Tunable Thermosensitivity of Biodegradable Polymer Micelles of Poly(ε-caprolactone) and Polyphosphoester Block Copolymers

The development of thermoresponsive and biodegradable polymer nanoparticles with tunable thermosensitivity and biocompatibility is of great interest, especially for in vivo biomedical applications. In this study, biodegradable polymer micellar nanoparticles with tunable thermosensitivity are reported. They are based on various biodegradable block copolymers of hydrophobic poly(ε-caprolactone) and thermosensitive polyphosphoesters, obtained through poly(ε-caprolactone)/stannous octoate coinitiated random ring-opening polymerization of cyclic phosphoester monomers. The thermosensitive micellar shells of nanoparticles turn out to be more hydrophobic and result in aggregates in aqueous solution when the temperature is higher than their lower critical solution temperature (LCST). The phase transition temperatures can be adjusted by controlling the molecular weights and the compositions of biodegradable polyphosphoester blocks. Decreased molecular weights of poly(ethyl ethylene phosphate) (PEEP) lead to higher LCST, whereas copolymerization of PEEP with more hydrophobic component results in lower LCST and sharper response. It has also been observed that increased sodium chloride concentration in micelle solution leads to lower responsive temperature. Therefore, the thermosensitivity of micelles can be conveniently adjusted over a wide temperature range. With good biocompatibility and tunable thermosensitivity, these biodegradable polymer-based nanoparticles are potential stimuli-responsive materials for biomedical applications.