Abstract

SO.09.07

Development of a hydrogel drug delivery system for local application on the retina

Karin Kobuch1, Mathias Maier1, Nikolaus Feucht1, A. Wolfstein2, D. Streufert2, L. Kroehne3, Chris P. Lohmann1
1Klinik und Poliklinik für Augenheilkunde, Klinikum rechts der Isar der Technischen Universität München, München; 2Acri.Tec GmbH, Carl Zeiss Meditec Company, Hennigsdorf; 3Capsulution NanoScience AG, Berlin

Objective
To develop a multifunctional “retina patch”, consisting of a hydrogel matrix with incorporated drugs for the treatment of retinal breaks and retinal diseases. The patch shall provide immediate closure of the break, prevention of cellular immigration and proliferation, and local extended-term drug delivery.
Methods
Different types of biopolymers (Alginates, Chitosan, hyaluronic acid) were tested in vitro on retinal cells and 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. Triamcinolonacetonid (TAAC) was chosen as the candidate drug to be released from the gel for clinical application. Different techniques for the incorporation of TAAC into the gel were established and evaluated with respect to homogenous distribution and delayed release of TAAC.
A surgical technique for implantation of the gel patch was developed in porcine eyes ex vivo.
Results
A biopolymer gel from crosslinked hyaluronic acid with a defined concentration of the crosslinker 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 very slow 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. A method for the incorporation of up to 12% of TAAC into the gel matrix could be established. A surgical technique for implantation of the gel patch was developed in porcine eyes ex vivo. In vivo implantations in rabbit eyes are under way.
Conclusions
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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