Nanomicelle with long-term circulation and enhanced stability of camptothecin based on mPEGylated α,β-poly (l-aspartic acid)-camptothecin conjugate

To enhance the stability and long-term circulation of camptothecin (CPT), mPEGylated α,β-poly (l-aspartic acid)-CPT conjugates were synthesized, and used to fabricate nanomicelle. Firstly, α,β-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-N3) and azide-terminated poly (ethylene glycol) methyl ether (mPEG-N3) 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 °C for 60 days, and improved the stability of CPT lactone form in aqueous media. A steady release rate of CPT was kept for 72 h, suggested the great potential of mPEG-graft-PAA-CPT nanomicelles as polymer prodrug of CPT.