Optimization of atorvastatin and quercetin-loaded solid lipid nanoparticles using Box-Behnken design

<b>Aim:</b> The study explores the synergistic potential of atorvastatin (ATR) and quercetin (QUER)- loaded solid lipid nanoparticles (SLN) in combating breast cancer. <b>Materials &amp; methods:</b> SLNs were synthesized using a high-shear homogenization method and optimized using Box-Behnken design. The SLNs were characterized and evaluated for their <i>in vitro</i> anticancer activity. <b>Results:</b> The optimized SLN exhibited narrow size distribution (PDI = 0.338 ± 0.034), a particle size of 72.5 ± 6.5 nm, higher entrapment efficiency (&lt;90%), sustained release and spherical surface particles. The <i>in vitro</i> cytotoxicity studies showed a significant reduction in IC₅₀ values on MDA-MB-231 cell lines. <b>Conclusion:</b> We report a novel strategy of repurposing well-known drugs and encapsulating them into SLNs as a promising drug-delivery system against breast cancer. Drug repurposing presents a viable approach for advancing cancer treatment by utilizing existing drugs with established safety records and biological effects. The present study reports on the development and comprehensive investigation of a dual drug-loaded system (containing both quercetin and atorvastatin) as an innovative drug-delivery platform for the effective treatment of breast cancer. Atorvastatin is primarily linked to altering lipogenesis by which it is able to induce apoptosis, suppress angiogenesis and inhibit tumor cell proliferation and metastasis. Along with quercetin, a naturally occurring flavonoid also complements atorvastatin by disrupting metabolic processes like fatty acid and cholesterol synthesis thereby acting as an anticancer agent. Box-Behnken design was used to prepare and optimize dual drug-loaded solid lipid nanoparticles (SLN) (atorvastatin and quercetin) with the hypothesis that this would solve the issue with single therapies and enhance their therapeutic outcomes. Advanced analytical techniques including dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder x-ray diffraction, field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM) were used to characterize the optimized SLN. A sensitive and robust reversed phase-high performance liquid chromatography (RP-HPLC) method was developed for simultaneous estimation of both the drugs from the SLN matrix and to observe their dissolution behavior. A sustained release profile that outperformed the drugs from the SLN matrix and had release kinetics that followed the Higuchi model was revealed by <i>in vitro</i> drug-release research. The <i>in</i>-<i>vitro</i> cytotoxicity study demonstrated the synergistic effect of atorvastatin and quercetin SLNs against MDA-MB-231, surpassing the efficacy of the individual drug effect.