Assembly of nanostructured lipid carriers loaded gefitinib and simvastatin as hybrid therapy for metastatic breast cancer: Codelivery and repurposing approach

Abstract

AbstractBreast cancer represents a life‐threatening problem globally. The major challenge in the clinical setting is the management of cancer resistance and metastasis. Hybrid therapy can affect several cellular targets involved in carcinogenesis with a lessening of adverse effects. Therefore, the current study aims to assemble, and optimize a hybrid of gefitinib (GFT) and simvastatin (SIM)‐loaded nanostructured lipid carrier (GFT/SIM‐NLC) to combat metastatic and drug‐resistant breast cancer. GFT/SIM‐NLC cargos were prepared using design of experiments to investigate the impact of poloxamer‐188 and fatty acids concentrations on the physicochemical and pharmaceutical behavior properties of NLC. Additionally, the biosafety of the prepared GFT/SIM‐NLC was studied using a fresh blood sample. Afterward, the optimized formulation was subjected to an MTT assay to study the cytotoxic activity of GFT/SIM‐NLC compared to free GFT/SIM using an MCF‐7 cell line as a surrogate model for breast cancer. The present results revealed that the particle size of the prepared NLC ranged from (209 to 410 nm) with a negative zeta potential value ranging from (−17.2 to −23.9 mV). Moreover, the optimized GFT/SIM‐NLC formulation showed favorable physicochemical properties and promising lymphatic delivery cargos. A biosafety study indicates that the prepared NLC has a gentle effect on erythrocyte hemolysis. Cytotoxicity studies revealed that GFT/SIM‐NLC enhanced the killing of the MCF‐7 cell line compared to free GFT/SIM. This study concluded that the hybrid therapy of GFT/SIM‐NLC is a potential approach to combat metastatic and drug‐resistant breast cancer.