Ketal core cross-linked micelles for pH-triggered release of doxorubicin

Abstract

A ketal core cross-linked (CCL) micelle system of block copolymers of poly(oligo(ethylene glycol) methyl ether methacrylate)-b-poly(styrene-alt-maleic anhydride)-b-poly(styrene) (POEGMA-b-PSMA-b-PS) was prepared by the combination of the reversible addition-fragmentation chain transfer (RAFT) polymerization and amidation process. Doxorubincin (DOX), a model anticancer drug, was loaded into block copolymer micelles with POEGMA segment as hydrophilic corona and PSMA-b-PS block as hydrophobic core. Then core cross-linking was carried out by amidation reaction between maleic anhydride moiety and difunctional amino cross-linker bearing an acid cleavable bond (ketal). The ketal CCL micelles illustrated good stability under physiological condition but disassociated rapidly under acidic pH conditions. TEM images presented spherical shape of CCL micelles with average hydrodynamic diameter at around 45 nm. The DOX release experiments demonstrated a rapid DOX release at pH 5.0 compared to pH 7.4.