Quality by design-based development and optimization of polymeric nanoparticles for co-administration of docetaxel and curcumin: In vitro characterization and preclinical evaluation

Docetaxel (DTX), a widely used chemotherapeutic agent for breast cancer, exhibits poor oral bioavailability due to low aqueous solubility and P-glycoprotein-mediated efflux. To overcome these limitations, docetaxel nanoparticles (DNPs) and curcumin nanoparticles (CNPs) composed of Eudragit RS100 and RL100 were developed and combined as a co-administration system (DCNPs). Five batches each of DNP and CNP were produced by the solvent evaporation method and optimized using a simplex lattice design to eventually produce DCNPs. Optimized DNPs exhibited particle size (PS) of 382.2 ± 14.20 nm, PDI of 0.405 ± 0.10, zeta potential (ZP) of 39.0 ± 4.30 mV, encapsulation efficiency (EE) of 86.65 ± 2.9%, and drug release at 24 h (D 24 h ) of 44.01 ± 2.1%, whereas optimized CNPs showed PS of 193.8 ± 7.30 nm, PDI of 0.248 ± 0.08, ZP of 34.0 ± 4.0 mV, EE of 80.33 ± 2.2%, and D 24 h of 49.20 ± 4.2%.The in vitro hemolysis assay demonstrated significantly ( p < 0.05 ) reduced erythrocyte toxicity of DCNPs compared with free DTX. Fluorescence imaging in MCF-7 cells revealed markedly enhanced intracellular uptake of DCNPs. In vivo pharmacokinetic studies in female wistar rats demonstrated significantly ( p < 0.05 ) higher AUC 0-ꚙ for DCNPs (114.41 ± 3 . 80 ng·h·mL −1 ) compared with DTX (95.07 ± 2.32 ng·h·mL −1 ) and DNPs (93.26 ± 3.58 ng·h·mL −1 ). Overall, this study demonstrated improved drug delivery and systemic exposure following co-administration of the separately optimized nanoparticles, supporting their potential for oral combination therapy.