%0 Journal Article
%T Preparation, Characterization, and Pharmacokinetic Evaluation of Imperatorin Lipid Microspheres and Their Effect on the Proliferation of MDA-MB-231 Cells
%A Chunyan Wang
%A Guowei Zhao
%A Jing Zhang
%A Tao Tang
%A Wei Dong
%A Xinli Liang
%A Xulong Chen
%A Zhenggen Liao
%J Archive of "Pharmaceutics".
%D 2018
%R 10.3390/pharmaceutics10040236
%X Imperatorin is a chemical compound belonging to the linear furanocoumarins. Imperatorin is attracting considerable attention because of its antitumor, antibacterial, anti-inflammatory, and anticoagulant activities, inhibition of myocardial hypertrophy, and other pharmacological efficacies. However, imperatorin has limited water solubility and has better lipid solubility; thus, we decided to design and synthesize imperatorin lipid microspheres to optimize the preparation conditions. The aim was to develop and formulate imperatorin lipid microspheres through nanoemulsion technology and apply the response surface¨Ccentral composite design to optimize the imperatorin lipid microsphere formulation. The influence of the amounts of egg lecithin, poloxamer 188, and soybean oil for injection on the total percentage of the oil phase was investigated. The integrated effect of dependent variables, including particle size, polydispersity index, zeta potentials, drug loading, and encapsulation efficiency, was investigated. Data of overall desirabilities were fitted to a second-order polynomial equation, through which three-dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-Expert 8.06. Results indicated that the optimum preparation conditions were as follows: 1.39 g of egg lecithin, 0.21 g of poloxamer 188, and 10.57% soybean oil for injection. Preparation of imperatorin lipid microspheres according to the optimum experimental conditions resulted in an overall desirability of 0.7286, with the particle size of 168 ¡À 0.54 nm, polydispersity index (PDI) of 0.138 ¡À 0.02, zeta potentials of £¿43.5 ¡À 0.5 mV, drug loading of 0.833 ¡À 0.27 mg¡¤mL£¿1, and encapsulation efficiency of 90 ¡À 1.27%. The difference between the observed and predicted values of the overall desirability of the optimum formulation was in the range from 2.4% to 4.3%. Subsequently, scanning electron microscopy was used to observe the micromorphology of the imperatorin lipid microspheres, showing round globules of relatively uniform shape and sizes within 200 nm. The effect of imperatorin lipid microspheres on MDA-MB-231 proliferation was investigated by the MTT method. Furthermore, pharmacokinetics in Sprague-Dawley rats was evaluated using orbital bleeding. A sensitive and reliable liquid chromatography with the high-performance liquid chromatography (HPLC) method was established and validated for the quantification of imperatorin in rat plasma samples. The data were calculated by DAS (drug and statistics) Pharmacokinetic Software version 3.3.0
%K imperatorin
%K lipid microsphere
%K response surface methodology
%K pharmacokinetic
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321357/