The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies
摘要The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules re-mains a challenge for developing prodrug nanoassemblies.This study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alco-hols as assembly modules(C16,C18,C20,and C24).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules'sensitivity.The extension of the carbon chains improved the prodrugs'self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C20 can balance efficacy and safety.These results provide a great reference for the rational design of prodrug nanoassemblies.
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