Synthesis, self-assembly and thermoresponsive behavior of Poly (lactide-co-glycolide)-b-Poly(ethylene glycol)-b-Poly(lactide-co-glycolide) copolymer in aqueous solution

Thermoresponsive block copolymer (BCP) micelles have attracted increasing attentions due to their potential in biological applications. Many studies have investigated facile strategies to tune the cloud point (Tcp) of thermoresponsive polymer, such as changing hydrophobic/hydrophilic block ratio, micelle concentration and addition of salt. Considering the dependence of properties and functions of BCPs on thermal-induced structural transition, it is necessary to understand the universal mechanism of structural changes during temperatureinduced phase transition; whereas it is challenging to achieve precise structure and properties of BCP micelles with Tcp changes. Herein, we choose thermoresponsive poly (L-lactide-co-glycolide)-poly (ethylene glycol)-poly (L-lactide-co-glycolide) (PLGA-PEG-PLGA) block copolymer as a model system and utilize synchrotron-radiation small-angle X-ray scattering (SAXS) technique to systematically investigate the assembled structure of PLGAPEG-PLGA and the mechanism for thermally induced structural transition of BCP micelle. With the increase of PLGA hydrophobic block, the Tcp significantly decreases, ascribed to the enhancement of the core size, aggregation number, as well as the packing density of PLGA in micelle core. Moreover, the increase of micelle concentration and the addition of salt also decreases the Tcp. Furthermore, temperature-induced drug release is also investigated, the release rate is much faster at above Tcp.