Contact lenses for pravastatin delivery to eye segments: Design and in vitro-in vivo correlations
| Autor: | Ana F. Pereira-da-Mota, Maria Vivero-Lopez, Maria Serramito, Luis Diaz-Gomez, Ana Paula Serro, Gonzalo Carracedo, Fernando Huete-Toral, Angel Concheiro, Carmen Alvarez-Lorenzo |
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| Přispěvatelé: | Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica, Universidade de Santiago de Compostela. Facultade de Farmacia |
| Rok vydání: | 2022 |
| Předmět: |
Drug-eluting contact lenses
Contact Lenses In vitro-in vivo correlations Pharmaceutical Science Hydrogels In vitro ocular release tests Cornea Drug Delivery Systems Animals Rabbits Hydroxymethylglutaryl-CoA Reductase Inhibitors Ophthalmic Solutions Ex vivo permeation studies Ocular biodistribution Pravastatin |
| Zdroj: | Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname Journal of Controlled Release |
| ISSN: | 1873-4995 |
| Popis: | Oral administration of cholesterol-lowering statins, HMG-CoA reductase inhibitors, is associated with beneficial effects on eye conditions. This work aims to design contact lenses (CLs) that can sustainedly deliver pravastatin and thus improve the ocular efficacy while avoiding systemic side effects of statins. Bioinspired hydrogels were prepared with monomers that resemble hydrophobic (ethylene glycol phenyl ether methacrylate) and amino (2-aminoethyl methacrylamide hydrochloride) functionalities of the active site of HMG-CoA. Best performing CLs loaded >6 mg/g, in vitro fulfilled the release demands for daily wearing, and showed anti-inflammatory activity (lowering TNF-α). High hydrostatic pressure sterilization preserved the stability of both the drug and the hydrogel network. Ex vivo tests revealed the ability of pravastatin to accumulate in cornea and sclera and to penetrate through transscleral route. In vivo tests (rabbits) confirmed that, compared to eye drops and for the same dose, CLs provided significantly higher pravastatin levels in tear fluid within 1 to 7 h of wearing. Moreover, after 8 h wearing pravastatin was present in cornea, sclera, aqueous humour and vitreous humour. Strong correlations between percentages of drug released in vitro and in vivo were found. Effects of volume and proteins on release rate and Levy plots were identified This project was funded by the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions grant agreement N° 813440 (ORBITAL–Ocular Research by Integrated Training And Learning). The work was also partially supported by MCIN [PID 2020-113881RB-I00/AEI/10.13039/501100011033], Spain, Xunta de Galicia [ED431C 2020/17], FEDER and by Fundação para a Ciência e a Tecnologia (FCT, Portugal) [UIDB/00100/2020 and PTDC/CTM-CTM/2353/2021]. M. Vivero-Lopez acknowledges Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) for a predoctoral research fellowship [ED481A-2019/120] SI |
| Databáze: | OpenAIRE |
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