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Amanda Fawcett, Scott D Fitzpatrick, Heather Sheardown; Thermogelling PNIPAAm-Based Materials as an in situ-Forming Drug Delivery Device. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5271.
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Drug delivery to the posterior segment of the eye has proven to be extremely problematic both with respect to efficacious delivery profile and patient compliance. The focus of this project is to develop novel thermogelling materials that are both injectable and degradable after extended period of drug delivery. In this work, novel covalently crosslinked pNIPAAm-based materials will be compared to past work involving non-crosslinked materials for efficacy as an injectable-in situ gelling device.
Poly(N-isopropylacrylamide) has an LCST around physiological temperatures, and therefore can form gels when heated to 37 °C. Transparent degradable gels were previously prepared using pNIPAAm, however, the low mechanical strength can impede the ability of the materials to provide extended release. Materials were synthesized via radical-initiated polymerization of pNIPAAm, NAS (Acrylic acid N-hydroxysuccinimide ester), DBA (Acryloyloxy-β,β-dimethyl-γ-butyrolactone), and/or PLA with PEG as a crosslinker. The transparency of the gels was assessed, and the Young’s modulus was determined by Instron testing.
These novel materials exhibit rapid gelation; with the degree of transparency and mechanical strength, showing a correlation with the gel concentration. The incorporation of an internal crosslinker was found to increase the overall mechanical strength of the gels. A library of unique materials and a review of their properties will be discussed.
While these materials require continued optimization, these results suggest that injectable polymers comprised of pNIPAAm, PEG and/or PLA may have the potential for use in ophthalmic drug delivery applications.
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