Polymersomes for biotechnological applications: Large‐scale production of nano‐scale vesicles

Polymersomes have some fundamental advantages compared to their liposomal counterparts. Due to the increased stability of the polymeric membrane, polymersomes are intended to be reasonably applicable as carrier‐systems and universal reaction compartments for diverse medical and biotechnological applications. Regardless of the application area, suitable methods to produce large vesicle quantities in a controlled and cost‐effective manner have to be developed to put polymersome technology into action at the industrial scale. In this work, the amphiphilic triblock copolymer poly(2‐methyloxazoline) 15 ‐poly(dimethylsiloxane) 68 ‐poly(2‐methyloxazoline) 15 was formed into uniform polymersomes. A recently established production process, based on the use of miniaturized stirred‐tank reactors at the milliliter‐scale (12 mL), was successfully scaled‐up to the liter‐scale (1.5 L) based on solid process engineering parameters. Dynamic light scattering measurements show that using standard propeller stirrers with a dimensionless diameter dD − 1≥0.65 in an unbaffled stirred‐tank reactor led to a narrow particle size distribution when providing a Froude number of F r= 6.52 at the same time. Polymersomes with a mean diameter of 180 nm and a low polydispersity index (PDI<0.2) were generated within about 1 h in one single production step. Thus, this work provides the fundamental basis for further scale‐up purposes, regarding polymersome production in stirred‐tank reactors at the industrial scale.