PHYSICAL CHARACTERISTICS AND LIPOPROTEIN DISTRIBUTION OF LIPOSOMAL NYSTATIN IN HUMAN PLASMA

The physical characteristics and lipoprotein distribution of free nyst atin (NYS) and liposomal NYS (L-NYS) in human plasma were investigated , To determine the percentage of NYS that was lipid associated followi ng incubation in human plasma, C-18 reverse-phase extraction columns w ere used. To assess plasma drug distribution, NYS and L-NYS (20 mu g/m l) were incubated in human plasma for 5, 60, and 120 min at 37 degrees C. After each interval, plasma was removed and separated into its lip oprotein and lipoprotein-deficient plasma (LPDP) fractions by ultracen trifugation and assayed for NYS by high-pressure liquid chromatography . Further studies evaluated the liposome structure of L-NYS by filteri ng through a 0.14-mu m-pore-size microfilter before and after the addi tion of human plasma. When reconstituted L-NYS (mean particle diameter +/- standard deviation, 321 +/- 192 nm) was applied to a C-18 column, 67% +/- 4% of the initial NYS concentration was associated with the l ipid. When plasma samples containing L-NYS that had been incubated for 5 to 120 min at 37 degrees C were applied to C-18 columns, 66 to 76% of the NYS was lipid associated. Incubation of NYS in human plasma for 5 min at 37 degrees C resulted in 3% +/- 1% of the initial NYS concen tration incubated in the low-density lipoprotein (LDL) fraction, 23% /- 4% of that in the high-density lipoprotein (HDL) fraction, and 66% +/- 10% of that in the LPDP fraction, In contrast, the distribution of NYS following incubation of L-NYS in human plasma for 5 min was 13% /- 2% in the LDL fraction, 44% +/- 5% in the HDL fraction, and 42% +/- 5% in the LPDP fraction. Similar results were observed following 60 a nd 120 min of incubation. In addition, the liposome structure of L-NYS was quickly lost when mixed with plasma. These findings suggest that rapid disruption of the L-NYS structure upon incubation in human plasm a is consistent with its rapid distribution in plasma. The preferentia l distribution of NYS into the HDL fraction upon incubation of L-NYS m ay be a function of its phospholipid composition.