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Rupei Tang - One of the best experts on this subject based on the ideXlab platform.
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ph sensitive carboxymethyl chitosan hydrogels via acid labile Ortho Ester linkage as an implantable drug delivery system
Carbohydrate Polymers, 2019Co-Authors: Jialu Gao, Xin Wang, Jun Wang, Guoqing Yan, Yan Zheng, Rupei TangAbstract:Abstract A series of pH-sensitive carboxymethyl chitosan (CMCS) hydrogels were prepared via Ortho Ester linkage. DOX-loaded gelatin nanoparticles with an average diameter of around 50 nm were incorporated into hydrogels to obtain hybrid hydrogels (DOX-NPs-Gel), which could be locally implanted into tumor site in any shape. The physicochemical and mechanical properties of these hydrogels could be easily controlled by adjusting the proportion of crosslinking agent. DOX-NPs-Gel showed the pH-dependent degradation and drug release, and only 29.9% of DOX was released within 144 h at pH 7.4, while the cumulative release reached 49.3% and 65% at pH 6.5 and 5.0, respectively. In vivo study demonstrated that the implanted DOX-NPs-Gel efficiently improved DOX accumulation in tumor site through continuously degradation in mildly acidic environment of tumor tissues, and the tumor volume at the end of experiment was only 81.53 mm3, while tumor size reached to 229.22 mm3 and 174.15 mm3 after intravenous treatment with free DOX and DOX-NPs, respectively.
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carboxymethyl chitosan based nanogels via acid labile Ortho Ester linkages mediated enhanced drug delivery
International Journal of Biological Macromolecules, 2019Co-Authors: Xin Wang, Jun Wang, Guoqing Yan, Panpan Zhang, Rupei TangAbstract:This work described the preparation of two type nanogels based on the crosslinking between carboxymethyl chitosan (CMCS) and two different crosslink agents, an acid-labile cyclic Ortho Ester compound with dual epoxy end groups (OEDe) or corresponding non-sensitive ethyleneglycol diglycidyl ether (EGDE). The particle size, zeta potential, and micromorphology were characterized by dynamic light scattering and electron microscopy, respectively. Nanogels' stability was also investigated at physiological environments. Doxorubicin hydrochloride as a therapeutic drug model was efficiently embedded into nanogels. The pH-triggered size changing, degradation and drug release were then investigated at three different pH values. Cellular uptake and cytotoxicity evaluation demonstrated that NG1/DOX could be successfully degraded and efficiently release DOX in acid cell organelles, leading to higher cytotoxicity than NG2/DOX. The accumulation and penetration of these DOX-loaded nanogel were then investigated by tumor-like multicellular spheroids (MCTS). The results indicated that the acid-degradable nanogels can deliver more DOX into the inner of MCTS by the hydrolysis of Ortho Ester bonds, thus efficiently inhibit the growth of MCTS. All results suggested that the acid-degradable nanogels could be degraded in mildly acidic conditions and remain stable at physiological environment, which indicated that the acid-degradable nanogels would be potentially useful as drug carriers.
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Supplemental material for Acid-labile hyperbranched poly(Ortho Ester amido amine) as efficient gene carriers: Preparation, characterization, and in vitro evaluation
2019Co-Authors: Jun Wang, Xin Wang, Guo Yan, Xiaoli Zeng, Rupei TangAbstract:Supplemental Material for Acid-labile hyperbranched poly(Ortho Ester amido amine) as efficient gene carriers: Preparation, characterization, and in vitro evaluation by Shuting Li, Liefeng Hu, Jun Wang, Guo Yan, Xin Wang, Dapeng Li, Xiaoli Zeng and Rupei Tang in Journal of Biomaterials Applications
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tpgs functionalized and Ortho Ester crosslinked dextran nanogels for enhanced cytotoxicity on multidrug resistant tumor cells
Carbohydrate Polymers, 2018Co-Authors: Min Sun, Xin Wang, Guoqing Yan, Xu Cheng, Rupei TangAbstract:Abstract Herein pH-sensitive nanogels (NG1) and P-glycoprotein-repressive nanogels (NG2) were prepared by copolymerization between an Ortho Ester crosslinker (OEAM) and tocopheryl polyethylene glycol succinate (TPGS)-free or conjugated dextran. Nanogels with or without TPGS possessed a uniform diameter (∼180 nm) and excellent stability in various physiological environments. Doxorubicin (DOX) was successfully loaded into NG1 and NG2 to give NG1/DOX and NG2/DOX, both of them showed appropriate drug release profiles under mildly acidic conditions (pH 5.0). NG2/DOX possessed higher drug enrichment and lethality than NG1/DOX did on MCF-7/ADR cells. Analysis of corresponding index of efflux activity showed that NG2 could induce depolarization of mitochondrial membrane and interfere with ATP metabolism. NG2/DOX also displayed increased penetration and growth inhibition on MCF-7/ADR multicellular spheroids. These results demonstrated that pH-sensitive TPGS-functionalized nanogels (NG2) as drug carriers had great potential to suppress drug efflux in MCF-7/ADR cells and even overcome MDR on cancer cells.
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pH-sensitive amphiphilic triblock copolymers containing Ortho Ester main-chains as efficient drug delivery platforms.
Materials science & engineering. C Materials for biological applications, 2018Co-Authors: Jun Wang, Xin Wang, Yan Huang, Rupei TangAbstract:Abstract Triblock copolymer PEG-block-poly(Ortho Ester urethane)-block-PEG (PEG-POEU-PEG) was conveniently prepared via polycondensation reaction between the Ortho Ester-containing diol and hexamethylene diisocyanate (HDI) at varying reaction time followed by termination with polyethylene glycol monomethyl ether (mPEG). PEG-POEU-PEG could further self-assemble into nano-scaled micelles. Ortho Ester degradation in these micelles was significantly accelerated at pH 5.0 due to its pH sensitivity. In vitro drug release profiles showed that only a small amount of the loaded DOX was released in PBS solution at pH 7.4, while DOX could be quickly released at pH 5.0. MTT assay reveals that the micelles were completely nontoxic to cultured cells. Moreover, DOX-loaded micelles exhibited efficient antitumor efficiency against cancer cells. Therefore, the micelles may be potential drug carriers in cancer therapy.
Robert Gurny - One of the best experts on this subject based on the ideXlab platform.
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ocular biocompatibility of a poly Ortho Ester characterized by autocatalyzed degradation
Journal of Biomedical Materials Research Part A, 2003Co-Authors: Suzanne Einmahl, Jorge Heller, Cyrus Tabatabay, Robert Gurny, Stephanie Ponsart, R A Bejjani, F Dhermies, M Savoldelli, Francine BeharcohenAbstract:The biocompatibility of autocatalyzed poly(Ortho Ester) (POE70LA30), a viscous, hydrophobic, bioerodible polymer, was investigated. POE70LA30 was synthesized, sterilized by gamma irradiation, and injected in rabbit eyes at adequate volumes through subconjunctival, intracameral, intravitreal, and suprachoroidal routes. Clinical examinations were performed postoperatively at regular time points for 6 mo, and histopathologic analysis was carried out to confirm tissular biocompatibility. After subconjunctival injection, the polymer was well tolerated and persisted in the subconjunctival space for about 5 weeks. In the case of intracameral injections, polymer biocompatibility was good; the POE70LA30 bubble was still present in the anterior chamber for up to 6 mo after injection. No major histopathologic anomalies were detected, with the exception of a localized Descemet membrane thickening. After intravitreal administration, POE70LA30 biocompatibility was excellent, and no inflammatory reaction could be detected during the observation period. The polymer was degraded in approximately 3 mo. Suprachoroidal injections of POE70LA30 were reproducible and well tolerated. POE70LA30 triggered a slight elevation of the retina and choroid upon clinical observation. The polymer was detectable in the suprachoroidal space for about 6 mo. No inflammatory reaction and no major retinal anomalies could be detected by histology. In conclusion, POE70LA30 appears to be a promising biomaterial for intraocular application, potentially providing sustained drug delivery over an extended period of time, with a good tolerance. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 44–53, 2003
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control of molecular weight for auto catalyzed poly Ortho Ester obtained by polycondensation reaction
International Journal of Polymer Analysis and Characterization, 2002Co-Authors: K Schwachabdellaoui, Jorge Heller, Robert Gurny, John BarrAbstract:Polycondensation of auto-catalyzed poly(Ortho Ester)s (POE x LA y ) containing lactic acid units in the polymer backbone is described. The use of n-decanol during the polymerization as a chain stopper allows good control of polymer molecular weight. POE 70 LA 30 based on 3,9-diet-hylidene-2,4,8,10-tetraoxaspiro[5.5]undecane (DETOSU), 1,10-decanediol-lactate and 1,10-decanediol and synthesized by using 5, 10 and 15 mol % of n-decanol were characterized by 13 C NMR, 1 H NMR and FT-IR. The thermal and viscoelastic properties of such polymers as well as their molecular weight distribution are also reported.
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Release of BSA from poly(Ortho Ester) extruded thin strands.
Journal of controlled release : official journal of the Controlled Release Society, 2001Co-Authors: Alexandra Rothen-weinhold, Robert Gurny, John Barr, Hui-rong Shen, K. Schwach-abdellaoui, Jorge HellerAbstract:Abstract A solventless procedure was used where powdered polymer and micronized protein were intimately mixed and then extruded into 1 mm strands that were cut to the desired length. The polymers used were poly(Ortho Esters) specifically designed to allow extrusion in the neighborhood of 70°C. At these temperatures many proteins maintain activity in the dry state. In vitro erosion and BSA release results indicate that after a fairly long lag-time, BSA release and polymer erosion occur concomitantly indicating an erosion-controlled process. The lag-time could be eliminated by the addition to the mixture prior to extrusion between 1 and 5 wt% poly(ethylene glycol) or its methoxy derivatives. The lag-time could also be eliminated by using an AB-block copolymer where A is poly(Ortho Ester) and B is poly(ethylene glycol).
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a new poly Ortho Ester based drug delivery system as an adjunct treatment in filtering surgery
Investigative Ophthalmology & Visual Science, 2001Co-Authors: Suzanne Einmahl, Cyrus Tabatabay, F Dhermies, Francine Beharcohen, Serge Rudaz, Gilles Renard, Robert GurnyAbstract:purpose. Pharmacologic modulation of wound healing after glaucoma filtering surgery remains a major clinical challenge in ophthalmology. Poly(Ortho Ester) (POE) is a bioerodible and biocompatible viscous polymer potentially useful as a sustained drug delivery system that allows the frequency of intraocular injections to be reduced. The purpose of this study was to determine the efficacy of POE containing a precise amount of 5-fluorouracil (5-FU) in an experimental model of filtering surgery in the rabbit. methods. Trabeculectomy was performed in pigmented rabbit eyes. An ointmentlike formulation of POE containing 1% wt/wt 5-FU was injected subconjunctivally at the site of surgery, during the procedure. Intraocular pressure (IOP), bleb persistence, and ocular inflammatory reaction were monitored until postoperative day 30. Quantitative analysis of 5-FU was performed in the anterior chamber. Histologic analysis was used to assess the appearance of the filtering fistula and the polymer’s biocompatibility. results. The decrease in IOP from baseline and the persistence of the filtering bleb were significantly more marked in the 5-FU–treated eyes during postoperative days 9 through 28. Corneal toxicity triggered by 5-FU was significantly lower in the group that received 5-FU in POE compared with a 5-FU tamponade. Histopathologic evaluation showed that POE was well tolerated, and no fibrosis occurred in eyes treated with POE containing 5-FU. conclusions. In this rabbit model of trabeculectomy, the formulation based on POE and containing a precise amount of 5-FU reduced IOP and prolonged bleb persistence in a way similar to the conventional method of a 5-FU tamponade, while significantly reducing 5-FU toxicity.
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Protein release from poly(Ortho Ester) extruded rods
Macromolecular Symposia, 2001Co-Authors: Alexandra Rothen-weinhold, Robert Gurny, John Barr, Hui-rong Shen, Jorge HellerAbstract:Poly(Ortho Ester) rods containing 15 wt% FITC-BSA were prepared by extruding an intimate mixture of finely powdered polymer and protein at a temperature where protein activity is retained. After an induction period, linear in vitro release kinetics were obtained with concomitant polymer weight loss.
Jorge Heller - One of the best experts on this subject based on the ideXlab platform.
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polyacetal and poly Ortho Ester poly ethylene glycol graft copolymer thermogels preparation hydrolysis and fitc bsa release studies
Journal of Controlled Release, 2006Co-Authors: Etienne Schacht, Kristin Vandertaelen, Veska Toncheva, Jorge HellerAbstract:Abstract Graft copolymers comprised of a polyacetal backbone with pendant poly(ethylene glycol) side-chains were prepared using a condensation reaction between a divinyl ethers, a diol and Fmoc-protected serinol, followed by deprotecting the amine and reacting the polyacetal with pendant amino groups with PEG-α-methoxy-ω-succimidylcarbonate. A series of materials having lower critical solution temperature (LCST) between 25 and 60 °C has been prepared. Since LCST is determined by the hydrophilic–hydrophobic balance, and this in turn is determined by the molecular weight of the polyacetal backbone, the molecular weight of the grafted PEG and the amount grafted, materials having a desired LCST could be readily prepared. Incorporating FITC-BSA at 1 wt.% into the thermogel resulted in sustained release over about 100 days at pH 7.4 and 40 days at pH 5.5 without a burst and by reasonably linear kinetics. Incorporating FITC-BSA at 5 wt.% into the thermogel significantly increased delivery time at pH 5.5 and decreased the difference in delivery rates between pH 5.5 and pH 7.4. FITC-BSA is released by a predominantly erosion-controlled process and FITC-BSA depletion coincides closely with total gel dissolution. More rapidly eroding thermogels were prepared by replacing the polyacetal backbone with a poly(Ortho Ester) backbone. Such gels completely dissolved between 3 and 6 days. It is hoped that intermediate erosion rates can be achieved by preparing backbones containing both acetal and Ortho Ester linkages. Such materials have been prepared and shown to have LCST values in the desired range, but no erosion, or drug release studies have as yet been completed.
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preparation characterization and in vitro evaluation of physostigmine loaded poly Ortho Ester and poly Ortho Ester poly d l lactide co glycolide blend microspheres fabricated by spray drying
Biomaterials, 2004Co-Authors: Ling Wang, Steve Ng, Chengshu Chaw, Shabbir Moochhala, Bin Zhao, Yi Yan Yang, Jorge HellerAbstract:Abstract The physostigmine-loaded poly(Ortho Ester) (POE), poly( dl -lactide- co -glycolide) (PLGA) and POE/PLGA blend microspheres were fabricated by a spray drying technique. The in vitro degradation of, and physostigmine release from, the microspheres were investigated. SEM analysis showed that the POE and POE/PLGA blend particles were spherical. They were better dispersed when compared to the pure PLGA microspheres. Two glass transition temperature ( T g ) values of the POE/PLGA blend microspheres were observed due to the phase separation of POE and PLGA in the blend system. XPS analysis proved that POE dominated the surfaces of POE/PLGA blend microspheres, indicating that the blend microspheres were coated with POE. The encapsulation efficiencies of all the microspheres were more than 95%. The incorporation of physostigmine reduced the T g value of microspheres. The T g value of the degrading microspheres increased with the release of physostigmine. For instance, POE blank microspheres and physostigmine-loaded POE microspheres had a T g value of 67°C and 48°C, respectively. After 19 days in vitro incubation, T g of the degrading POE microspheres increased to 55°C. Weight loss studies showed that the degradation of the blend microspheres was accelerated with the presence of PLGA because its degradation products catalyzed the degradation of both POE and PLGA. The release rate of physostigmine increased with increase of PLGA content in the blend microspheres. The initial burst release of physostigmine was effectively suppressed by introducing POE to the blend microspheres. However, there was an optimized weight ratio of POE to PLGA (85:15 in weight), below which a high initial burst was induced. The POE/PLGA blend microspheres may make a good drug delivery system.
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Molecularly engineered poly(Ortho Ester) microspheres for enhanced delivery of DNA vaccines.
Nature materials, 2004Co-Authors: Chun Wang, Jorge Heller, Hui-rong Shen, David T. Ting, David P. Nguyen, Jianzhu Chen, Herman N. Eisen, Robert Langer, David PutnamAbstract:Genetic vaccination using plasmid DNA presents a unique opportunity for achieving potent immune responses without the potential limitations of many conventional vaccines. Here we report the design of synthetic biodegradable polymers specifically for enhancing DNA vaccine efficacy in vivo. We molecularly engineered poly(Ortho Ester) microspheres that are non-toxic to cells, protect DNA from degradation, enable uptake by antigen-presenting cells, and release DNA rapidly in response to phagosomal pH. One type of microsphere of poly(Ortho Esters) that releases DNA vaccines in synchrony with the natural development of adaptive immunity, elicited distinct primary and secondary humoral and cellular immune responses in mice, and suppressed the growth of tumour cells bearing a model antigen. This polymer microparticulate system could, with further study, have implications for advancing the clinical utility of DNA vaccines as well as other nucleic-acid-based therapeutics against viral infections and cancer.
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ocular biocompatibility of a poly Ortho Ester characterized by autocatalyzed degradation
Journal of Biomedical Materials Research Part A, 2003Co-Authors: Suzanne Einmahl, Jorge Heller, Cyrus Tabatabay, Robert Gurny, Stephanie Ponsart, R A Bejjani, F Dhermies, M Savoldelli, Francine BeharcohenAbstract:The biocompatibility of autocatalyzed poly(Ortho Ester) (POE70LA30), a viscous, hydrophobic, bioerodible polymer, was investigated. POE70LA30 was synthesized, sterilized by gamma irradiation, and injected in rabbit eyes at adequate volumes through subconjunctival, intracameral, intravitreal, and suprachoroidal routes. Clinical examinations were performed postoperatively at regular time points for 6 mo, and histopathologic analysis was carried out to confirm tissular biocompatibility. After subconjunctival injection, the polymer was well tolerated and persisted in the subconjunctival space for about 5 weeks. In the case of intracameral injections, polymer biocompatibility was good; the POE70LA30 bubble was still present in the anterior chamber for up to 6 mo after injection. No major histopathologic anomalies were detected, with the exception of a localized Descemet membrane thickening. After intravitreal administration, POE70LA30 biocompatibility was excellent, and no inflammatory reaction could be detected during the observation period. The polymer was degraded in approximately 3 mo. Suprachoroidal injections of POE70LA30 were reproducible and well tolerated. POE70LA30 triggered a slight elevation of the retina and choroid upon clinical observation. The polymer was detectable in the suprachoroidal space for about 6 mo. No inflammatory reaction and no major retinal anomalies could be detected by histology. In conclusion, POE70LA30 appears to be a promising biomaterial for intraocular application, potentially providing sustained drug delivery over an extended period of time, with a good tolerance. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 44–53, 2003
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semisolid self catalyzed poly Ortho Ester s as controlled release systems protein release and protein stability issues
Journal of Pharmaceutical Sciences, 2002Co-Authors: Marco Van De Weert, Jorge Heller, Marinus Jacob Van Steenbergen, Jeffrey L Cleland, Wim E Hennink, Daan J A CrommelinAbstract:Abstract Semisolid, self-catalyzed poly(Ortho Ester)s (POEs), are investigated as potential sustained-release systems for proteins. In this study, some factors influencing protein release kinetics and protein instability were evaluated. As model proteins, lysozyme, α-lactalbumin, bovine serum albumin, and vascular endothelial growth factor, which were lyophilized from various buffer solutions in the absence and presence of lyoprotectants, were used. For all protein formulations, the release kinetics followed the visually observed polymer dissolution profile. In the absence of any buffers in the protein formulation, the release was continuous. Formulations containing a buffer below pH 7 accelerated POE degradation, resulting in faster protein release. In contrast, a strong buffer capacity at pH 7 reduced the POE degradation and resulted in a biphasic release pattern. Moreover, proteins with a high isoelectric point (p I >7) appeared to catalyze the POE degradation, and the effect of the buffer strength and pH was much smaller than for proteins with low p I (
Xin Wang - One of the best experts on this subject based on the ideXlab platform.
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ph sensitive carboxymethyl chitosan hydrogels via acid labile Ortho Ester linkage as an implantable drug delivery system
Carbohydrate Polymers, 2019Co-Authors: Jialu Gao, Xin Wang, Jun Wang, Guoqing Yan, Yan Zheng, Rupei TangAbstract:Abstract A series of pH-sensitive carboxymethyl chitosan (CMCS) hydrogels were prepared via Ortho Ester linkage. DOX-loaded gelatin nanoparticles with an average diameter of around 50 nm were incorporated into hydrogels to obtain hybrid hydrogels (DOX-NPs-Gel), which could be locally implanted into tumor site in any shape. The physicochemical and mechanical properties of these hydrogels could be easily controlled by adjusting the proportion of crosslinking agent. DOX-NPs-Gel showed the pH-dependent degradation and drug release, and only 29.9% of DOX was released within 144 h at pH 7.4, while the cumulative release reached 49.3% and 65% at pH 6.5 and 5.0, respectively. In vivo study demonstrated that the implanted DOX-NPs-Gel efficiently improved DOX accumulation in tumor site through continuously degradation in mildly acidic environment of tumor tissues, and the tumor volume at the end of experiment was only 81.53 mm3, while tumor size reached to 229.22 mm3 and 174.15 mm3 after intravenous treatment with free DOX and DOX-NPs, respectively.
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carboxymethyl chitosan based nanogels via acid labile Ortho Ester linkages mediated enhanced drug delivery
International Journal of Biological Macromolecules, 2019Co-Authors: Xin Wang, Jun Wang, Guoqing Yan, Panpan Zhang, Rupei TangAbstract:This work described the preparation of two type nanogels based on the crosslinking between carboxymethyl chitosan (CMCS) and two different crosslink agents, an acid-labile cyclic Ortho Ester compound with dual epoxy end groups (OEDe) or corresponding non-sensitive ethyleneglycol diglycidyl ether (EGDE). The particle size, zeta potential, and micromorphology were characterized by dynamic light scattering and electron microscopy, respectively. Nanogels' stability was also investigated at physiological environments. Doxorubicin hydrochloride as a therapeutic drug model was efficiently embedded into nanogels. The pH-triggered size changing, degradation and drug release were then investigated at three different pH values. Cellular uptake and cytotoxicity evaluation demonstrated that NG1/DOX could be successfully degraded and efficiently release DOX in acid cell organelles, leading to higher cytotoxicity than NG2/DOX. The accumulation and penetration of these DOX-loaded nanogel were then investigated by tumor-like multicellular spheroids (MCTS). The results indicated that the acid-degradable nanogels can deliver more DOX into the inner of MCTS by the hydrolysis of Ortho Ester bonds, thus efficiently inhibit the growth of MCTS. All results suggested that the acid-degradable nanogels could be degraded in mildly acidic conditions and remain stable at physiological environment, which indicated that the acid-degradable nanogels would be potentially useful as drug carriers.
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Supplemental material for Acid-labile hyperbranched poly(Ortho Ester amido amine) as efficient gene carriers: Preparation, characterization, and in vitro evaluation
2019Co-Authors: Jun Wang, Xin Wang, Guo Yan, Xiaoli Zeng, Rupei TangAbstract:Supplemental Material for Acid-labile hyperbranched poly(Ortho Ester amido amine) as efficient gene carriers: Preparation, characterization, and in vitro evaluation by Shuting Li, Liefeng Hu, Jun Wang, Guo Yan, Xin Wang, Dapeng Li, Xiaoli Zeng and Rupei Tang in Journal of Biomaterials Applications
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tpgs functionalized and Ortho Ester crosslinked dextran nanogels for enhanced cytotoxicity on multidrug resistant tumor cells
Carbohydrate Polymers, 2018Co-Authors: Min Sun, Xin Wang, Guoqing Yan, Xu Cheng, Rupei TangAbstract:Abstract Herein pH-sensitive nanogels (NG1) and P-glycoprotein-repressive nanogels (NG2) were prepared by copolymerization between an Ortho Ester crosslinker (OEAM) and tocopheryl polyethylene glycol succinate (TPGS)-free or conjugated dextran. Nanogels with or without TPGS possessed a uniform diameter (∼180 nm) and excellent stability in various physiological environments. Doxorubicin (DOX) was successfully loaded into NG1 and NG2 to give NG1/DOX and NG2/DOX, both of them showed appropriate drug release profiles under mildly acidic conditions (pH 5.0). NG2/DOX possessed higher drug enrichment and lethality than NG1/DOX did on MCF-7/ADR cells. Analysis of corresponding index of efflux activity showed that NG2 could induce depolarization of mitochondrial membrane and interfere with ATP metabolism. NG2/DOX also displayed increased penetration and growth inhibition on MCF-7/ADR multicellular spheroids. These results demonstrated that pH-sensitive TPGS-functionalized nanogels (NG2) as drug carriers had great potential to suppress drug efflux in MCF-7/ADR cells and even overcome MDR on cancer cells.
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pH-sensitive amphiphilic triblock copolymers containing Ortho Ester main-chains as efficient drug delivery platforms.
Materials science & engineering. C Materials for biological applications, 2018Co-Authors: Jun Wang, Xin Wang, Yan Huang, Rupei TangAbstract:Abstract Triblock copolymer PEG-block-poly(Ortho Ester urethane)-block-PEG (PEG-POEU-PEG) was conveniently prepared via polycondensation reaction between the Ortho Ester-containing diol and hexamethylene diisocyanate (HDI) at varying reaction time followed by termination with polyethylene glycol monomethyl ether (mPEG). PEG-POEU-PEG could further self-assemble into nano-scaled micelles. Ortho Ester degradation in these micelles was significantly accelerated at pH 5.0 due to its pH sensitivity. In vitro drug release profiles showed that only a small amount of the loaded DOX was released in PBS solution at pH 7.4, while DOX could be quickly released at pH 5.0. MTT assay reveals that the micelles were completely nontoxic to cultured cells. Moreover, DOX-loaded micelles exhibited efficient antitumor efficiency against cancer cells. Therefore, the micelles may be potential drug carriers in cancer therapy.
Jun Wang - One of the best experts on this subject based on the ideXlab platform.
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ph sensitive carboxymethyl chitosan hydrogels via acid labile Ortho Ester linkage as an implantable drug delivery system
Carbohydrate Polymers, 2019Co-Authors: Jialu Gao, Xin Wang, Jun Wang, Guoqing Yan, Yan Zheng, Rupei TangAbstract:Abstract A series of pH-sensitive carboxymethyl chitosan (CMCS) hydrogels were prepared via Ortho Ester linkage. DOX-loaded gelatin nanoparticles with an average diameter of around 50 nm were incorporated into hydrogels to obtain hybrid hydrogels (DOX-NPs-Gel), which could be locally implanted into tumor site in any shape. The physicochemical and mechanical properties of these hydrogels could be easily controlled by adjusting the proportion of crosslinking agent. DOX-NPs-Gel showed the pH-dependent degradation and drug release, and only 29.9% of DOX was released within 144 h at pH 7.4, while the cumulative release reached 49.3% and 65% at pH 6.5 and 5.0, respectively. In vivo study demonstrated that the implanted DOX-NPs-Gel efficiently improved DOX accumulation in tumor site through continuously degradation in mildly acidic environment of tumor tissues, and the tumor volume at the end of experiment was only 81.53 mm3, while tumor size reached to 229.22 mm3 and 174.15 mm3 after intravenous treatment with free DOX and DOX-NPs, respectively.
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carboxymethyl chitosan based nanogels via acid labile Ortho Ester linkages mediated enhanced drug delivery
International Journal of Biological Macromolecules, 2019Co-Authors: Xin Wang, Jun Wang, Guoqing Yan, Panpan Zhang, Rupei TangAbstract:This work described the preparation of two type nanogels based on the crosslinking between carboxymethyl chitosan (CMCS) and two different crosslink agents, an acid-labile cyclic Ortho Ester compound with dual epoxy end groups (OEDe) or corresponding non-sensitive ethyleneglycol diglycidyl ether (EGDE). The particle size, zeta potential, and micromorphology were characterized by dynamic light scattering and electron microscopy, respectively. Nanogels' stability was also investigated at physiological environments. Doxorubicin hydrochloride as a therapeutic drug model was efficiently embedded into nanogels. The pH-triggered size changing, degradation and drug release were then investigated at three different pH values. Cellular uptake and cytotoxicity evaluation demonstrated that NG1/DOX could be successfully degraded and efficiently release DOX in acid cell organelles, leading to higher cytotoxicity than NG2/DOX. The accumulation and penetration of these DOX-loaded nanogel were then investigated by tumor-like multicellular spheroids (MCTS). The results indicated that the acid-degradable nanogels can deliver more DOX into the inner of MCTS by the hydrolysis of Ortho Ester bonds, thus efficiently inhibit the growth of MCTS. All results suggested that the acid-degradable nanogels could be degraded in mildly acidic conditions and remain stable at physiological environment, which indicated that the acid-degradable nanogels would be potentially useful as drug carriers.
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Supplemental material for Acid-labile hyperbranched poly(Ortho Ester amido amine) as efficient gene carriers: Preparation, characterization, and in vitro evaluation
2019Co-Authors: Jun Wang, Xin Wang, Guo Yan, Xiaoli Zeng, Rupei TangAbstract:Supplemental Material for Acid-labile hyperbranched poly(Ortho Ester amido amine) as efficient gene carriers: Preparation, characterization, and in vitro evaluation by Shuting Li, Liefeng Hu, Jun Wang, Guo Yan, Xin Wang, Dapeng Li, Xiaoli Zeng and Rupei Tang in Journal of Biomaterials Applications
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pH-sensitive amphiphilic triblock copolymers containing Ortho Ester main-chains as efficient drug delivery platforms.
Materials science & engineering. C Materials for biological applications, 2018Co-Authors: Jun Wang, Xin Wang, Yan Huang, Rupei TangAbstract:Abstract Triblock copolymer PEG-block-poly(Ortho Ester urethane)-block-PEG (PEG-POEU-PEG) was conveniently prepared via polycondensation reaction between the Ortho Ester-containing diol and hexamethylene diisocyanate (HDI) at varying reaction time followed by termination with polyethylene glycol monomethyl ether (mPEG). PEG-POEU-PEG could further self-assemble into nano-scaled micelles. Ortho Ester degradation in these micelles was significantly accelerated at pH 5.0 due to its pH sensitivity. In vitro drug release profiles showed that only a small amount of the loaded DOX was released in PBS solution at pH 7.4, while DOX could be quickly released at pH 5.0. MTT assay reveals that the micelles were completely nontoxic to cultured cells. Moreover, DOX-loaded micelles exhibited efficient antitumor efficiency against cancer cells. Therefore, the micelles may be potential drug carriers in cancer therapy.
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Dual-stimuli-sensitive poly(Ortho Ester disulfide urethanes)-based nanospheres with rapid intracellular drug release for enhanced chemotherapy
Science China Chemistry, 2018Co-Authors: Yan Huang, Xin Wang, Jun Wang, Guoqing Yan, Jiejie Qin, Rupei TangAbstract:Herein, new poly(Ortho Ester disulfide urethanes) (POEDU) and poly(Ortho Ester urethanes) (POEU) were successfully synthesized via polycondensation between active Esters of 1,6-hexandiol (HD) and dual-stimuli-sensitive Ortho Ester disulfide diamine or pH-senstive Ortho Ester diamine. The corresponding POEDU and POEU nanospheres were easily fabricated using an oil-in-water emulsion technique. In vitro degradation experiments indicated that POEDU nanospheres degraded faster than POEU nanospheres in mildly acidic and reductive environments. Doxorubicin (DOX) as a model antitumor drug was successfully incorporated into these nanospheres to give DOX-loaded nanoparticles (POEDU-DOX and POEU-DOX). In vitro drug release studies showed that release of DOX from dual-stimuli-sensitive POEDU-DOX was accelerated compared with release from the pH-sensitive POEU-DOX under DL-dithiothreitol (DTT) and mildly acidic conditions. In addition, in vitro uptake and cytotoxicity assays revealed that POEDU-DOX exhibited more efficient antitumor effect than POEU-DOX did against both two-dimensional (2D) cells and three-dimensional (3D) multicellular tumor spheroids (MCTS). Finally, in a mice H22 tumor model, POEDU-DOX exhibited preferable antitumor capability. In conclusion, the pH and redox dual-stimuli-sensitive POEDU nanospheres can be superior drug carriers for cancer treatment.