Dynamic Metastable Polymersomes: Towards Continuous Flow Manufacturing

Abstract Polymersomes are polymeric analogues of liposomes with exceptional physical and chemical properties. Despite being dubbed as next-generation vesicles since their inception nearly three decades ago, polymersomes have yet to experience translation into the clinical or industrial settings. This is due to a lack of reliable methods to upscale production without compromising control over polymersome properties. Herein we report a continuous flow methodology capable of producing near-monodisperse polymersomes at scale (≥3 g/h) with the unprecedented option of performing downstream polymersome manipulation. Unlike conventional polymersomes, our polymersomes exhibit metastability under ambient conditions, persisting for a lifetime of ca. 7 days, during which polymersome growth occurs until a dynamic equilibrium state is reached. We demonstrate how this metastable state is key to the implementation of downstream processes to e.g., manipulate polymersome size and/or shape in the same continuous stream. The methodology operates in a plug-and-play fashion and is applicable to various block copolymers.