Preparation of Curcumin Solid Lipid Nanoparticles Loaded with Flower-Shaped Lactose for Lung Inhalation and Preliminary Evaluation of Cytotoxicity In Vitro.

The purpose of this study is to design a flower-shaped lactose loaded curcumin solid lipid nanoparticles dry powder inhaler and characterize it to improve the solubility and dissolution rate of curcumin in lung. Curcumin solid lipid nanoparticles (Cur-SLNs) were prepared by solvent evaporation method, and then they were micronized by freeze-drying technology. Finally, Cur-SLN micropowder obtained by freeze-drying was mixed with flower-shaped lactose (FL) at a ratio of 2 : 1 and then passed through a 200-mesh sieve to obtain Cur-SLN-FL powder. Tween-80 was selected as the surfactant to inhibit the aggregation of drug solid lipid nanoparticles. Under the optimum conditions, the solid lipid nanoparticles (SLN) were relatively spherical, with an average particle size of 14.7 nm, narrow distribution, Zeta potential of -22.5 mV, encapsulation efficiency of 90.21%, and drug loading of 8.56%. According to the particle size, PI, Zeta potential, drug loading (LC%), encapsulation efficiency (EE%), morphology, and in vitro release characteristics, the prescription of solid lipid nanoparticles was screened. Dry powder inhaler (DPI) was characterized by differential scanning calorimetry, scanning electron microscopy, particle size, density, and in vitro release performance. Its cytotoxicity to mouse fibroblasts (L929) and human normal lung epithelial cells (BEAS-2B) in vitro was investigated, and its safety for pulmonary inhalation was preliminarily determined. FTIR analysis shows that the micronized Cur-SLN-FL has the same chemical structure as FL. FTIR and DSC analysis confirmed that the characteristic absorption peak of curcumin was not found in Cur-SLN-FL, showing similar structure to SLN and FL. In addition, curcumin was coated in solid lipid nanoparticles to make powder mist, which increased its drug loading, kept its aerodynamic particle size (4.03 ± 0.40) m, and significantly improved its drug release performance in artificial lung fluid. In vitro cytotoxicity test results confirmed that Cur-SLN-FL was less toxic to BEAS-2B cells than L929 cells. Therefore, curcumin was prepared into solid lipid nanoparticles by emulsion evaporation-low temperature solidification method and then micronized and mixed with FL to prepare curcumin solid lipid nanoparticle powder mist loaded with flower-shaped lactose. The process is simple and feasible, and it has better safety performance for lung cells, which is expected to become a safe and effective delivery system for pulmonary inhalation drugs.