Self-Assembly of PEG- b -PDLLA and PEG- b -PLGA Nanosized Polymersomes through Chain Mobility and Kinetic Control

While polymersomes hold great promise as innovative drug delivery systems, their formulation is often hindered by the inherent complexity of self-assembly, where the competition between thermodynamically favored structures and kinetically trapped nonequilibrium states makes it particularly challenging to obtain homogeneous vesicle populations. We here report a robust and reproducible formulation method for the preparation of biodegradable polymersomes from PEG- b -PDLLA and PEG- b -PLGA block copolymers. By systematically varying solvent quality, water content and temperature, we demonstrate a sphere-to-worm-to-vesicle transition and how chain mobility and kinetic barriers dictate the self-assembly pathway from micelles to polymersomes. We thus establish a simple formulation strategy by finely balancing solvent quality and temperature to produce monodisperse, nanosized and dynamically stable polymersomes with a tunable membrane thickness. The incorporation of glycolide units further provides control over hydrolytic degradation while preserving the vesicle formation. Overall, this study establishes a rational framework for designing biodegradable polymersomes with predictable structural properties, reinforcing their potential for advanced nanomedicine applications.