DEVELOPMENT AND CHARACTERISATION OF PHOTOCROSSLINKABLE POLY(ETHYLENE CARBONATE) ELASTOMERS FOR LOCAL PROTEIN DELIVERY
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Therapeutic angiogenesis is a promising application of local protein delivery. Poly(ethylene carbonate) (PEC) is an interesting polymer due to its special degradation mechanism and good immunocompatibility and cytocompatibility. Its biggest advantage over commonly used aliphatic polyesters is that it does not degrade to acidic products implicated in protein denaturation and tissue inflammation. The degradation mechanism of linear PEC is thought to be oxidative, however the in vivo degradation rate is inappropriately rapid for angiogenic growth factor delivery. To reduce the PEC degradation rate, low molecular weight PEC diacrylates were formed and then UV photocrosslinked to form elastomers. The aims of this thesis were to evaluate the degradation and biocompatibility of these elastomers, and to determine formulation parameters that control the release of a model protein, bovine serum albumin, from porous elastomer matrices. Diacrylated prepolymers were successfully prepared with molecular weights from 2,000 Da to 12,000 Da. Elastomers were prepared from these prepolymers and characterised using NMR, DSC, ATR-FTIR, sol content and tensile testing. As hypothesized, crosslinking PEC slowed its degradation rate signifficantly compared to 60 kDa linear PEC (37 ± 4% mass loss in 12 weeks as compared to 78 ± 11% in 3 weeks). This result suggested that PEC degradation properties can be tuned for a range of tissue engineering or drug delivery applications. For both linear and elastomeric PEC, a typical foreign body reaction was observed. The degradation mechanism observed for the elastomer was the same as that for linear PEC and was consistent with the literature: cell-mediated surface erosion, which is demonstrated by linear mass loss, SEM observations, and pitted surface features. The in vitro release of BSA-loaded porous formulations was rapid and/or incomplete. The most promising formulation (12% BSA) produced a more prolonged release of two weeks than the other formulations tested, however the total fraction of BSA released was only 23%. The formulation parameter that most significantly affected the release of BSA was the amount of DMSO used to vortex BSA particles. These findings provide insight into the potential and limitations of PEC elastomers in protein delivery applications.