Toxicological Assessment of 2-Hydroxychalcone-Mediated Photodynamic Therapy: Comparative In Vitro and In Vivo Approaches

Autor(es)

Bila, Niura Madalena ; Vaso, Carolina Orlando ; Belizario, Jenyffie Araujo ; Assis, Leticia Ribeiro ; Regasini, Luis Octavio ; Fontana, Carla Raquel ; Fusco-Almeida, Ana Marisa ; Costa-Orlandi, Caroline Barcelos ; Mendes-Giannini, Maria Jose Soares

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICS; v. 16, n. 12, p. 14-pg., 2024-12-01.

Resumo

Background: Photodynamic therapy (PDT) is a treatment modality that uses light to activate a photosensitizing agent, destroying target cells. The growing awareness of the necessity to reduce or eliminate the use of mammals in research has prompted the search for safer toxicity testing models aligned with the new global guidelines and compliant with the relevant regulations. Objective: The objective of this study was to assess the impact of PDT on alternative models to mammals, including in vitro three-dimensional (3D) cultures and in vivo, in invertebrate animals, utilizing a potent photosensitizer, 2-hydroxychalcone. Methods: Cytotoxicity was assessed in two cellular models: monolayer (2D) and 3D. For this purpose, spheroids of two cell lines, primary dermal fibroblasts (HDFa) and adult human epidermal cell keratinocytes (HaCat), were developed and characterized following criteria on cell viability, shape, diameter, and number of cells. The survival percentages of Caenorhabditis elegans and Galleria mellonella were evaluated at 1 and 7 days, respectively. Results: The findings indicated that all the assessed platforms are appropriate for investigating PDT toxicity. Furthermore, 2-hydroxychalcone demonstrated low toxicity in the absence of light and when mediated by PDT across a range of in vitro (2D and 3D cultures) and in vivo (invertebrate animal models, including G. mellonella and C. elegans) models. Conclusion: There was a strong correlation between the in vitro and in vivo tests, with similar toxicity results, particularly in the 3D models and C. elegans, where the concentration for 50% viability was approximately 100 mu g/mL. (AU)

• Processo FAPESP: 20/15586-4 - Estabelecimento de um modelo tridimensional para determinação da eficácia e segurança farmacológica de derivados de nitrofuranos e indólicos e avaliação da infecção de Histoplasma capsulatum
• Beneficiário: Carolina Orlando Vaso
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
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• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 18/02785-9 - Dermatófitos e Dermatofitoses: formação de biofilme e desenvolvimento de estratégias de controle.
• Beneficiário: Maria José Soares Mendes Giannini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/18388-6 - O papel do biofilme na patogênese das dermatofitoses e desenvolvimento de estratégias de combate
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• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
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• Beneficiário: Maria José Soares Mendes Giannini
• Modalidade de apoio: Auxílio à Pesquisa - Regular