Hydrogel implants for transscleral diffusion delivery of topotecan: In vivo proof of concept in a rabbit eye model
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
34175379
DOI
10.1016/j.ijpharm.2021.120832
PII: S0378-5173(21)00637-2
Knihovny.cz E-zdroje
- Klíčová slova
- HEMA, Hydrogel, Intraocular delivery, Retinoblastoma, Topotecan, Transscleral diffusion,
- MeSH
- hydrogely MeSH
- králíci MeSH
- nádory sítnice * MeSH
- retinoblastom * MeSH
- sklivec MeSH
- topotekan MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- hydrogely MeSH
- topotekan MeSH
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.
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