Formulation Optimization of Leonurine Lipid Nanoparticles by Box-Behnken Response Surface Methodology

OBJECTIVE To optimize the formulation of leonurine lipid nanoparticles.METHODS The leonurine lipid nanoparticles were prepared by pH-gradients method coupled with reverse evaporation method.Final drug concentration, drug-lipid ratio, cholesterol and lipid ratio were selected as influences factors, the formulation was optimized by Box-Behnken response surface method with particle, the particle size, encapsulation efficiency and loading content as the evaluation parameters.The in vitro release was determined.RESULTS The optimal formulation parameters were as follows: the drug-lipid ratio was 9.8%, cholesterol and lipid ratio was 1.0% and the final drug concentration was 10 mg·mL^-1.The mean particle size, entrapment efficiency, and the drug loading were (83.9±5.6)nm, (73.3±2.2)% and (4.0±0.0)%, respectively.RSD of measured and predicted values were all less than 5%.In vitro release test results showed that leonurine lipid nanoparticles had a sustained release effect compared with the raw materials.CONCLUSION The Box-Behnken response surface method is simple and predictable, and have high encapsulation efficiency and drug loading of the obtained leonurine lipid nanoparticles, which meets the design requirements.