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W. F. Mieler, P. Drapala, S. Benac, E. M. Brey, V. Perez-Luna, J. J. Kang Derwent; Thermo-Responsive Hydrogel Drug Delivery System for the Posterior Segment of the Eye. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3873.
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© ARVO (1962-2015); The Authors (2016-present)
The main objective is to characaterize thermo-responsive hydrogels as a novel posterior segment drug delivery platform in the treatment of age-related macular degeneration (AMD) and other posterior segment vascular diseases.
Hydrogels were synthesized using poly(N-isopropylacrylamide) (PNIPAAm) and crosslinked with poly(ethylene glycol) diacrylate (PEG-DA). Bovine Serum Albumin (BSA) and Immunoglobulin G (IgG) were encapsulated into the hydrogels and the release profiles of these proteins at various timepoints were analyzed via a Badford assay. Avastin was also subsequently studied.
The crosslinked PNIPAAm hydrogels exist as a solution at room temperature, though upon exposure to body temperature, rapidly convert into a gel and encapsulate the protein. Rheological studies showed that as PEG-DA concentration increased, both the viscous and elastic modulus properties also increased. As the crosslinker density varied, the rate of protein release was also affected. Less densely crosslinked hydrogels showed faster protein release, and were more readily injectible into a rodent eye via a 27 gauge needle. Release prolifes of BSA and IgG showed an initial burst of protien release (average 40%) within 24 hours, and then reached a steady state of sustained release for up to three weeks. Upon examination of the gels after the release experiment, approximately 35% of the protein remained entrapped in the hydrogel. Studies with Avastin showed successful encapsulation and release. Post-release viability studies are ongoing. Cell washings show no evidence of toxicity in in vitro endothelial cell studies.
Thermo-responsive hydrogels were successfully synthesized and exhibited fast and reversible phase changes. The gels were able to successfully encapsulate and release protein, including Avastin. The current hydrogel formulation will be modified to extend the release time beyond the currently studied three week timeframe, and the crosslinkers will be modified to become fully biodegradable. Thermo-responsive hydrogels appear to a promising new posterior segment drug delivery platform for agents employed in the treatment of AMD and other posterior segment vascular diseases. CR: None. Support: The Lincy Foundation.
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