IMPROVED LIPOSOMAL FORMULATIONS OF NUCLEOTIDES AND NUCLEOTIDE ANALOGUES

摘要

Disclosed are formulations for use in preparing efficient and stable liposomes for therapeutic use according to an extrusion process. These formulations are effective in increasing the capture efficiency and stability of the liposomes with respect to water soluble therapeutic nucleotides, such as AZT monophosphate. Effective formulation characteristics include the presence of unsaturated acyl chains in phospholipids and effective amounts of negatively charged phospholipids as well as sterols in the lipid phase, the use of hydration buffers having an approximately neutral or acidic pH, and a favorable formulation concentration of therapeutic agent. Disclosed also are processes for preparing liposome preparations by means of freeze-thaw and extrusion cycles, followed by filtration. Liposomes prepared by the extrusion process according to optimum formulations show high capture efficiency for nucleotides as well as extended stability with respect to leakage of nucleotides when exposed to serum.