Polymersomes for biotechnological applications: Large-scale production of nano-scale vesicles
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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 math-equation-construct">mage="true" class="math-equation-image">mathml="true" class="math-equation-mathml" style="display:none"><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mrow xmlns:w="http://www.wiley.com/namespaces/wiley" xmlns:wiley="http://www.wiley.com/namespaces/wiley/wiley" xmlns:cr="urn://wiley-online-library/content/render" xmlns="http://www.w3.org/1998/Math/MathML"><mi>dmi><mspace width="0.33em">mspace><msup><mi>Dmi><mrow><mo>−mo><mn>1mn>mrow>msup>mrow>mml:math>≥0.65 in an unbaffled stirred-tank reactor led to a narrow particle size distribution when providing a Froude number of math-equation-construct">mage="true" class="math-equation-image">mathml="true" class="math-equation-mathml" style="display:none"><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mrow xmlns:w="http://www.wiley.com/namespaces/wiley" xmlns:wiley="http://www.wiley.com/namespaces/wiley/wiley" xmlns:cr="urn://wiley-online-library/content/render" xmlns="http://www.w3.org/1998/Math/MathML"><mi>Fmi><mi>rmi><mspace width="0.33em">mspace>mrow>mml:math>= 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.

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