Development and characterization of liposomal disodium ascorbyl phytostanyl phosphates (FM-VP4).
The specific objectives of this project were (1) to develop liposomal disodium ascorbyl phytostanyl phosphate (FM-VP4) formulations, (2) to develop a liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) assay for quantification of FM-VP4 in liposomal formulations and plasma sample, and (3) to characterize liposomal FM-VP4 formulations by finding optimal drug-to-lipid ratios and determining the degradation of FM-VP4 in liposomes. Section 2 describes an LC/MS/MS assay developed for the identification and quantification of FM-VP4 in liposomal formulations to provide estimates of drug concentrations and encapsulation efficiency. The extra step of removing plasma proteins prior to LC/MS/MS assay yields an analysis of FM-VP4 in plasma samples. Section 3 describes experiments designed to find the optimal drug-to-lipid ratio for liposomal FM-VP4 formulations by comparing encapsulation efficiencies and varying the lipid compositions. Additionally, this section details our degradation studies to determine if liposomes have any protective effects on FM-VP4; these studies tested various lipid compositions at 37 degrees C in rabbit plasma. The mechanism of how FM-VP4 lowers low-density lipoprotein (LDL) cholesterol and total cholesterol levels in various animal models is presently unknown. However, before the mechanism of action could be studied, FM-VP4 first had to be delivered efficiently into plasma or cultured cell. The low systemic bioavailability and cellular uptake of FM-VP4 further suggested the importance of finding an efficient delivery vehicle for this drug. This project proposed a framework for such delivery and paves the way for further investigation into how FM-VP4 works in vivo and in vitro.
Ng
Agatha W K
AW
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Lukic
Tatjana
T
Pritchard
P Haydn
PH
Wasan
Kishor M
KM
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D008081:Liposomes; D010840:Phytosterols / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D011817:Rabbits
C445524:FM-VP4 compound; D008081:Liposomes; D010840:Phytosterols