DIVERSITY OF LIPID-BASED POLYENE FORMULATIONS AND THEIR BEHAVIOR IN BIOLOGICAL-SYSTEMS

Patients with cancer and infectious diseases often display dyslipidemi as that result in changes in their plasma lipoprotein-lipid compositio n. It is likely that the interactions of liposomal polyenes with plasm a lipoproteins may be responsible for the far different pharmacokineti cs and pharmacodynamics of these compounds when they are administered to infected patients rather than to animals or healthy volunteers. Amp hotericin B (AmpB) and nystatin are examples of such polyenes. Amphote ricin B initially distributes with the high-density lipoprotein (HDL) fraction upon incubation in plasma. Over time, AmpB redistributes from HDLs to low-density lipoproteins (LDLs). This redistribution appears to be regulated by lipid transfer protein. However, when AmpB is incor porated into liposomes composed of negatively or positively charged ph ospholipids, not only is the capability of LTP to transfer AmpB from H DL to LDL diminished, but AmpB remains retained with only the HDL frac tion. However, when liposomal nystatin is incubated in plasma, over 50 % of nystatin distributes with HDLs. Over time, nystatin redistributes from HDL to the lipoprotein-deficient plasma fraction, which is compo sed of mainly aqueous plasma proteins. The lipid composition selected for the drug appears to be a vital constituent in regulating the drug' s interaction with biological fluids, Furthermore, liposome (or liposo mal particle) size, fluidity, and other physiochemical characteristics also play a role in altering the pharmacokinetics and pharmacological effects of lipid-based drug formulations. Armed with this understandi ng, a rational approach to clinical development of these formulations could be facilitated.