Fabrication of Core-Crosslinked Polymer Micelles via Photoinduced Azide Crosslinking

Abstract

Polymer micelles have shown significant promise as drug delivery systems, particularly for poorly water-soluble chemotherapeutic agents such as doxorubicin (DOX). However, their instability in biological environments and the potential for easy drug release remain major challenges. This study investigates the fabrication of core-crosslinked polymer micelles using photoinduced azide crosslinking to enhance stability and achieve controlled drug release. Amphiphilic copolymers are synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, incorporating poly(ethylene glycol) methyl ether (PEG) as the hydrophilic block and a styrene-based azide monomer for the hydrophobic core. The micelles are crosslinked via photoinduced azide crosslinking and characterized for size, morphology, and drug loading capacity (DLC). DOX-loaded micelles demonstrated pH-responsive release, with minimal release at physiological pH (7.4) due to strong π–π stacking interactions between DOX and the hydrophobic core. At acidic pH (5), these interactions weakened, resulting in enhanced drug release, mimicking the conditions of the tumor microenvironment. Core-crosslinked micelles exhibited superior stability, reduced drug leakage, and improved release control compared to non-crosslinked micelles. These results highlight the potential of photo-crosslinked polymer micelles as a robust platform for the delivery of hydrophobic anticancer drugs, addressing key limitations of conventional micelle-based systems.