Photo-responsive polymer micelles from o-nitrobenzyl ester-based amphiphilic block copolymers synthesized by mechanochemical solid-state copolymerization

Abstract

Polymer micelles with a tunable drug release would be suitable for the concept of drug delivery system. We constructed photo-responsive polymer micelles from amphiphilic block copolymers. The polymer micelles were synthesized by mechanochemical solid-state copolymerization of poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) and 4,5-dimethoxy-2-nitrobenzyl methacrylate as a photosensitive moiety. The above mechanochemical solid-state copolymerization was performed by vibratory-ball milling at 30 Hz in a nitrogen atmosphere with the use of an agate vessel and an agate ball to yield amphiphilic block copolymers (PHPMA-b-PDNMA). Spherical polymer micelles were formed by the self-assembly of PHPMA-b-PDNMA. The diameter of the PHPMA-b-PDNMA micelles was in the range of 130-200 nm. The PHPMA-b-PDNMA micelles loaded with the antitumor drug 5-fluorouracil (5-FU) showed photo irradiation induced time-dependent release of 5-FU with an associated decrease of micellar size. The drug release profile of the PHPMA-b-PDNMA micelles followed a clear sigmoid curve. Our approach provides a controlled drug release system through the use of photo-responsive polymer micelles, accompanied by the gradual decrease of micellar size. Polymer micelles with a tunable drug release are promising carriers for drug delivery system. It is very important to clarify the correlation between micellar dissociation kinetics and drug release profile on a stimuli-induced deformation of polymer micelles. In this study, photo-cleavable o-nitrobenzyl ester-based amphiphilic block copolymer was successfully designed and prepared by mechanochemical solid-state copolymerization without any solvents and initiators. The self-assembled block copolymer micelles containing anticancer drugs showed sigmoidal decrease of micellar size and released the corresponding drugs depending on the photo-irradiation time.