title: Preparation, Properties and Preclinical Pharmacokinetics of Low Molecular Weight Heparin-modified Isoliquiritigenin-loaded Solid Lipid Nanoparticle.
abstract: Low molecular weight heparin-modified isoliquiritigenin-loaded solid lipid nanoparticle (LMWH-ISL-SLN) was developed for injective application. The morphological observation, particle diameter and zeta potential of LMWH-ISL-SLN were characterized using transmission electron microscopy (TEM) and a Malvern Zetasizer. Its entrapment efficiency (EE) and drug loading (DL) were determined by ultracentrifuge. Thein-vitrorelease experiments were performed by dialysis technique. The cytotoxic effects of LMWH-ISL-SLN on Hep-G2 cell lines were determined using an MTT assay. Pharmacokinetic and tissue distribution studies were conducted in kunming mice after intravenous administration of LMWH-ISL-SLN. The average drug entrapment efficiency for LMWH-ISL-SLN was (99.80 ± 3.27)%, drug loading was (18.68 ± 1.51)%, mean particle size was (217.53 ± 4.86) nm and zeta potential was (-18.24 ± 2.47) mV. Thein-vitrorelease experiments demonstrated isoliquiritigenin release from LMWH-ISL-SLN was in line with Weibull's distribution law. Hemolysis test and dose-related toxic effects proved that LMWH-ISL-SLN was a safe and non toxic product when given by intravenous injection. The pharmacokinetics results of LMWH-ISL-SLN showed that the area under the concentration-time curve (AUC0→∞)of LMWH-ISL-SLN was greater than that for the isoliquiritigenin solution in plasma. Tissue distribution study indicated that ISL were mainly distributed in the liver and lung. In conclusion, low molecular weight heparin-modified SLN system is a promising carrier for the intravenous delivery of ISL.
authors.affiliation: School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Drug Clinical Trial Institution, the First Hospital of Lanzhou University,1 Donggang West Road, Lanzhou 730000, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Qiao
authors.affiliation: School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, the First Hospital of Lanzhou University,1 Donggang West Road, Lanzhou 730000, China.
authors.forename: Huxiong
authors.initials: H
authors.lastname: Xia
authors.affiliation: School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Shi
keywords: Isoliquiritigenin; Low molecular weight heparin; Pharmacokinetics; Solid lipid nanoparticle; Sustained release