The proliposome-liposome method is based on the conversion of the initial proliposome preparation into a liposome dispersion by dilution with the aqueous phase, This technique is characterized by an extremely high entrapment efficiency and is suitable for the encapsulation of a wide range of drugs with different water and alcohol solubility. A description of a home-made stirred thermostated cell and its linkup with an FPLC system for a rapid and automated preparation of multilamellar liposomes under strictly controlled conditions (temperature, dilution rate, and schedule) is presented, The highly reproducible procedure yields multilamellar liposomes with a high encapsulation efficiency for various drugs. Carboxyfluorescein, as a model hydrophilic compound, was entrapped with an efficiency of 81 +/- 2%. The antibiotics neomycin and gentamycin were entrapped with efficiencies of 65 and 69%, respectively. Synthetic immunomodulators adamantylamide dipeptide, muramyl dipeptide, and beta-D-GlcNAc-norMurNAc-L-Abu-D-isoGln were entrapped with efficiencies of 87, 62, and 85%, respectively, The photosensitizer mesotetra-(parasulfophenyl)-porphin was entrapped with an efficiency of 65%. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up and linked with secondary processing methods, such as pressure extrusion through polycarbonate filters. (C) 1997 Academic Press.
