Polymersome production on a microfluidic platform using pH sensitive block copolymers

Abstract

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.

From Stealthy Polymersomes and Filomicelles to “Self” Peptide-Nanoparticles for Cancer Therapy

“…Despite growing evidence of immunological responses to PEG (36, 37) that can in principle limit therapeutic efficacy, it remains a widely used hydrophilic polymer in drug formulations. Attractive alternatives include zwitterionic polymers (38) that are just emerging in polymersome applications to tumors (39). …”

Alleviation of capsular formations on silicone implants in rats using biomembrane-mimicking coatings

“…Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) mimics the head group of phosphatidylcholine in the cell membrane and exhibits exceptional anti-protein-adsorption activity, anti-thrombotic activity and hemocompatibility when used in coating materials for coronary stents [20], artificial joints [21], drug delivery carriers [22] and biomicrofluidics [23]. Increased hydrophilicity due to zwitterionic groups and biomembrane-mimicking phosphocholine moieties of PMPC are important contributors to the outstanding biocompatibility exhibited by PMPC-coated materials [24].…”

Microfluidic fabrication of water-in-water (w/w) jets and emulsions

“…At high frequencies (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), the jet appears to be perturbed at a higher frequency than the natural frequency of droplet formation (Figs. 2(i)-2(k)).…”

“…Advances in droplet microfluidics have enabled the generation of emulsions of complex geometry with a high degree of control over drop size and uniformity as well as with improved encapsulation efficiencies. 1,2 These have led to a plethora of novel approaches for fabricating functional materials, 3,4 which includes microgel particles, [5][6][7][8][9] liposomes, [10][11][12][13] polymersomes, [14][15][16][17][18] and colloidosomes. 9,19,20 Most of these approaches involve the use of emulsion drops as templates and these emulsions contain at least one organic solvent as one of the emulsion phases.…”