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L. A. Wells, H. Sheardown; Photoresponsive Hyaluronic Acid for Ophthalmic Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5163.
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Photoresponsive hyaluronic acid has 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. Sustained release devices have significant therapeutic advantages for treating diseases of back of the eye by increasing patient compliance and maintaining therapeutic levels of the drug. Intravitreal sustained-release delivery systems that respond to light stimuli are under development to control the rate of delivery resulting in a tuneable treatment profile ideal for macular degeneration and diabetic retinopathy therapies.
Hyaluronic acid (HA) photoresponsive hydrogels were synthesized using anthracene-based photocrosslinker technology that has previously been applied successfully to alginate. Anthracene-based crosslinkers were chemically grafted to HA polymer backbones and light irradiation above and below 300 nm effectively caused HA crosslinking and decrosslinking. Loading and release of Coomassie Brilliant blue (CB) from the gels into PBS was used to assess the ability for the system to have altered release profiles in response to light stimuli.
When grafted to HA the anthracene-based photoresponsive crosslinkers formed hydrogels that demonstrated low cytotoxicity properties with ophthalmic cell lines. In addition to UV induced crosslinking, light irradiation can further control the swelling and drug delivery properties from photocrosslinked HA as illustrated through the decrease or increase in delivery of the model drug CB after specified UV light treatments. Minimally light treated HA photogels had complete delivery of CB and gel dissolution by 700 hours whereas irradiation with 365nm light increased delivery times resulting in 32% of CB released at 2000 hours. The incorporation of photosensitive anthracene capped star-polyethylene glycol further increased the photoresponsiveness of the gels.
The anthracene-based photoresponsive crosslinker can act to control HA crosslinking and drug delivery via a light irradiation mechanism. Its end group versatility opens possibilities to graft similar photosensitive crosslinkers to a variety of hydrogels.
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