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 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.

Preparation, Optimization and In-Vitro Evaluation of Curcumin-Loaded Niosome@calcium Alginate Nanocarrier as a New Approach for Breast Cancer Treatment.

Cancer is one of the most common causes of mortality, and its various treatment methods can have many challenges for patients. As one of the most widely used cancer treatments, chemotherapy may result in diverse side effects. The lack of targeted drug delivery to tumor tissues can raise the possibility of damage to healthy tissues, with attendant dysfunction. In the present study, an optimum formulation of curcumin-loaded niosomes with a calcium alginate shell (AL-NioC) was developed and optimized by a three-level Box-Behnken design-in terms of dimension and drug loading efficiency. The niosomes were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering. The as-formulated niosomes showed excellent stability for up to 1 month at 4 °C. Additionally, the niosomal formulation demonstrated a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 3). Cytotoxicity studies showed high compatibility of AL-NioC toward normal MCF10A cells, while significant toxicity was observed in MDA-MB-231 and SKBR3 breast cancer cells. Gene expression studies of the cancer cells showed downregulation of Bcl2, cyclin D, and cyclin E genes, as well as upregulation of P53, Bax, caspase-3, and caspase-9 genes expression following the designed treatment. Flow cytometry studies confirmed a significant enhancement in the apoptosis rate in the presence of AL-NioC in both MDA-MB-231 and SKBR3 cells as compared to other samples. In general, the results of this study demonstrated that-thanks to its biocompatibility toward normal cells-the AL-NioC formulation can efficiently deliver hydrophobic drugs to target cancer cells while reducing side effects.

Niosomal delivery of simvastatin to MDA-MB-231 cancer cells.

OBJECTIVE: The objective of this study was to use nano-niosomal formulations to deliver simvastatin as a poor-water soluble drug into breast cancer cells. SIGNIFICANCE: Our study focused on the problem associated with poor water-soluble drugs which have significant biological activity in vivo. METHODS: Different niosomal formulations of simvastatin were prepared and characterized in terms of morphology, size, encapsulation efficiency (EE), and release kinetic. Antiproliferative activity and the mechanism were assessed by quantitative real-time PCR and flow cytometry. Moreover, confocal microscopy was employed to analyze the cell uptake of simvastatin loaded niosomes to the cancerous cells. RESULTS: Size, polydispersity index (PDI), and EE of the best formulation were obtained as 164.8 nm, 0.232, and 97%, respectively. The formulated simvastatin had a spherical shape and showed a slow release profile of the drug after 72 h. Stability data elucidated an increase in mean diameter and PDI which was lower for 4 °C than 25 °C. Confocal microscopy showed the localization of drug loaded niosomes in the cancer cells. The MTT assay revealed both free drug and drug loaded niosomes exhibited a dose-dependent cytotoxicity against breast cancer cells (MDA-MB-231 cells). Flow cytometry and qPCR analysis revealed drug loaded niosomes exert their cytotoxicity on cancerous cells via regulation of apoptotic and anti-apoptotic genes. CONCLUSION: The prepared niosomal simvastatin showed good physicochemical and biological properties than free drug. Our study suggests that niosomal delivery could be considered as a promising strategy for the delivery of poor water-soluble drugs to cancer cells.