Chitosan-coated nanoemulsion for intranasal administration increases temozolomide mucosal permeation, cellular uptake, and In vitro cytotoxicity in glioblastoma multiforme cells

Autor(es)

Duarte, Jonatas Lobato ; Di Filippo, Leonardo Delello ; Vilella, Kelle Jarcy Azevedo ; Dutra, Jessyca Aparecida Paes ; Ribeiro, Diego Messalle ; da Silva, Monica Freitas ; de Medeiros, Alexandra Ivo ; Chorilli, Marlus

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 102, p. 10-pg., 2024-12-01.

Resumo

Glioblastoma multiforme (GBM) is the most prevalent and aggressive type of brain cancer in adults. Temozolomide (TMZ) is the chemotherapeutic agent used to treat primary central nervous system tumors. However, TMZ's clinical effectiveness faces several challenges due to its physical-chemical properties and biological features of GBM, such as the blood-brain barrier (BBB). Mucoadhesive nanosystems such as those coated with chitosan represent a promising alternative for optimizing the delivery of therapeutic agents to the central nervous system, as they possess ideal characteristics that enhance their interaction with the intranasal mucosa. We aimed to develop a chitosan-coated nanoemulsion containing temozolomide (CS-NE-TMZ) for nose-to-brain delivery and characterize its physical-chemical and in vitro biological properties. CS-NE-TMZ were obtained by emulsification followed by sonication. The optimized CS-NE-TMZ presented droplet size of 123,4 + 2,3 nm, polydispersity index of 0.273 + 0.028, zeta potential of +21,5 + 0,81 mV, entrapment efficiency of 100 + 1,91 % and drug loading of 2 + 0,007 %. An in vitro release study of CS-NE-TMZ showed sustained release for up to 24 h following the Korsmeyer-Peppas model with Fickian diffusion. CS-NE-TMZ demonstrated significantly enhanced ex vivo mucosal permeation, compared to free TMZ, and showed enhanced in vitro cellular uptake, selectively increasing cytotoxicity in U-87MG glioma cells but not in healthy L929 fibroblasts, reinforcing the potential of mucoadhesive nanoemulsions as effective intranasal drug delivery systems for future brain cancer therapies. (AU)

• 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: 20/12622-0 - Avaliação do potencial de carreadores lipídicos nanoestruturados funcionalizados com cetuximabe dispersos em hidrogéis termo-responsivos mucoadesivos para administração intranasal de temozolomida no tratamento do Glioblastoma Multiforme
• Beneficiário: Leonardo Delello Di Filippo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 22/11101-1 - Explorando o potencial de carreadores lipídicos nanoestruturados funcionalizados com cetuximabe dispersos em hidrogéis termo-responsivos mucoadesivos para a co-administração intranasal de temozolomida e acido elágico no tratamento do GBM
• Beneficiário: Jonatas Lobato Duarte
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 21/02609-9 - Avaliação do potencial de lipossomas funcionalizados com transferrina dispersos em hidrogéis mucoadesivos para administração nasal de temozolomida no tratamento do glioblastoma multiforme
• Beneficiário: Jessyca Aparecida Paes Dutra
• Modalidade de apoio: Bolsas no Brasil - Doutorado