Synthesis and physicochemical properties of doxorubicin-loaded PEGA containing amphiphilic block polymeric micelles

Abstract

In this study, we aim to synthesize self-assembled amphiphilic diblock poly(PEGA-b-HEA-PCL) copolymers through RAFT living polymerization, targeting the delivery of hydrophobic anticancer drugs. The synthesized self-assembled diblock copolymers polymeric micelles (PMs) comprising poly(ethylene glycol) methyl ether acrylate (PEGA), as a hydrophilic segment and 2-hydroxyethyl acrylate-polyhexanoate monomer (HEA-PCL) with different block lengths, as a hydrophobic segment. The chemical structures, compositions, and self-assembled behavior were identified through ¹H NMR spectroscopy. The thermal stability was assessed through TGA and DSC. Furthermore, DOX was encapsulated into all PMs. The drug-loaded PMs exhibited enhanced drug release profiles in acidic medium. Particle diameter was measured through DLS and TEM techniques. The cell viability of diblock polymers and selected DOX-loaded PMs were evaluated against non-cancerous (L929) and cancerous cells (SK-N-AS), respectively, through well-known MTT assay. Micellar aggregates with mean diameters of approximately 127.2–145.3 nm formed in aqueous solution. The diameters of PMs increased to 141.5–173.1 nm upon the incorporation of DOX. The drug loading content and encapsulation efficiency of PMs were approximately 8.09–18.84% and 30.43–54.07%, respectively. The MTT assay results indicated that all synthesized materials had minimal effects on the viability of L929 cells, while DOX-loaded materials inhibited the viability of neuroblastoma cells by 68.7%. The highest drug release was 89.20% at pH 7.4, while 83.45% at pH 5.0 for 40 h. These findings suggest that the synthesized amphiphilic PMs are promising candidates for drug delivery systems.