Dynamic ex vivo porcine eye model to measure ophthalmic drug penetration under simulated lacrimal flow

• Autor(a) principal: Barbalho, Geisa Nascimento
• Data de Publicação: 2023
• Outros Autores: Falcão, Manuel Alves, Lopes, Jefferson Márcio Sanches, Lopes, Júlia M., Contarato, Jonad Logan Adriano, Gelfuso, Guilherme Martins, Cunha Filho, Marcílio Sérgio Soares da, Gratieri, Taís
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UnB
• Texto Completo: http://repositorio2.unb.br/jspui/handle/10482/48033; https://doi.org/10.3390/pharmaceutics15092325; https://orcid.org/0000-0002-3092-0137; https://orcid.org/0000-0002-1924-7885; https://orcid.org/0000-0002-9167-6852; https://orcid.org/0000-0001-6481-2364
• topic: Medicamentos - administração; Oftalmologia; Modelo animal

Animal models are still used in the research and development of ophthalmic drug products, mainly due to the difficulty in simulating natural physiological conditions with in vitro models, as there is a lack of dynamic protection mechanisms. Therefore, developing alternative ophthalmic models that evaluate drug penetration in the cornea while applying dynamic protection barriers is a contemporary challenge. This study aimed to develop a dynamic ex vivo model using porcine eyes with a simulated lacrimal flow to evaluate the performance of pharmaceutical drug products. A glass donor cell to support a simulated tear flow was designed, optimized, and custom-made. The system was challenged with different formulations (with fluconazole) including excipients with different viscosities (poloxamer 407) and mucoadhesive properties (chitosan). The results were compared to those obtained from a conventional excised cornea model mounted in Franz-type diffusion cells. The dynamic model could differentiate formulations, while the static model did not, overestimating ex vivo drug penetrated amounts. Hence, the dynamic model with simulated tear flow showed to be a simple and promising new alternative method for the drug penetration of ophthalmic formulations that ultimately can reduce the number of animals used in research.