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Impact of Storage on In Vitro Permeation and Mucoadhesion Setup Experiments Using Swine Nasal Mucosa

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Autor(es):
de Araujo, Jaiza Samara Macena ; Augusto, Gabriela Gama Xavier ; Pestana, Aylla Mesquita ; Groppo, Francisco Carlos ; Rodrigues, Flavia Sammartino Mariano ; Novaes, Pedro Duarte ; Franz-Montan, Michelle
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: AAPS PHARMSCITECH; v. 26, n. 1, p. 13-pg., 2024-12-05.
Resumo

Intranasal topical administration offers a promising route for local and systemic drug delivery, with in vitro permeation and mucoadhesion studies often using porcine models. However, the impact of storage on mucosal integrity after the procedure remains unaddressed. This study aimed to standardize the preparation process and evaluated whether storage of porcine nasal mucosa impairs its integrity and permeability for experimental comparisons. Additionally, an optimized in vitro mucoadhesion experiment using texture analyzer equipment was investigated. Porcine nasal mucosa was subjected to different storage conditions ("fresh"; refrigerated at 4 degrees C for 24 h and 48 h, and frozen at -20 degrees C for two or three weeks) and assessed using optical and transmission electron microscopy. In vitro permeation assays were performed in a Franz-type vertical diffusion system with lidocaine hydrochloride (LDC). In vitro mucoadhesion assays were conducted using fresh nasal mucosa and a commercial nasal topical formulation using TA.XT. Plus texture analyzer. The variables involved (probe speed, contact time, and application force) in assessing mucoadhesive capacity (maximum mucoadhesive force F-max and work of mucoadhesion W-muc) were optimized using a Central Composite Design. Fresh tissues showed no alterations in histological arrangement or in the ultrastructure of adherence junctions. Stored tissues exhibited histological disorganization, reduced thickness, and loss of epithelial integrity. LDC permeability increased in storage tissues (p < 0.05). Contact force had a positive effect on F-max and W-muc (p < 0.0001), with a minimum required value of 0.48 N. Variations in contact time and probe speed did not affect the responses (p > 0.05). In conclusion, the preparation technique was adequate to maintain mucosa integrity for permeability studies. However, storing the mucosa at 4 or -20 degrees C overestimated LDC permeation, which could mislead critical data for formulation development. Therefore, the use of fresh mucosa is recommended to ensure more reliable results. For in vitro mucoadhesion assays, a minimum contact force of 0.48N is required for optimal responses. (AU)

Processo FAPESP: 14/14457-5 - Carreadores baseados em lipídios (SLN/NLC e lipossomas com gradiente iônico) como estratégia para aumentar a encapsulação e a potência de anestésicos locais
Beneficiário:Eneida de Paula
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 19/05692-4 - Avaliação das mucosas nasal e sublingual suínas como barreiras biológicas para ensaios de permeação in vitro: análise histológica e de resistividade elétrica
Beneficiário:Gabriela Gama Xavier Augusto
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 20/03786-9 - Sistemas de liberação para anestesia tópica em odontologia: avaliação in vitro e in vivo
Beneficiário:Michelle Franz Montan Braga Leite
Modalidade de apoio: Auxílio à Pesquisa - Regular