Design development and characterization of dutasteride and docetaxel loaded nanostructured lipid carriers for the treatment of prostate cancer in rats

Abstract

newline Background and Objective: Prostate cancer remains one of the leading causes of cancer-related mortality in men worldwide, necessitating the development of innovative therapeutic approaches. Current treatment modalities often suffer from poor drug bioavailability, systemic toxicity, and limited tumor penetration. This study aimed to design, develop, and characterize dual drug-loaded nanostructured lipid carriers (NLCs) incorporating dutasteride and docetaxel for enhanced prostate cancer therapy in a rat model. newlineMethods: Nanostructured lipid carriers were formulated using a hot high-pressure homogenization technique, employing a combination of solid and liquid lipids to create a stable matrix for drug encapsulation. Dutasteride, a 5and#945;-reductase inhibitor that reduces dihydrotestosterone levels, and docetaxel, a potent microtubule-stabilizing chemotherapeutic agent, were co-loaded into the NLC system. The formulation was optimized through a systematic approach evaluating various lipid ratios, surfactant concentrations, and processing parameters. Comprehensive characterization was performed including particle size analysis, zeta potential measurement, morphological examination using transmission electron microscopy, drug loading efficiency determination, and in vitro release kinetics assessment. The crystalline behavior of the lipid matrix was evaluated using differential scanning calorimetry and X-ray diffraction analysis. newlineResults: The optimized dual drug-loaded NLCs exhibited an average particle size of 185 ± 12 nm with a polydispersity index of 0.24, indicating uniform size distribution suitable for intravenous administration. The zeta potential was measured at -28.5 ± 3.2 mV, suggesting adequate colloidal stability. High encapsulation efficiencies were achieved for both drugs: 89.3 ± 4.1% for dutasteride and 92.7 ± 2.8% for docetaxel. In vitro release studies demonstrated sustained drug release profiles with approximately 78% of dutasteride and 82% of docetaxel released over 72 hours, following Higuchi kinetics model. The formulation maintained stability at 4°C for six months without significant changes in particle size or drug content. newline