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.
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