Plasma lipoprotein distribution of liposomal nystatin is influenced by protein content of high-density lipoproteins.
The plasma lipoprotein distribution of free nystatin (Nys) and liposomal nystatin (L-Nys) in human plasma samples with various lipoprotein lipid and protein concentrations and compositions was investigated. To assess the lipoprotein distributions of Nys and L-Nys, human plasma was incubated with Nys and L-Nys (equivalent to 20 microg/ml) for 5 min at 37 degreesC. The plasma was subsequently partitioned into its lipoprotein and lipoprotein-deficient plasma fractions by step-gradient ultracentrifugation, and each fraction was analyzed for Nys content by high-pressure liquid chromatography. The lipid and protein contents and compositions of each fraction were determined with enzymatic kits. Following the incubation of Nys and L-Nys in human plasma the majority of Nys recovered within the lipoprotein fractions was recovered from the high-density lipoprotein (HDL) fraction. Incorporation of Nys into liposomes consisting of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol significantly increased the percentage of drug recovered within the HDL fraction. Furthermore, it was observed that as the amount of HDL protein decreased the amounts of Nys and L-Nys recovered within this fraction decreased. These findings suggest that the preferential distribution of Nys and L-Nys into plasma HDL may be a function of the HDL protein concentration.
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
S M
SM
Cassidy
F W
FW
Strobel
K M
KM
Wasan
D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000032:analysis* / Q000378:metabolism; D008081:Liposomes; D009761:Nystatin / Q000008:administration & dosage / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008081:Liposomes; D009761:Nystatin; D002784:Cholesterol