Nanostructured lipid carriers loaded into in situ gels for breast cancer local treatment

Autor(es)

Passos, Julia S. ; Apolinario, Alexsandra C. ; Ishida, Kelly ; Martins, Tereza S. ; Lopes, Luciana B.

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmaceutical Sciences; v. 192, p. 18-pg., 2023-11-23.

Resumo

In this study, nanostructured lipid carriers (NLC) were developed and employed to obtain in situ thermosensitive formulations for the ductal administration and prolonged retention of drugs as a new strategy for breast cancer local treatment. NLC size was influenced by the type and concentration of the oil phase, surfactants, and drug incorporation, ranging from 221.6 to 467.5 nm. The type of liquid lipid influenced paclitaxel and 5-fluorouracil cytotoxicity, with tributyrin-containing NLC reducing IC50 values by 2.0-7.0-fold compared to tricaprylin NLC in MCF-7, T-47D and MDA-MB-231 cells. In spheroids, the NLCs reduced IC50 compared to either drug solution (3.2-6.2-fold). Although a significant reduction (1.26 points, p < 0.001) on the health index of Galleria mellonella larvae was observed 5 days after NLC administration, survival was not significantly reduced. To produce thermosensitive gels, the NLCs were incorporated in a poloxamer (11 %, w/w) dispersion, which gained viscosity (2fold) at 37degree celsius. After 24 h, similar to 53 % of paclitaxel and 83 % of 5-fluorouracil were released from the NLC; incorporation in the poloxamer gel further prolonged release. Intraductal administration of NLC-loaded gel increased the permanence of hydrophilic (2.2-3.0-fold) and lipophilic (2.1-2.3-fold) fluorescent markers in the mammary tissue compared to the NLC (as dispersion) and the markers solutions. In conclusion, these results contribute to improving our understanding of nanocarrier design with increased cytotoxicity and prolonged retention for the intraductal route. Tributyrin incorporation increased the cytotoxicity of paclitaxel and 5-fluorouracil in monolayer and spheroids, while NLC incorporation in thermosensitive gels prolonged tissue retention of both hydrophilic and hydrophobic compounds. (AU)

• 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: 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: 20/01208-8 - Sistemas nanoestruturados bioadesivos para administração intraductal e tratamento localizado do Câncer de Mama
• Beneficiário: Julia Sapienza Passos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• 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