Preparation of folate-targeted Ergosta-4,6,8(14),22-tetraen-3-one liposomes and its evaluation in vitro and pharmacokinetic studies
- Author:
Xu-Hua LIANG
1
Author Information
1. School of Chemical Engineering
- Publication Type:Journal Article
- Keywords:
Cytotoxicity;
Ergosta-4,6,8(14),22-tetraen-3-one;
Folate;
Pharmacokinetic;
Slow release capacity;
Target activity
- From:
Chinese Pharmaceutical Journal
2012;47(12):979-983
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE: To prepare folate-conjugated ergosta-4,6,8,22-tetraen-3-one liposomes(FLE). Then to study the release feature of FLE in vitro and the eytotoxieity and targeting ability of it via folate receptor-mediated endocytosis on tumor cells in vitro. Pharmacokinetic characterization was also studied in rats. METHODS The characteristics were measured by transmission electron microscope(TEM), laser light scattering granularity equipment and HPLC. Dialytic method was used to determine ergone release rate of FLE in vitro. The cytotoxicity and targeting ability of FLE on HeLa in vitro was measured by MTT assay. The concentrations of ergone in plasma of rats and their pharmacokinetic behaviors after oral administration were studied by HPLC. The pharmacokinetic parameters were computed by software DAS2.0. RESULTS: The prepared FLE was round and uniform, and the mean particle size was 112 nm. The encapsulating efficiency of it reached 73%. The experiment of drug release in vitro follows Higuchi releasing process and showed significant sustained-release feature. The IC50 of ergone, LE and FLE was 10, 14, 5 μg · mL-1, respectively. Compared with ergone solution, AUC in FLE had increased significantly. And the residence time of ergone was prolonged. CONCLUSION: The FLE were characterized by sustained-release performance, target recognition, and low toxic and side effect and did improve the bioavailability of ergone significantly. It can also be expected to be used for tumor by targeting therapy.
