Hydrogel implants for transscleral diffusion delivery of topotecan: in vivo proof of concept in a rabbit eye model

0543808 - ÚMCH 2022 RIV GB eng J - Článek v odborném periodiku
Hobzová, Radka - Kodetova, M. - Pochop, P. - Uhlík, J. - Dunovska, K. - Svojgr, K. - Hraběta, J. - Feriancikova, B. - Cocarta, Ana-Irina - Širc, Jakub
Hydrogel implants for transscleral diffusion delivery of topotecan: in vivo proof of concept in a rabbit eye model.
International Journal of Pharmaceutics. Roč. 606, 5 September (2021), č. článku 120832. ISSN 0378-5173. E-ISSN 1873-3476
Grant CEP: GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) ED1.1.00/02.0109
Grant ostatní: AV ČR(CZ) StrategieAV21/10
Program: StrategieAV
Institucionální podpora: RVO:61389013
Klíčová slova: hydrogel * HEMA * topotecan
Obor OECD: Polymer science
Impakt faktor: 6.510, rok: 2021
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S0378517321006372?via%3Dihub

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.
Trvalý link: http://hdl.handle.net/11104/0321229