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A. S. Fawcett, M. A. Brook; Photodimerization of Coumarin-Modified Silicones for Ophthalmic Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5316.
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Silicones are a key material for ophthalmic applications; they are widely used on the anterior of the eye in contact lenses, and in the posterior of the eye for vitreous humor substitutes, among many others. 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 a method for the attachment of small molecules to silicones that will allow for facile reversible crosslinking of siloxanes, which can control drug release, using light as a stimulus.
There are many ready available small molecules that can undergo dimerization with UV light. A small survey of these molecules was done that showed hydroxy-functionalized coumarin to be an excellent candidate. Coumarin is a natural product which will undergo a [2+2] photocycloaddition with UV light of > 300 nm and that can photocleave with < 280 nm. Coumarin-siloxane derivatives were synthesized via two methods: 1) photodimerization of coumarin, followed by hydrosilylation of hydride functional-silicones onto the dimerized coumarin and, 2) functionalization of coumarin with an activated alkyne followed by ‘click’ chemistry with azide functionalized silicones. These materials could then undergo UV induced crosslinking and photocleavage to create reversible photocrosslinked networks.
Coumarin-siloxane derivatives have successfully been prepared with various molecular weight silicones and a variety of reactive grafting site densities. These silicone networks can be crosslinked and photocleaved to create a reversible, but controlled, model drug release system. A study of release of selected drug surrogates was undertaken in order to understand the absorption and release profiles for these novel materials. Cytotoxicity studies with corneal epithelial cells and fibroblasts were performed along with swelling studies on these novel materials to determine their degree of utility for ophthalmic applications.
Coumarin functionalized silicones were prepared that can photodimerize to create a crosslinked network. This polymer network is an excellent candidate for controlled ophthalmic drug delivery due to its ability to reversibly cleave the crosslinked sites using light, which initiates spontaneous drug release.
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