Oligo(ethylene glycol) Methacrylate Copolymer-Modified Liposomes for Temperature-Responsive Drug Delivery System

Abstract

A thermoresponsive copolymer based on oligo(ethylene glycol) methacrylate, Chol-P(MEO2MA-co-OEGMA), was synthesized using Atom Transfer Radical Polymerization (ATRP) and incorporated into thermosensitive liposomes (TSLs) for controlled drug release. The copolymer exhibited a lower critical solution temperature (LCST) of 37 °C, making it suitable for biomedical applications requiring precise thermal triggers. The copolymer was incorporated into various TSL formulations alongside phospholipids such as DPPC, Lyso-PC, HSPC, and DSPC. Physicochemical characterization of the liposomes, including average size, polydispersity index, loading efficiency (LE), and encapsulation efficiency (EE), was performed using dynamic light scattering and fluorescence spectroscopy. The results showed that the incorporation of the copolymer slightly affected particle size and decreased LE and EE in most formulations. Lyso-PC-containing formulations exhibited lower LE and EE, likely due to instability during purification. Albumin encapsulation demonstrated lower LE compared to the smaller carboxyfluorescein drug model, highlighting the influence of molecular weight on loading. Although copolymer-modified liposomes showed reduced loading capacity, they enhanced thermoresponsiveness in HSPC-based formulations. These findings suggest that incorporating thermoresponsive polymers into TSLs can optimize drug delivery systems for targeted, thermally triggered release.

Keywords

• thermosensitive liposomes
• thermo-responsive polymers
• drug delivery systems
• nanocarriers
• LCST