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Thermoresponsive Hydrogel Containing Viscum album Extract for Topic and Transdermal Use: Development, Stability and Cytotoxicity Activity

2021; Multidisciplinary Digital Publishing Institute; Volume: 14; Issue: 1 Linguagem: Inglês

10.3390/pharmaceutics14010037

1999-4923

João Vitor da Costa Batista, Ana Paula dos Santos Matos, Adriana P. Oliveria, Eduardo Ricci‐Júnior, Zaida Maria Faria de Freitas, Catarina Amorim Oliveira, Helena Keiko Toma, Márcia Alves Marques Capella, Leandro Rocha, Ulrike Weissenstein, Stephan Baumgartner, Carla Holandino,

Plant and animal studies

Viscum album L. (Santalaceae), also known as European mistletoe, is a semi-parasitic plant that grows on different host trees. Our group recently demonstrated the antitumoral activity of ethanolic V. album extracts in vitro, depending on the dose and the host tree, V. album ssp abietis from Abies alba being the most active extract. The goal of this work focused on the development of a new topical formulation containing V. album extracts, evaluation of in vitro toxicity and ex vivo skin permeation assays. The Poloxamer 407 hydrogel containing 5% of dry (VA_DEH) or aqueous (VA_AEH) extract presented dermal compatible pH and microbiological stability for 180 days. The hydrogels flow curve presented a non-linear relation, characteristic of non-Newtonian fluids, and the mean viscosity for the VA_DEH and VA_AEH was 372.5 ± 7.78 and 331.0 ± 2.83 Pa.s, respectively, being statistically different (Welch's t test; p < 0.01). Additionally, WST-1 in vitro assays revealed a dose-dependent toxicity for both formulations and VA_DEH presented a higher activity than the VA_AEH. The promising cytotoxic potential of VA_DEH lead to the ex vivo skin permeation assay with 2.73 ± 0.19 µg/cm2 of chlorogenic acid, which permeated at 8 h, showing a transdermal potential. These in vitro results support the idea that VA_DEH is a novel promising candidate for mistletoe therapy. Therefore, further in vivo and pre-clinical experiments should be performed to evaluate the safety and efficacy of this new dermic delivery system.