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.

A passive split-and-recombine micromixer was developed based on the concept of lamellar structure and advection mixing type for a serpentine structure. The flow patterns and mixing performance were analyzed using numerical simulation in Reynolds number range of 10≤ Reynolds ≤170. Two design variables, defining the shape of the split-and-recombine branch, were optimized by the local energy dissipation rate as the objective function. The reduction of computation time and the absence of numerical diffusion were the advantages of using the energy dissipation rate as the objective function. At each Reynolds number, 64 sample data was generated on the design space uniformly. Then a model was used based on the Radial basis neural network for the prediction of the objective function. The optimum values of the design variables within the constraint range were found on the response surface. The optimization study was performed at five Reynolds numbers of 10, 50, 90, 130, 170 and the mixing index was improved 0.156, 0.298, 0.417, 0.506, and 0.57, respectively. The effect of design variables on the objective function and the concentration pattern was presented and analyzed. Finally, the mixing characteristic of the split-and-recombine micromixer was studied in a wide range of Reynolds number and the flow was categorized to stratify and show the vortex regime based on the Reynolds number. The optimized split-and-recombine micromixer could be integrated by any system depending on the desired velocity and Reynolds number.

This study aimed to improve the anticancer activity of letrozole through a niosomal formulation. Optimized niosomal formulation of letrozole was achieved by response surface methodology (RSM). The niosomes were well-characterized by several methods. The anticancer activity and its mechanism were studied in MCF-7 and MDA-MB-231 breast cancer cells. The release of the drug from the niosomes was according to the Kors Meyer-Peppa kinetic model. The niosomes were stable with high encapsulation efficiency. Significant higher anticancer activity and more induction of apoptosis were obtained for niosomal letrozole. Results indicated that niosomes could be a promising drug carrier for delivery of letrozole to breast cancer cells.