Amphiphilic block versus random copolymer nanoparticles with reactive oxygen species responsiveness as berberine...

A series of amphiphilic block and random copolymers based on phenylboronic acid pinacol ester were synthesized via reversible addition-fragmentation chain transfer polymerization. The obtained copolymers can self-assemble in aqueous solution into stable block copolymer nanoparticles and random nanoparticles with sizes of 116.1-158.6 and 126.3-187.0 nm, respectively. All nanoparticles showed hydrogen peroxide (H₂O₂) sensitivity, and the random copolymer nanoparticles presented faster responsiveness to H₂O₂ than did those derived from block copolymers. Berberine (BBR) can be effectively encapsulated into block and random copolymer nanoparticles with loading capacity of 7.6%-9.1% and 7.3%-8.9%, respectively. The BBR release can be controlled in an H₂O₂ medium. For the random copolymer nanoparticles, the release rate of BBR was faster and the cumulative release amounts in response to H₂O₂ were higher over 48 h. The BBR cumulative release amount in the H₂O₂ medium for the block and random copolymer nanoparticles was 62.2%-70.2% and 68.6%-80.4%, respectively. Moreover, good biocompatibility was observed for the BBR-loaded block and random copolymer nanoparticles. BBR and BBR-loaded nanoparticles can improve Glut4 translocation to the cell membrane and promote glucose transport into cells. BBR-loaded nanoparticles can decrease the blood glucose levels in diabetic rats over 15 days. These results imply that the different chain formulation of block and random copolymers affects the H₂O₂ responsiveness and that the two kinds of nanoparticles exhibit potential application as novel vehicles for BBR delivery to regulate blood glucose levels.