Polymersome production on a microfluidic platform using pH sensitive block copolymers

Development of pH sensitive biocompatible block copolymer polymersomes, which are stable in physiological conditions, is enabling the intracellular delivery of water soluble drugs and proteins. As a result, it is becoming increasingly important to develop robust production methods to enhance the polymersome encapsulation efficiency. One way that this could be achieved is through production in microfluidic devices that potentially offer more favourable conditions for encapsulation. Here a flow focussing microfluidic device is used to induce self-assembly of poly(2-(methacryloyloxy)ethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-b-PDPA) block copolymer by changing the pH of the flows within the microchannels. The laminar flow conditions within the device result in a pH gradient at either interface of the central flow, where diffusion of hydrogen ions enables the deprotonation of the PDPA block copolymer and results in self-assembly of polymersomes. Dynamic light scattering reveals hydrodynamic diameters in the range of 75-275 nm and double membrane structures visualized using transmission electron microscopy indicate that polymersome nanostructures are being produced. The encapsulation efficiency for Bovine Serum Albumin (BSA) was calculated by measuring the spectroscopic absorbance at 279 nm and indicates that the encapsulation efficiency produced in the microfluidic device is equivalent to the standard in solution production method. Critically, the microfluidic system eliminates the use of organic solvents, which limit biological applications, through the pH induced self-assembly process and offers a continuous production method for intracellular delivery polymersomes.