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Antimicrobial Agents and Chemotherapy, August 1998, p. 1878-1888, Vol. 42, No. 8
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Plasma Lipoprotein Distribution of Liposomal Nystatin Is Influenced by Protein Content of High-Density Lipoproteins

Shawn M. Cassidy, Frank W. Strobel, and Kishor M. Wasan*

Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3

Received 29 October 1997/Returned for modification 26 April 1998/Accepted 1 May 1998

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 µg/ml) for 5 min at 37°C. 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.

* Corresponding author. Mailing address: Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall Ave., Vancouver, British Columbia, Canada V6T 1Z3. Phone: (604) 822-4889. Fax: (604) 822-3035. E-mail: Kwasan{at}unixg.ubc.ca.

Antimicrobial Agents and Chemotherapy, August 1998, p. 1878-1888, Vol. 42, No. 8
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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