Thermoresponsive functionalized polymersomes in continuous flow

Functionalized polymersomes are of great interest due to their versatility and wide range of applications in biomedicine. Moreover, addition of specific moieties to the hydrophilic end of the copolymer enables the production of stimuli responsive polymersomes. In this work, thermoresponsive functionalized polymersomes monodispersed in size were produced in continuous flow using a Y-micromixer. A poly[(lactic-co-glycolic acid)-b-poly(ethylene glycol)] (PLGA-b-PEG) block copolymer was functionalized with furan and maleimide derivatives with the aim of studying their reversible aggregation behavior in response to temperature variations. This behavior is associated with the formation of Diels-Alder (DA) adducts at the polymersomes’ interface. Furthermore, temperature’s effect on polymersomes’ size and morphology was studied at different temperatures over time. This study provides a simple method to produce functionalized polymersomes and investigates polymersomes’ response to temperature variations in terms of aggregation/disaggregation and morphological changes related to osmotic pressure imbalance. It was observed that adduct formation between furan- and maleimide-functionalized polymersomes (aggregation) at 25 °C occurred in the first 6 h of reaction. In addition, up to 90 % of adducts were separated during the retro-DA reaction (adduct separation) carried out at 40 °C. Finally, it was found that this type of reaction is also impacted by the polymersomes’ membrane reorganization caused by osmotic pressure imbalance.