Redox-responsive molecular gels based on camptothecin prodrug with disulfide linkage for controlled and sustained drug release

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 mPEG-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 HeLa cells.