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AAPS PharmSciTech ; 25(5): 92, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684590

RESUMO

PURPOSE: Dry eye syndrome (DES), arising from various etiologic factors, leads to tear film instability and ocular surface damage. Given its anti-inflammatory effects, cyclosporine A (CsA) has been widely used as a short-term treatment option for DES. However, poor bioavailability and solubility of CsA in aqueous phase make the development of a cyclosporine A-based eye drop for ocular topical application a huge challenge. METHODS: In this study, a novel strategy for preparing cyclosporine A-loaded silk fibroin nanoemulsion gel (CsA NBGs) was proposed to address these barriers. Additionally, the rheological properties, ocular irritation potential, tear elimination kinetics, and pharmacodynamics based on a rabbit dry eye model were investigated for the prepared CsA NBGs. Furthermore, the transcorneal mechanism across the ocular barrier was also investigated. RESULTS: The pharmacodynamics and pharmacokinetics of CsA NBGs exhibited superior performance compared to cyclosporine eye drops, leading to a significant enhancement in the bioavailability of CsA NBGs. Furthermore, our investigation into the transcorneal mechanism of CsA NBGs revealed their ability to be absorbed by corneal epithelial cells via the paracellular pathway. CONCLUSION: The CsA NBG formulation exhibits promising potential for intraocular drug delivery, enabling safe, effective, and controlled administration of hydrophobic drugs into the eye. Moreover, it enhances drug retention within the ocular tissues and improves systemic bioavailability, thereby demonstrating significant clinical translational prospects.


Assuntos
Disponibilidade Biológica , Ciclosporina , Síndromes do Olho Seco , Fibroínas , Géis , Soluções Oftálmicas , Coelhos , Animais , Fibroínas/química , Ciclosporina/administração & dosagem , Ciclosporina/farmacocinética , Ciclosporina/química , Síndromes do Olho Seco/tratamento farmacológico , Soluções Oftálmicas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Administração Oftálmica , Solubilidade , Masculino , Emulsões/química , Córnea/metabolismo , Córnea/efeitos dos fármacos , Modelos Animais de Doenças
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