Preparation and Optimization of Leuprolide Acetate Nanoparticles Using Response Surface Methodology: and Evaluation.

This study aims to develop optimized leuprolide acetate (LA) nanoparticles (NPs) for intranasal delivery in the treatment of Alzheimer's disease. Box-Behnken Design was used to optimize LA polylactide--glycolic acid (PLGA) NPs. The independent variables chosen were PLGA concentration, surfactant concentration, and the ratio of water to oil phase, whereas the dependent variables were particle size and % entrapment efficiency. The optimized NPs were evaluated by drug release study, diffusion study, histopathology study, hemolytic stability study, and stability in simulated nasal fluid (SNF). The optimized NPs had particle size of 182.6 ± 1.5 nm, polydispersity index (0.3), % entrapment efficiency (77.3 ± 0.6), and zeta potential (-5.6 mv ±0.2). The drug release indicated 96% of pure drug release in 6 h, whereas only 66.35% of the drug was released from the optimized formulation at 48 h. The diffusion study indicated an apparent permeability coefficient of 5.0 + 0.3 × 10 for drug-containing NPs, which was higher than for plain drug solution (2.0 + 0.2 × 10). Sheep nasal toxicity and hemolytic study proved the safety of formulation. The optimized NPs were found to be stable in SNF. Thus, nanoparticulate formulation of LA was optimized by quality by design approach.