Making PEG-based Microparticles for Applications in Biology and Medicine
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Making PEG-based Microparticles for Applications in Biology and Medicine Tom O McDonald1, S¯ren Christensen2, and Rein V Ulijn1 1 School of Materials, University of Manchester, Materials Science Centre, Grosvenor Street, Manchester, M1 7HS, United Kingdom 2 VersaMatrix A/S, VersaMatrix A/S, Gamle Carlsberg Vej 10, DK-2500 Valby, Copenhagen, Denmark ABSTRACT We demonstrate the polymerisation of PEGA hydrogel microparticles with a mean diameter of 16 µm (similar to that of biological cells), and we show that these particles are compatible with enzymes. Furthermore, we demonstrate that enzyme catalysed reactions occur faster with these microparticles than with commercially available macrobeads which are typically 200-400 µm in diameter. INTRODUCTION Polyethyleneglycol acrylamide (PEGA) is a polymer hydrogel that is compatible with both aqueous and organic solvents allowing easy chemical modification through solid phase peptide synthesis [1]. Numerous studies have demonstrated that PEGA is also enzyme compatible [2,3]. Its high PEG content prevents non-specific protein absorption and its gel-like matrix facilitates fast diffusion of biomolecules through the polymer. Several workers have shown that PEGA is accessible to small enzymes and that enzyme activity can occur inside the resin [4-6]. It has also been published that reactions between enzymes and on PEGA give near complete conversion with cleavage occurring at expected sites [7]. This combination makes PEGA an ideal material for use as the base for an enzyme responsive drug delivery system based on peptides. Our group has so far demonstrated an enzyme-responsive system based on PEGA particles with coupled peptides, this system has been shown to selectively respond to proteases to either collapse (for selective entrapment) [8] or swell (for delivery) [9]. PEGA particles are currently commercially available between the 200-400 µm in diameter. By developing smaller (biological cell sized) particles there are a number of further applications, such as the potential for drug delivery through release into the circulation [10], or possible use in an automated cell sorted. Also particles with smaller diameters should offer faster enzyme kinetics due to their greater surface area to volume ratio, in the responsive system this would lead to shorter response times.
EXPERIMENT A stainless steel baffle-less reactor (250 ml vol) stirred with an anchor-style agitator was used for the polymerisation reactions. 3.14 g of the PEGA 800 macromonomers (kindly supplied by Versamatrix) was dissolved in 10 ml of distilled water and purged for 30 minutes with N2 gas. 50 ml of Isopar M (isoparaffin) was added to the reactor and was also purged for 30 minutes. The reactor was heated to 70∞C. After 20 minutes of purging 0.16 ml of TEMED (N,N,N ,N ′
′
tetramethylethylenediamine) was added to the oil phase, and 0.156 g of Acrylamide to the dissolved macromonomer solution. 3 minutes later the required amount of Span 20 (sorbitan monolaurate) was dissolved in the oil, which was st
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