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L. A. Wells, H. Sheardown; Photoreversible Alginate for Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5817.
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Photoresponsive polymers have the potential to act as controllable drug delivery systems and may be particularly suited for disease treatment in the posterior segment of the eye. Sustained release devices have significant therapeutic advantages for treating diseases of the relatively inaccessible back of the eye by increasing patient compliance and maintaining therapeutic levels of the drug in the ocular tissue for months or years further increasing its effectiveness. Intravitreal sustained-release delivery systems that respond to light stimuli are under development to control the rate of delivery in response to disease progression or regression resulting in a tuneable treatment profile ideal for macular degeneration and diabetic retinopathy therapies.
Alginate, an intravitreally-inert polymer that has shown promise as an ophthalmic drug delivery vehicle, will be covalently crosslinked by photosensitive molecules. Anthracene can be grafted to alginate via PEG chains. Photoreversible anthracene is on one side to give chains the ability to photodimerize and an amine group is on the other side of the PEG chain so it can be bound to the carboxylic acid groups of alginate using carbodiimide chemistry. Ultimately two specific wavelengths of UV light will be used to crosslink and decrosslink alginate to provide adjustable drug delivery profiles.
Preliminary studies have shown significant release times of small amounts of proteins from physically crosslinked alginate microspheres for over 8 months. Initial bifunctional photoswitchable anthracene-terminated PEG chains have been developed and synthesized using protecting group and carbodiimide-based chemistry. Preliminary studies have demonstrated successful synthesis through NMR and UV/vis spectrophotometry. These gels show the potential for UV induced crosslinking. Addition of the alginate is expected to lead to improved gel properties.
A photocrosslinkable PEG-anthracene molecule has been synthesized and shown to form weak gels under appropriate UV conditions. These gels are expected to reversibly crosslink alginate. The photoreversible properties of the resultant gels will be examined spectrophotometrically after UV light treatments and will be tailored to provide reversibly tuneable controlled release.
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