Design of polymer systems and surface-active agents for the improvement of cell attachment for treatment of ocular diseases

Abstract

The degradation of eyesight is a frightening experience for individuals and unfortunately gradual loss of vision with old age is commonplace. One of the most common forms of eye disease which effects vision is Age-Related Macular Degeneration (AMD). AMD is the leading cause of blindness in the developed world and there is currently no cure for the disease. One treatment option available for the neovascular form of AMD is the injection of Bevacizumab [an anti-vascular endothelial growth factor (VEGF) drug] into the eye on a monthly basis.
Investigation into the biodegradable polymers poly(L-lactic acid) (PLLA) and poly(D,L-lactic-co-glycolic acid) (PLGA) as a possible drug delivery system with highly uniform and reproducible microspheres was developed. Under optimised parameters Bevacizumab-encapsulated PLLA:PLGA microspheres were successfully prepared with a steady release of Bevacizumab being obtained.
Additionally, fibrous scaffolds of methyl methacrylate (MMA) and poly(ethylene glycol) methacrylate (PEGM) were prepared by an electrospinning process. These MMA:PEGM co-polymers were investigated as a possible Bruchs membrane replacement and as the support for retinal pigment epithelium (RPE) transplantation. The MMA:PEGM co-polymers were functionalised with N-succinimidyl which resulted in the fibres forming a gel in vitro. Gel formation was examined further and successful RPE cell attachment and growth onto these gels was observed. Further work on surface active agents was undertaken to improve the cell adhesion, proliferation and growth of RPE cells onto these methacrylate based frameworks. An arginine-glycine-aspartic acid (RGD) peptidomimetic was prepared and reacted onto the surface of the MMA:PEGM co-polymers, however, the peptidomimetic-attached MMA:PEGM fibres offered little improvement in cell growth in comparison with N-succinimidyl–activated MMA:PEGM co-polymer fibres.
Additional attachment of the natural proteins laminin, collagen and fibronectin onto the microspheres was achieved. Attachment of these proteins prolonged the release of the dye from the microspheres and showed no cytotoxic effects when examined in-vitro.

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ORCID for Martin C. Grossel: orcid.org/0000-0001-7469-6854

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