![]() ![]() ![]() Qu is a plant flavonoid of polyphenols, which has shown beneficial therapeutic effects against different types of cancers as breast, lung, nasopharyngeal, kidney, colorectal, prostate, pancreatic, and ovarian cancer. LTZ is a nonsteroidal aromatase inhibitor that can slow down the progress of certain types of breast cancer cells by decreasing the amount of estrogen produced. In the current study, the combination therapy of the aromatase inhibitor (LTZ) and polyphenolic flavonoids (Qu) will be investigated. The combination of the aromatase inhibitor LTZ with antiestrogen (fulvestrant), multi-kinase inhibitor (sorafenib), COX-2 inhibitor (celecoxib), polyphenolic flavonoids (quercetin, Qu) were previously studied and showed high and synergistic efficacy on the apoptosis and proliferation inhibition of breast cancer cells. Aromatase inhibitors are associated with resistance development therefore, drug combination strategies may bypass or delay resistance and improve treatment outcome. The transdermal patches of different aromatase inhibitors were developed for site-specific delivery in the breast cancer region to achieve high local drug concentrations. Therefore, beyond the more patient compliance achieved with the drug transdermal delivery, it provides high drug concentration at the site of application and low plasma drug concentration with reduced systemic side effects. Additionally, local estrogen inhibition could overcome the side effects reported from patients under hormonal therapy, resulting from depletion of the circulating estrogen as hot flashes and bone deterioration. Therefore, the specific inhibition of estrogen levels in the breast tissue could be more beneficial for disease management. Further studies proved that almost 100% of the biologically active estrogen is produced locally. In postmenopausal women, tissue estrogen concentrations are superior to plasma estrogen concentration. Accordingly, the estrogen-dependent progression of most breast cancers could be disrupted by drugs interfering with estrogen binding to estrogen receptors (as tamoxifen), downregulating ER (as fulvestrant) or inhibiting estrogen production using aromatase inhibitors (as letrozole LTZ). Since most breast cancers (80%) are estrogen receptor–positive (ER+), the growth and survival of cancerous breast epithelial cells are promoted by estrogen through binding to ER. Early detection through breast screening (mammogram) and advanced therapeutic strategies result in better prognosis and improved survival rates. In case of local stage tumor, the 5-year survival rate is 99%, compared to 86% and 27% at regional stage and metastatic breast cancer, respectively. These results confirm the potential of LTZSPs and QuSPs combination for transdermal delivery of drugs for enhanced breast cancer management.īreast cancer, the most invasive cancer among women globally, is the primary cause of cancer-related deaths among women worldwide. The LTZSPs and QuSPs combination was superior to the individual treatments and the soluble free drugs in terms of in vitro cytotoxicity, cell cycle analysis, and ROS studies. Further, we evaluated the in vitro cytotoxicity, cell cycle analysis, and intracellular reactive oxygen species (ROS) of the combination therapy of letrozole and quercetin either in soluble form or loaded in spanlastics against MCF-7 breast cancer cells. The in vitro release study of LTZ and Qu from the selected formulations showed a sustained drug release for 24 h with reasonable flux and permeation through the rat skin. The prepared spherical LTZSPs and QuSPs had average particle sizes ranged between 129–310 nm and 240–560 nm, respectively, with negative surface charge and high LTZ and Qu encapsulation (94.3–97.2% and 97.9–99.6%, respectively). The optimized formulations were further examined using transmission electron microscopy, Fourier transform infrared spectroscopy, in vitro drug release and ex vivo skin permeation studies. The spanlastics were evaluated for their average particles size, surface charge, and percent encapsulation efficiency. In the current study, we prepared letrozole-(LTZSPs) and quercetin-loaded spanlastics (QuSPs) using different edge activators-Tween 80, Brij 35, and Cremophor RH40-with different concentrations. Combinatorial treatment could overcome the resistance and improve the outcome of breast cancer treatment. However, drug resistance limits the benefits of this approach. Most breast cancers (80%) are estrogen receptor–positive, indicating that disease progression could be controlled by estrogen inhibition in the breast tissue. Breast cancer is the most widespread cancer in women with rising incidence, prevalence, and mortality in developed regions. ![]()
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