Preparation and optimization of biodegradable star-block copolymer micelles for temperature-triggered drug release

Abstract

Biodegradable and thermoresponsive star-block copolymer micelles were prepared and optimized for temperature-triggered drug release. The star-block poly(ε-caprolactone)-block-poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate) with lower critical solution temperature (LCST) of 42.8°C was chosen to self-assemble into micelles for doxorubicin (DOX) loading. For comparison, the non-thermoresponsive star-block poly(ε-caprolactone)-block-poly(ethylene glycol) micelles with similar composition and diameter were also used to load DOX. The thermoresponsive micelles exhibit an excellent temperature-triggered drug release behavior and pulsed response to the temperature switching between 25°C (below the LCST) and 45°C (above the LCST). The cytotoxicity assay confirmed the effective growth inhibition for HepG2 cells induced by DOX-loaded thermoresponsive micelles, while the blank micelles had low cytotoxicity and good biocompatibility. The confocal laser scanning microscopy suggested that the DOX-loaded micelles could internalize into cytoplasm and cell nucleus of HepG2 cells. The thermoresponsive star-block copolymer micelles can potentially be used in the controlled drug delivery applications.