International Journal of Nanomedicine (Dec 2022)

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

  • Ahmadi S,
  • Seraj M,
  • Chiani M,
  • Hosseini S,
  • Bazzazan S,
  • Akbarzadeh I,
  • Saffar S,
  • Mostafavi E

Journal volume & issue
Vol. Volume 17
pp. 6233 – 6255

Abstract

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Saeedeh Ahmadi,1 Mahmoud Seraj,2 Mohsen Chiani,1 Seyedayin Hosseini,3 Saba Bazzazan,4 Iman Akbarzadeh,1 Samaneh Saffar,4 Ebrahim Mostafavi5,6 1Department of Nano Biotechnology, New Technology Research Group, Pasteur Institute of Iran, Tehran, Iran; 2Integrative Research Laboratory, Islamic Azad University of Medical Sciences, Tehran, Iran; 3School of Medicine, Sh Beheshti University of Medical Sciences, Tehran, Iran; 4Core Facility Lab, Pasteur Institute of Iran, Tehran, Iran; 5Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA; 6Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USACorrespondence: Ebrahim Mostafavi, Email [email protected], [email protected]; Mohsen Chiani, Email [email protected]: 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 IC50 of mixed formulation of letrozole with letrozole-loaded niosome (L + L3) is the lowest value among all prepared formulations. L+L3 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 + L3 enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cell lines compared with the letrozole (L), letrozole-loaded niosome (L3), and control sample.Conclusion: Results indicated that niosomes could be a promising drug carrier for the delivery of letrozole to breast cancer cells.Graphical Abstract: Keywords: breast cancer, niosome, letrozole, drug delivery system, anticancer

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