A Polyol Dilution Method for Mass Production of Liposomes

We developed a polyol dilution method for the mass production of liposomes. This method consists of the mixing of membrane components (and lipophilic drugs) with a water-soluble, non-volatile organic solvent (glycerin, propylene glycol, etc.), followed by the dispersal of the mixture in an aqueous medium. The polyols which can be used in this method are physiologically acceptable even when the final preparation is administered intravenously into the human body. Liposomes prepared by this polyol dilution method (PD-liposomes) were characterized in comparison with the traditional liposomes known as Bangham's liposomes. Incorporation of cholesterol and charged lipids was confirmed by gel filtration chromatography, differential scanning calorimetry and zeta potential measurements. Homogeneous size distribution of PD-liposomes could be obtained by an extrusion technique. The encapsulation efficiency of sodium salicylate and dextran T-40 as water-soluble model drugs was 4-18%, while a higher encapsulation efficiency could be achieved if the concentrated dextran aqueous solution was previously added to the lipids-polyol mixture and kneaded. This method was applied for the preparation of nascent HDL and liposomal doxorubicin. The polyol dilution method is considered a convenient and valuable technique for the mass production of liposomes.