Redox-Responsive Molecular Gels Based on Camptothecin Prodrug with Disulfide Linkage for Controlled

来源 :Wuhan University Journal of Natural Sciences | 被引量 : 0次 | 上传用户:Rang3r
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A novel camptothecin(CPT) prodrug was successfully synthesized by conjugating CPT to adamantanecarboxylic acid(AD) via a cleavable disulfide linkage. The resulting CPT-ss-AD prodrug could act as a low molecular weight gelator to form molecular gels in water/water-miscible organic solvent mixture. Meanwhile, biodegradable amphiphilic block copolymer m PEG-b-P(MAC-co-DTC)(PPMD) was also employed as an organic framework together with CPT-ss-AD to form gel structure. CPT-ss-AD/PPMD gel exhibited less compact molecular arrangement but much more stability than CPT-ss-AD gel. The two kinds of gels could effectively release the original CPT under reductive condition at a near-constant rate without any initial burst. As compared to CPT-ss-AD single-component gel, the two-component gel, CPT-ss-AD/PPMD, had a significantly higher release rate of CPT, while 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide(MTT) assays also indicated highly potent cytotoxic activity against He La cells. A novel camptothecin (CPT) prodrug was successfully synthesized by conjugating CPT to adamantanecarboxylic acid (AD) via a cleavable disulfide linkage. The resulting CPT-ss-AD prodrug could act as a low molecular weight gelator to form molecular gels in water / water- The copolymer of PEG-bP (MAC-co-DTC) (PPMD) was also employed as an organic framework together with CPT-ss-AD to form gel structure. CPT-ss- AD / PPMD gel loaded less compact molecular arrangement but much more stability than CPT-ss-AD gel. The two kinds of gels could effectively release the original CPT under reductive condition at a near-constant rate without any initial burst. As compared to CPT-ss -AD single-component gel, the two-component gel, CPT-ss-AD / PPMD, had a significantly higher rate of release of CPT, while 3- [4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide (MTT) assays also indicated highly potent cytotoxic activity against He La cells.
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