Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes

Abstract

Yumeng Wei,1,* Jianmin Guo,2,* Xiaoli Zheng,2,* Jun Wu,3 Yang Zhou,1 Yu Yu,4 Yun Ye,1 Liangke Zhang,4 Ling Zhao11School of Pharmacy, 2Institute of Basic Medical Sciences, Luzhou Medical College, Luzhou City, Sichuan Province, People’s Republic of China; 3Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Greenville, SC, USA; 4School of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workAbstract: Baicalin (BA) is a major constituent of Scutellaria baicalensis Georgi, a medicinal herb. Previous pharmacokinetic studies of BA showed its low oral bioavailability. The aim of the present study was to develop a novel BA-loaded liposome (BA-LP) to enhance oral bioavailability. BA-LP, composed of BA, Tween® 80, Phospholipon® 90H, and citric acid at weight ratio of 96/50/96/50, respectively, was prepared by the effervescent dispersion technique and characterized in terms of morphology, size, zeta potential, encapsulation efficiency, and the in vitro release. Pharmacokinetics and biodistribution studies were carried out in rats after oral administration of BA-LP and a carboxymethyl cellulose suspension containing BA (BA-CMC) as a control. BA-LP exhibited a spherical shape by transmission electron microscopy observation. BA-LP had a mean particle size of 373±15.5 nm, zeta potential of -20.1±0.22 mV, and encapsulation efficiency of 82.7%±0.59%. The BA-LP showed a sustained-release behavior, and the in vitro drug-release kinetic model fit well with the Weibull distribution equation: lnln (1/(1-Q)) =0.609 lnt -1.230 (r=0.995). The oral bioavailability and the peak concentration of the BA-LP was threefold and 2.82-fold that of BA-CMC, respectively. The in vivo distribution results indicated that drug concentrations were significantly increased in the liver, kidney, and lung in the case of BA-LP, which were 5.59-fold, 2.33-fold, and 1.25-fold higher than those of BA-CMC, respectively. In conclusion, the study suggested that BA-LP might be a potential oral drug delivery system to improve bioavailability of BA. Keywords: nanoliposomes, bioavailability, nanoliposomes, in vitro release, bioavailability, in vivo evaluation