Fabrication of Core-Crosslinked Polymer Micelles via Photoinduced Azide Crosslinking

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 pi-pi 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.