Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficac...Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80～120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.展开更多
In past decades, alginate-based multilayer microcapsules have been given important attention in various pharmaceutical investigations. Alginate-poly l lysine-alginate(APA) is studied the most. Due to the similarity be...In past decades, alginate-based multilayer microcapsules have been given important attention in various pharmaceutical investigations. Alginate-poly l lysine-alginate(APA) is studied the most. Due to the similarity between the structure of polyethyleneimine(PEI) and poly-L-lysine(PLL) and also lower price of PEI than PLL, this study was conducted to compare the efficacy of linear(LPEI) and branch(BPEI) forms of PEI with PLL as covering layers in fabrication of microcapsules. The microcapsules were fabricated using electrostatic bead generator and their shape/size, surface roughness, mechanical strength, and interlayer interactions were also investigated using optical microscopy, AFM, explosion test and FTIR, respectively. Furthermore, cytotoxicity was evaluated by comparing the two anionic final covering layers alginate(Alg) and sodium cellulose sulphate(NCS) using MTT test. BPEI was excluded from the rest of the study due to its less capacity to strengthen the microcapsules and also the aggregation of the resultant alginate-BPEI-alginate microcapsules, while LPEI showed properties similar to PLL. MTT test also showed that NCS has no superiority over Alg as final covering layer. Therefore, it is concluded that, LPEI could be considered as a more cost effective alternative to PLL and a promising subject for future studies.展开更多
A novel synthetic strategy towards pH-responsive aggregation-induced emission (AIE)-active tetraphenylethene (TPE)- functionalized polyethylene-based block copolymers is presented. Tris(3-(4-(l,2,2-triphenylvinyl)phen...A novel synthetic strategy towards pH-responsive aggregation-induced emission (AIE)-active tetraphenylethene (TPE)- functionalized polyethylene-based block copolymers is presented. Tris(3-(4-(l,2,2-triphenylvinyl)phenoxy)propyl)borane was used to initiate the polyhomologation of dimethylsulfoxonium methylide to afford well-defined a-TPE-ω-OH linear polyethylenes (PE). The terminal hydroxyl groups were transformed to atom transfer radical polymerization (ATRP) initiating sites by esterification with bromoisobutyryl bromide, followed by polymerization of rert-butyl acrylate (tBA) to provide TPE-PE-b-PtBA block copolymers. After hydrolysis of the rBu group to COOH group, the corresponding pH-responsive TPE-PE-b-PAA block copolymers were obtained. All synthesized block copolymers revealed AIE behavior either in solution or bulk. Due to the pH-responsivity of PAA chains, the aggregation state at different pH and consequently the fluorescence intensity changed. Also, the synthesized block copolymers exhibited ion-specificity fluorescence properties.展开更多
Microspheres containing an antimetabolite drug 5-Fluorouracil were prepared from (poly(lactic) acide)(PLA) or poly(lactic acid)-polyethylene glycol(PLA-PEG) as the carrier by using a water-in-oil-in-water emulsion sol...Microspheres containing an antimetabolite drug 5-Fluorouracil were prepared from (poly(lactic) acide)(PLA) or poly(lactic acid)-polyethylene glycol(PLA-PEG) as the carrier by using a water-in-oil-in-water emulsion solvent evaporation technique. The conditions of the microspheres preparation such as polymer concentration in organic solvent, relative molecular weight of PLA-PEG and PLA/PEG mass ratio were discussed. The surface morphology and the size of the microspheres were observed by SEM. The drug content of microspheres was examined by TGA and the drug release in vitro was evaluated. According to the results, the drug content increased with the nano-silica used. The highest drug content in this study was 39.9%. The drug-release kinetics satisfied the requirements of controlled drug-release.展开更多
基金supported by National Natural Science Foundation of China (No. 51373168)
文摘Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80～120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.
基金This study was fully funded and supported by Shahid Beheshti University of Medical Sciences(Research grant number.7026)The authors would like to acknowledge Mr.F.Rafraf and Mr.S.M.Foroutanfar for their valuable supports in design of encapsulator device and the graphical parts of this project.
文摘In past decades, alginate-based multilayer microcapsules have been given important attention in various pharmaceutical investigations. Alginate-poly l lysine-alginate(APA) is studied the most. Due to the similarity between the structure of polyethyleneimine(PEI) and poly-L-lysine(PLL) and also lower price of PEI than PLL, this study was conducted to compare the efficacy of linear(LPEI) and branch(BPEI) forms of PEI with PLL as covering layers in fabrication of microcapsules. The microcapsules were fabricated using electrostatic bead generator and their shape/size, surface roughness, mechanical strength, and interlayer interactions were also investigated using optical microscopy, AFM, explosion test and FTIR, respectively. Furthermore, cytotoxicity was evaluated by comparing the two anionic final covering layers alginate(Alg) and sodium cellulose sulphate(NCS) using MTT test. BPEI was excluded from the rest of the study due to its less capacity to strengthen the microcapsules and also the aggregation of the resultant alginate-BPEI-alginate microcapsules, while LPEI showed properties similar to PLL. MTT test also showed that NCS has no superiority over Alg as final covering layer. Therefore, it is concluded that, LPEI could be considered as a more cost effective alternative to PLL and a promising subject for future studies.
基金supported by King Abdullah University of Science and Technology (KAUST)
文摘A novel synthetic strategy towards pH-responsive aggregation-induced emission (AIE)-active tetraphenylethene (TPE)- functionalized polyethylene-based block copolymers is presented. Tris(3-(4-(l,2,2-triphenylvinyl)phenoxy)propyl)borane was used to initiate the polyhomologation of dimethylsulfoxonium methylide to afford well-defined a-TPE-ω-OH linear polyethylenes (PE). The terminal hydroxyl groups were transformed to atom transfer radical polymerization (ATRP) initiating sites by esterification with bromoisobutyryl bromide, followed by polymerization of rert-butyl acrylate (tBA) to provide TPE-PE-b-PtBA block copolymers. After hydrolysis of the rBu group to COOH group, the corresponding pH-responsive TPE-PE-b-PAA block copolymers were obtained. All synthesized block copolymers revealed AIE behavior either in solution or bulk. Due to the pH-responsivity of PAA chains, the aggregation state at different pH and consequently the fluorescence intensity changed. Also, the synthesized block copolymers exhibited ion-specificity fluorescence properties.
文摘Microspheres containing an antimetabolite drug 5-Fluorouracil were prepared from (poly(lactic) acide)(PLA) or poly(lactic acid)-polyethylene glycol(PLA-PEG) as the carrier by using a water-in-oil-in-water emulsion solvent evaporation technique. The conditions of the microspheres preparation such as polymer concentration in organic solvent, relative molecular weight of PLA-PEG and PLA/PEG mass ratio were discussed. The surface morphology and the size of the microspheres were observed by SEM. The drug content of microspheres was examined by TGA and the drug release in vitro was evaluated. According to the results, the drug content increased with the nano-silica used. The highest drug content in this study was 39.9%. The drug-release kinetics satisfied the requirements of controlled drug-release.
