Monoolein-based nanodispersions for cutaneous co-delivery of methylene blue and metformin: Thermal and structural characterization and effects on the cutaneous barrier, skin penetration and cytotoxicity

Autor(es)

Donadon, Larissa Gabriella Fusco ; Salata, Giovanna Cassone ; Goncalves, Thalita Pedralino ; Matos, Lisa de Carvalho ; Evangelista, Maria Clara Paiva ; da Silva, Nicole Sampaio ; Martins, Tereza Silva ; Machado-Neto, Joao Agostinho ; Lopes, Luciana Biagini ; Garcia, Maria Teresa Junqueira

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Pharmaceutics; v. 633, p. 18-pg., 2023-02-01.

Resumo

This study evaluated the potential of monoolein (MO)-based nanodispersions to promote the cutaneous co -delivery of metformin (MET) and methylene blue (MB) for the treatment of non-melanoma skin cancer. MO -based nanodispersions were obtained using Kolliphor (R) P407 (KP) and/or sodium cholate (CH), and character-ized concerning the structure, thermal stability, ability to disrupt the skin barrier, cutaneous permeation and retention of MB and MET. Additionally, the cytotoxic effect of MO nanodispersions-mediated combination therapy using MET and MB in A431 cells was evaluated. The nanodispersions exhibited nanometric size (<200 nm) and thermal and physical stability. Small angle X-ray scattering studies revealed multiple structures depending on composition. They were able to interact with stratum corneum lipid structure, increasing its fluidity. The effect of MO-nanodispersions on topical/transdermal delivery of MB and MET was composition -dependent. Nanodispersions with low MO content (5 %) and stabilized with KP and CH (0.05-0.10 %) were the most promising, enhancing the cutaneous delivery of MB and MET by 1.9 to 2.2-fold and 1.4 to 1.7-fold, respectively, compared to control. Cytotoxic studies revealed that the most promising MO nanodispersion-mediated combination therapy using MET and MB (1:1) reduced the IC50 by 24-fold, compared to MB solu-tion, and a further reduction (1.5-fold) was observed by MB photoactivation. (AU)

• Processo FAPESP: 17/18239-0 - Nanoemulsões como sistemas de liberação do azul de metileno e da metformina para tratamento do câncer de pele: estudos de liberação, permeação/retenção 'in vitro' e citotoxicidade.
• Beneficiário: Maria Teresa Junqueira Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/13877-1 - Nanocarreadores para a quimioprevenção e tratamento localizado de tumores de mama
• Beneficiário: Luciana Biagini Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 17/17844-8 - Sílica nanoestruturada como veículo protetor de vacinas e biomoléculas
• Beneficiário: Osvaldo Augusto Brazil Esteves Sant'Anna
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/08582-5 - EMU concedido no processo 17/17844-8:Analisador térmico - TG/DTA modelo sta 2500 TG/DTA TEMP. ambiente a 1100 °c
• Beneficiário: Tereza da Silva Martins
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 19/26048-6 - Desenvolvimento e aplicação de nanocarreadores multifuncionais para entrega intraductal de quimioterápicos visando o tratamento do Câncer de Mama
• Beneficiário: Giovanna Cassone Salata
• Modalidade de apoio: Bolsas no Brasil - Doutorado