Cholesterol-Functionalized Porous PLA Microparticles for Enhanced Drug Delivery

A drug delivery platform based on highly porous poly(lactic acid) (PLA) microparticles functionalized with amphiphilic poly(ethylene glycol)-cholesterol (PEG-Chol) has been developed and successfully validated in vitro. This hybrid system addresses key limitations of conventional PLA and poly(lactide-co-glycolide) (PLGA) nanoparticles, providing better encapsulation and sustained drug release. The incorporation of PEG-Chol provides both enhanced aqueous dispersibility for prolonged circulation and membrane-anchoring capabilities, thereby promoting cellular interaction and endocytosis. The particles were loaded with two lipophilic anticancer agents, curcumin (Cur) and tamoxifen (Tmx), whose clinical use is constrained by poor solubility and systemic side effects. In vitro studies using MCF-7 breast cancer cells demonstrated successful cellular uptake and significantly reduced cell viability, validating the therapeutic potential of the system. These results highlight the promise of lipid-functionalized porous PLA particles as a versatile and effective platform for advanced drug delivery in breast cancer treatment.