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

Abstract

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.

High-Affinity Extended Bisphosphonate-Based Coordination Polymers as Promising Candidates for Bone-Targeted Drug Delivery

“…The results show a decrease in the cell viability of MCF-7 cells treated with LET, with IC 50 of about 20 ± 3 μM after 72 h of treatment (Figure a and the SI). This IC 50 value is consistent with reports where similar seeding and treatment conditions were employed (IC 50 = ∼15–20 μM). , No significant cytotoxicity effects were observed for MDA-MB-231 and hFOB 1.19 cell lines treated with LET (Figure b,c; IC 50 > 200 μM after 72 h). Similar results were found for MCF-7 (Figure d), MDA-MB-231 (Figure e), and hFOB 1.19 (Figure f) cells treated with BPBPA (IC 50 > 200 μM after 72 h), with calculated IC 50 = 364 ± 3 μM for MCF-7 and 229 ± 5 μM for MDA-MB-231 cells treated with BPBPA at 72 h. IC 50 curves for the MCF-7, MDA-MB-231, and hFOB 1.19 cell lines treated with LET and BPBPA at 24, 48, and 72 h are shown in the SI.…”

“…This IC 50 value is consistent with reports where similar seeding and treatment conditions were employed (IC 50 = ∼15−20 μM). 62,63 No significant cytotoxicity effects were observed for MDA-MB-231 and hFOB 1.19 cell lines treated with LET (Figure 9b,c; IC 50 > 200 μM after 72 h). Similar results were found for MCF-7 (Figure 9d), MDA-MB-231 (Figure 9e), and hFOB 1.…”

“…In MCF-7 cells, LET can lead to cell apoptosis by inhibiting the aromatase enzyme, while in MDA-MB-231, LET might lead to diverse gene expression levels, affecting cell pro-apoptotic (stress or death) or antiapoptotic (mitogenic or survival) signals. [55][56][57]63,64 Previous studies demonstrate that encapsulated LET nanoparticles, once inside the MDA-MB-231 cells, showed upregulated expression of the proapoptotic genes caspase-3 and caspase-9. 63 The same study showed the downregulation of cyclin-D, cyclin-E, MMP-2, and MMP-9 genes in MDA-MB-231.…”

“…[55][56][57]63,64 Previous studies demonstrate that encapsulated LET nanoparticles, once inside the MDA-MB-231 cells, showed upregulated expression of the proapoptotic genes caspase-3 and caspase-9. 63 The same study showed the downregulation of cyclin-D, cyclin-E, MMP-2, and MMP-9 genes in MDA-MB-231. 64 These genes are involved in breast cancer growth and progression.…”

Polyvinyl Alcohol (PVA)-Based Nanoniosome for Enhanced in vitro Delivery and Anticancer Activity of Thymol

“…Another beneficial facet of herbal medicine compared to classical chemotherapy is its limited acute or chronic toxic side effects. 9,10 Although known to be less toxic, herbal medicine could be overdosed systematically to achieve appropriate pharmacodynamics, leading to unwanted toxicities. In addition, sustained release of therapeutic herbals is generally desired since it can address the low bioavailability of herbal medicine, mainly originating from their hydrophobic nature.…”