Thermo-responsive and mucoadhesive gels for the treatment of cystinosis

Mucoadhesive thermogels were developed by crosslinking poly(n-isopropylacrylamide) based polymers with chitosan and incorporating disulfide bridges, capable of releasing cysteamine upon interaction with mucin, for the treatment of cystinosis. Through crosslinking with chitosan and incorporating varying concentrations of the disulfide monomer into the polymer backbone, the extent of how mucoadhesive the developed thermogels were could be controlled. Through disulfide bridging with mucin, the thermogels released 6 to 10 & mu;g of the conjugate model 2-mercaptopyridine over five days. Utilizing chitosan as the crosslinker, the developed thermogels were shown to degrade to a statistically higher extent following incubation with lysozyme, the highest concentration tear enzyme, by gravimetric and rheologic analysis. The developed thermogels were extensively tested in vivo utilizing a rat model in which materials were applied directly to the corneal surface and a rabbit model in which thermogels were applied to the inferior fornix. With the developed models, there was no adverse reactions or visual discomfort incurred following application of the thermogels. It has been demonstrated that the thermogels produced can be applied to the inferior fornix and release the stable conjugated payload over several days. The developed thermogel was designed to improve upon the current clinical treatment options for ocular cystinosis which are acidic topical formulations that require reapplication multiple times a day.