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K. A. Kobuch, N. Feucht, A. Wolfstein, D. Streufert, L. Kroehne, M. Grabo, C. P. Lohmann; Development of a Hydrogel Drug Delivery System for Local Application on the Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4442.
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To develop a multifunctional "retina patch", consisting of a hydrogel matrix with an incorporated drug delivery system for the treatment of retinal breaks and local drug application in retinal diseases.
Different types of biopolymers (alginates, chitosan, hyaluronic acid) were tested in vitro on porcine retina in a perfusion tissue culture system with respect to biocompatibility, retinal adhesion and suitability for surgical implantation. Biodegradation of the gel in vitro was determined by the loss of weight after incubation with vitreous for up to 3 weeks or in BSS for up to 6 months. The homogenous incorporation of drugs into the gel matrix was tested with a model drug, a fluorescent nanoparticle based on Silizium. Triamcinolonacetonid (TAAC) was chosen as the candidate drug for clinical application. A surgical technique for implantation of the gel patch was developed in porcine eyes ex vivo.
A gel from hyaluronic acid in a 1mm thick layer showed excellent biocompatibility in retinal tissue culture, spontaneous retinal adhesion under air and BSS ex vivo in porcine eyes and suitable mechanical properties for an implantation technique with a special injector. There was no degradation of the amount of gel in vitro, when incubated in either vitreous samples or balanced salt solution. TAAC-containing micro- and nanoparticles could be manufactured. Delayed delivery of TAAC from these particles was demonstrated over a period of 16 days. Finally, a method for the incorporation of TA into the gel matrix was established and is actually further investigated. In vivo implantations in rabbit eyes are under way.
Basic steps for the development of a retina patch nanogel drug delivery system could be established and may show the feasibility of such a system for improved local treatment of retinal diseases.
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