Ex vivo model of human skin (hOSEC) for assessing the dermatokinetics of the anti-melanoma drug Dacarbazine

Autor(es)

Leite, Marcel Nani ^[1] ; Rosa Viegas, Juliana Santos ^[2] ; Garcia Praca, Fabiola Silva ^[2] ; de Paula, Natalia Aparecida ^[1] ; Zambelli Ramalho, Leandra Naira ^[3] ; Lopes Badra Bentley, Maria Vitoria ^[2] ; Cipriani Frade, Marco Andrey ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Div Dermatol, Wound Healing & Hansens Dis Lab, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol & Legal Med, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmaceutical Sciences; v. 160, MAY 1 2021.
• Citações Web of Science: 0

Resumo

Alternative models to replace animals in experimental studies remain a challenge in testing the effectiveness of dermatologic and cosmetic drugs. We proposed a model of human organotypic skin explant culture (hOSEC) to assess the profile of cutaneous drug skin distribution, adopting dacarbazine as a model, and respective new methodologies for dermatokinetic analysis. The viability tests were evaluated in primary keratinocytes and fi-broblasts, and skin by MTT and TTC assays, respectively. Then, dacarbazine was applied to the culture medium, and the hOSEC method was applied to verify the dynamics of skin distribution of dacarbazine and determine its dermatokinetic profile. The results of cell and tissue viability showed that both were considered viable. The dermatokinetic results indicated that dacarbazine can be absorbed through the skin, reaching a concentration of 36.36 ?g/mL (18,18%) of the initial dose (200 ?g/mL) after 12 h in culture. Histological data showed that the skin maintained its structure throughout the tested time that the hOSEC method was applied. No apoptotic cells were observed in the epidermal and dermal layers. No visible changes in the dermo-epidermal junction and no inflammatory processes with the recruitment of defense cells were observed. Hence, these findings suggest that the hOSEC concept as an alternative ex vivo model for assessing the dynamics of skin distribution of drugs, such as dacarbazine, and determining their respective dermatokinetic profiles. (AU)

• Processo FAPESP: 16/16437-7 - Avaliação da viabilidade do modelo de pele humana ex vivo (hOSEC) e sua aplicação em estudos de eficácia de protetores solares a longo prazo no fotoenvelhecimento
• Beneficiário: Marco Andrey Cipriani Frade
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/04448-2 - Desenvolvimento de carreador lipídico nanoestruturado contendo pool de siRNAs associados à agente antitumoral como uma abordagem terapêutica multifuncional para o Câncer de pele
• Beneficiário: Juliana dos Santos Rosa
• Modalidade de apoio: Bolsas no Brasil - Doutorado