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.

Thermoreversibly Assembled Polymersomes for Highly Efficient Loading, Processing, and Delivery of Protein and siRNA Biologics

“…16 Furthermore, the high solids content remains a highly attractive feature of our system, as current polymer and lipid nanoparticle technologies rely on further processing for concentration of suspensions in order to achieve a robust biological response. 41 As a result, our materials can simply be diluted for biological applications without needing further processing.…”

“…31,40 Previous attempts to achieve this rely on complex synthetic or processing approaches, such as polymerization-induced self-assembly (PISA), microfluidic devices, or flash nanoprecipitation (FNP), which require specialized reactors for scale-up and complex manipulations that present challenges for translation to the clinic. 41 Our PSs consisting of BCP blends without mannosylated polymer, TxM0, encapsulate 75-90% of dissolved protein (here, the model protein OVA) in solution as determined by gel electrophoresis, with increased efficiency using higher weight percent of charged polymer ("x" from 33 to 100). (Fig.…”