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In vitro Development of Controlled-Release Nanoniosomes for Improved Delivery and Anticancer Activity of Letrozole for Breast Cancer Treatment

INTRODUCTION: Breast cancer is among the most prevalent mortal cancers in women worldwide. In the present study, an optimum formulation of letrozole, letrozole-loaded niosome, and empty niosome was developed, and the anticancer effect was assessed in in vitro MCF-7, MCF10A and MDA-MB-231 breast canc...

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Detalles Bibliográficos
Autores principales: Ahmadi, Saeedeh, Seraj, Mahmoud, Chiani, Mohsen, Hosseini, Seyedayin, Bazzazan, Saba, Akbarzadeh, Iman, Saffar, Samaneh, Mostafavi, Ebrahim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9753765/
https://www.ncbi.nlm.nih.gov/pubmed/36531115
http://dx.doi.org/10.2147/IJN.S384085
Descripción
Sumario:INTRODUCTION: Breast cancer is among the most prevalent mortal cancers in women worldwide. In the present study, an optimum formulation of letrozole, letrozole-loaded niosome, and empty niosome was developed, and the anticancer effect was assessed in in vitro MCF-7, MCF10A and MDA-MB-231 breast cancer cell lines. MATERIALS AND METHODS: Various niosomal formulations of letrozole were fabricated through thin-film hydration method and characterized in terms of size, polydispersity index (PDI), morphology, entrapment efficiency (EE%), release kinetics, and stability. Optimized niosomal formulation of letrozole was achieved by response surface methodology (RSM). Antiproliferative activity and the mechanism were assessed by MTT assay, quantitative real-time PCR, and flow cytometry. Furthermore, cellular uptake of optimum formulation was evaluated by confocal electron microscopy. RESULTS: The formulated letrozole had a spherical shape and showed a slow-release profile of the drug after 72 h. The size, PDI, and eEE% of nanoparticles showed higher stability at 4°C compared with 25°C. The drug release from niosomes was in accordance with Korsmeyer–Peppa’s kinetic model. Confocal microscopy revealed the localization of drug-loaded niosomes in the cancer cells. MTT assay revealed that all samples exhibited dose-dependent cytotoxicity against breast cancer cells. The IC(50) of mixed formulation of letrozole with letrozole-loaded niosome (L + L(3)) is the lowest value among all prepared formulations. L+L(3) influenced the gene expression in the tested breast cancer cell lines by down-regulating the expression of Bcl(2) gene while up-regulating the expression of p53 and Bax genes. The flow cytometry results revealed that L + L(3) enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cell lines compared with the letrozole (L), letrozole-loaded niosome (L(3)), and control sample. CONCLUSION: Results indicated that niosomes could be a promising drug carrier for the delivery of letrozole to breast cancer cells.