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L. A. Wells, H. Sheardown; Protein Delivery and in vitro Testing of Photoresponsive Hydrogels. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5310.
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Photoresponsive hydrogels have the potential to act as a controllable drug delivery system and may be particularly suited for disease treatment in the posterior segment of the eye due to accessibility of the tissue to light. Intravitreal sustained-release delivery systems that respond to light stimuli are under development to control the rate of delivery of large molecules.
Hyaluronic acid (HA) photoresponsive hydrogels (photogels) were synthesized using anthracene-based photocrosslinker technology. Anthracene-based crosslinkers were chemically grafted to HA polymer backbones and light irradiation above and below 300 nm effectively caused HA crosslinking and decrosslinking. In vitro testing was performed to determine enzymatic degradation rates and the cytocompatibility of the crosslinker, gels and gel degradation products with ophthalmic cell lines. Release studies investigated the influence of UV light with the delivery of high molecular weight proteins into PBS with laser and light treatments.
Photogel degradation rates were significantly increased after UV crosslinking treatments from 200 hours to over 3000 hours in PBS and from 48 hours to over 440 hours in 100 Units/mL of hyaluronidase. Using the MTT assay, there were no significant differences in cell viability with retinal pigment epithelial cells grown in indirect contact with photogels or with photogel degradation products versus controls. Diffusion properties from the photogels were measured from release rates of model compounds from the photogels after specified UV treatments. For example, delivery times of Coomassie blue could be increased from 700 hours to over 2000 hours with 365 nm light treatments. Furthermore, UV treatments of 365 nm could "turn off" protein release from the photogels which could subsequently be "turned back on" with 248 nm laser treatments.
PEG-anthracene can act to control HA crosslinking, degradation, and drug delivery in response to UV exposure. The resulting photogels have demonstrated cytocompatibility and show the potential to both incrementally control drug release and turn release off and on via UV light and lasers.
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