Development of Micellar Novel Drug Carrier Utilizing Temperature-Sensitive Block Copolymers Containing Cyclodextrin Moieties

Abstract

A drug-delivery system for albendazole (ABZ) based on β-cyclodextrin has been synthesized. Well-defined statistical copolymers, composed of N-isopropylacrylamide (NIPAAM) and trimethylsilylpropargyl acrylate (TMSPA), have been prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. The reactivity ratios were determined to be rTMSPA = 1.12 and rNIPAAm = 0.49, in the absence of RAFT agent, and rTMSPA = 1.35 and rNIPAAm = 0.35, in the presence of RAFT agent using the average of different techniques. Block copolymers were prepared using a POEGMEA40 macro-RAFT agent chain extended with NIPAAm and TMSPA in various feed ratios. After deprotection, the polymers were reacted with 6I-azido-6I-deoxy-β-cyclodextrin via Huisgen azide–alkyne 1,3-dipolar cycloaddition, resulting in thermo-responsive block copolymers with pendant β-cyclodextrin groups, which were then acetylated to modify the polarity and inclusion-complex formation of β-cyclodextrin with the drug albendazole (ABZ). Only block...