Insights into the hydrolytic degradation of poly(1,3-glycerol carbonate)

Abstract

Event Abstract Back to Event Insights into the hydrolytic degradation of poly(1,3-glycerol carbonate) Fei Chen1, 2, Locke D. Huyer1 and Brian G. Amsden1, 2* 1 Queen's University, Department of Chemical Engineering, Canada 2 Queen's University, Human Mobility Research Centre, Canada Introduction: Aliphatic polycarbonates (APCs) are receiving increasing attention as biomaterials due to their biodegradability, non-toxicity and purported absence of acidic degradation products. Amongst these APCs, poly(1,3-glycerol carbonate) (PGC) has been intensively investigated because of the ease of functionalization of its pendant hydroxyl group. PGC reportedly degrades via hydrolysis[1], but no comprehensive study has been undertaken to ascertain its degradation mechanism. As its hydrolytic degradation mechanism and the nature of its degradation products have significant implications on its application, this study focused on determining these aspects in deionized water at pH 2, 7.4, 12 and within PBS buffer (pH 7.4). Materials and Methods: Poly(5-benzyloxy trimethylene carbonate) (PBTMC) and poly(trimethylene carbonate) (PTMC) were obtained by bulk ring-opening polymerization catalyzed by Sn(Oct)2 in the absence of initiator. PBTMC was debenzylated to yield PGC as described in Ray et al[2]. Mn and dispersity (ĐM) were measured by gel permeation chromatography with multi-angle laser light scattering. For in vitro degradation, 75 mg of PGC (~Mn 11800, ĐM 1.37) and PTMC (Mn 49550, ĐM 1.21) were placed in 1 mL glass vials of known weight. 1 mL of each pH stock solution was added to vials containing polymer (n = 3). The vials were placed in a shaker and maintained at 37°C. At sampling times, the solution was centrifuged, the supernatant decanted and the remaining product lyophilized and weighed to calculate the mass loss. The degradation products under pH 12 and PBS conditions were analyzed by electrospray mass spectrometry. Results and Discussion: PGC degraded rapidly under basic conditions; more than 90% mass loss was observed at pH 12 and in PBS (1x pH 7.4) after 1 day (Fig. 1A). In comparison, the mass loss of PGC at pH 2 and in un-buffered pH 7.4 required 3 weeks to reach a mass loss of 90%. At these pH conditions, mass loss was attributed to polymer dissolution as 11.8 kDa PGC is water-soluble (~15 mg/mL). No polymer backbone degradation was observed at pH 2 and only negligible degradation at pH 7.4 over the first 2 weeks (Fig. 1B), however the pH of the 7.4 media dropped to ~ 4. No degradation of PTMC occurred over 4 weeks in any of the media, indicating the importance of the pendant hydroxyl group for PGC hydrolysis. The observed degradation in PBS or alkaline medium was explained as a base-catalyzed intramolecular transesterification (Fig. 2)[3]. Nucleophilic attack of the pendant hydroxyl group on the adjacent carbonyl in the backbone leads to the formation of a stable five-membered ring intermediate. The oligomers further degrade into smaller non-toxic products[4]. The formation of the 5-membered ring product was confirmed by electrospray mass spectrometry, supporting the proposed degradation mechanism. Conclusion: This understanding of the degradation profile and mechanism of PGC should facilitate its use in biomedical applications. NSERC