To enhance the stability and long-term circulation of camptothecin (CPT), mPEGylated alpha,beta-poly (L-aspartic acid)-CPT conjugates were synthesized, and used to fabricate nanomicelle. Firstly, alpha,beta-poly (L-aspartic acid) derivative (PAA-der) containing alkyne groups was synthesized via the ring-opening of PSI with propargyl amine. And then, azide-functionalized CPT derivatives (CPT-N(3)) and azide-terminated poly (ethylene glycol) methyl ether (mPEG-N(3)) were conjugated with PAA-der by click cycloaddition to give mPEG-graft-PAA-CPT conjugates. The formation of mPEG-graft-PAA-CPT nanomicelles was confirmed by fluorescence spectrophotoscopy and particle size measurements. It was found that all the nanomicelles showed spherical shapes with size about 178 nm. MPEG-graft-PAA-CPT nanomicelles showed good storage stability, even incubation at 37 degrees C for 60 days, and improved the stability of CPT lactone form in aqueous media. A steady release rate of CPT was kept for 72h, suggested the great potential of mPEG-graft-PAA-CPT nanomicelles as polymer prodrug of CPT.
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