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 $d{D}^{-1}$ ≥0.65 in an unbaffled stirred-tank reactor led to a narrow particle size distribution when providing a Froude number of $Fr$ = 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.