2) pp:98-106
Publication Date(Web):11 April 2016
DOI:10.1016/j.ijpharm.2016.02.024
Periplogenin (PPG), a cardiac glycoside prepared from Cortex periplocae, with similar structure to bufalin, has been found to induce apoptosis in many tumor cells. However, lots of cardiac glycosides possessing strong antitumor activity in vitro have still not passed phase I clinical trials, mostly due to poor tumor selectivity and systemic toxicity. To overcome this drawback, we designed octreotide-periplogenin (OCT-PPG) conjugate by coupling PPG–succinate to the amino-terminal end of octreotide. In comparison with free PPG, the conjugate exhibited significantly stronger cytotoxicity on HepG2 cells (SSTRs overexpression) but much less toxicity in L-02 cells. After intravenous injection of OCT-PPG conjugate into H22 tumor-bearing mice, its total accumulation in tumor was 2.3 fold higher than that of free PPG, but was 0.71- and 0.84-fold lower in heart and liver, respectively, suggesting somatostatin-mediated target delivery of PPG into the tumor tissue and reduced distribution in heart and liver. In vivo studies using H22 tumor model in mice confirmed the remarkable therapeutic effect of this conjugate. These results suggested that OCT-PPG conjugate could provide a new approach for clinical application of cardiac glycosides and as a targeting agent for cancer therapy.Download high-res image (165KB)Download full-size image
