Treatment of retinoblastoma (Rb) has greatly improved in recent years in terms of survival and eye salvage rates, using mainly intra-arterial or intravitreal chemotherapy. However, the treatment of vitreous tumor seeding still represents a challenge and it is of great interest to develop new strategies to deliver pharmacologically sufficient drug amounts to the vitreous humor. In the present work, we present a lens-shaped bi-layered hydrogel implant for delivery of topotecan (TPT) via transscleral diffusion. The implant consists of an inner TPT-loaded poly(2-hydroxyethyl methacrylate) (pHEMA) layer adjacent to the sclera and an outer covering poly(2-ethoxyethyl methacrylate) (pEOEMA) layer impermeable to TPT. TPT-loaded pHEMA samples exhibit long-lasting in vitro cytotoxicity against the Rb cell line Y79. In an in vivo experiment, pHEMA/pEOEMA implants are successfully surgically administered to the posterior segment of rabbit eyes. The determination of TPT pharmacokinetics demonstrates the attainment of promising levels of TPT (10 ng/ml) in vitreous humor 8 h after implant placement. The results from the pilot experiment constitute the proof of principle for the use of the proposed implants as a drug delivery system for the local treatment of intraocular diseases.

Department of Histology and Embryology 2 Faculty of Medicine Charles University 5 Uvalu 84 150 06 Prague 5 Czech Republic

Department of Medical Chemistry and Clinical Biochemistry Charles University 2 Faculty of Medicine and University Hospital Motol 5 Uvalu 84 150 06 Prague 5 Czech Republic

Department of Ophthalmology 2 Faculty of Medicine Charles University and Motol University Hospital 5 Uvalu 84 150 06 Prague 5 Czech Republic

Department of Pediatric Hematology and Oncology 2 Faculty of Medicine Charles University and Motol University Hospital 5 Uvalu 84 150 06 Prague 5 Czech Republic

Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic Heyrovsky Sq 2 162 06 Prague 6 Czech Republic

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