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Ben B. Muirhead, Heather Sheardown, Michael A. Brook, Scott D. Fitzpatrick; The Biological Feasibility Of Various Novel Poly(n-isopropylacrylamide) Formulations As A Delivery Vehicle To The Posterior Of The Eye. Invest. Ophthalmol. Vis. Sci. 2011;52(14):470.
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The back of the eye is notoriously difficult to treat, often requiring complex and invasive surgical intervention. While cell based therapies have shown promise, traditionally the cells are delivered via bolus liquid suspension, or as a cell sheet grown ex vivo. PNIPAAm, a thermoresponsive intelligent material which undergoes a reversible transition from liquid to gel when heated above a lower critical solution temperature (LCST) of approximately 32C, combines the strengths of these modalities. However, the polymer is not degradable and does not contain cell adhesive residues. Therefore it is of interest to prepare materials which gel in situ but which possess additional desirable properties.
Novel formulations of PNIPAAm were prepared to include hydrophilic residues, cell adhesion peptides, and hydrolytically degradable groups. The biological feasibility of these materials for ocular applications was examined using a variety of in vitro and in vivo experiments. Materials were tested using histological sectioning of subcutaneous implantation sites on a murine model. Further, the liver and spleen of sacrificed animals were examined to verify systemic effects. Blood was also taken from these animals to observe the development of any humoral response. In vitro work included MTT cell viability assays using a retinal pigment epithelium cell line (RPE cells).
Novel materials were characterized using a variety of techniques. MTT viability assays showed no toxicity to RPE cells. H&E staining of explanted sections did not show any adverse reaction to implanted material in most cases over a period of more than 60 days. Liver and spleen sectioning showed material was not being phagocytised by immune cells, or affecting liver function with toxic breakdown products. Ongoing drug release studies demonstrated the potential of these materials for drug delivery with functionalization resulting in improved drug release kinetics.
Novel poly(NIPAAM) based polymers with the ability to gel in situ have been developed. This material creates a potentially intriguing cell and drug delivery system for the posterior section of the eye. Functionalization with N-acryloxysuccinimide allows for improved drug release kinetics. Biological characterization of these materials verifies their potential for use in vivo.
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