In vitro and in vivo stability of polymerized mixed liposomes composed of 2,4-octadecadienoyl groups of phospholipids

The in vitro stability under freeze-thawing procedures, and in vivo degrada tion, in rat spleen, of two types of polymerized liposomes were examined: 1 ,2-bis-[(2E, 4E) - octadecadienoyl] - sn - glycero -3- phosphocholine (DODP C) and 1-acyl-2-[(2E, 4E)-octadecadienoyl]-snglycero-3-phosphocholine (AODP C) were used as polymerizable phospholipids. The lipid composition of the l iposomes was prepared as DODPC/Chol/SA (Chol = cholesterol, SA = stearicaci d), AODPC/Chol/SA (7/7/2 by molar ratio), AODPC/DPPC/Chol/SA (3.5/3.5/7/2 b y molar ratio). The liposomes were extruded through a 0.2 mu m polycarbonat e- filter to obtain the approximate particle size of 0.2 mu m, and then irr adiated with gamma-rays. Hemoglobin-encapsulated liposomes were also prepar ed in the same manner with concentrated hemoglobin (Hb) solution. The DODPC /Chol/SA liposome exhibited no trace of particle size change nor Hb leakage . Although not as excellent as the former, the AODPC-base liposome showed s lightly diameter change (below 7.5%) with a substantial abatement of Hb lea kage (<3.5%). Transmission electron microscopy observation of spleens also revealed move efficient degradability rc,with AODPC/DPPC/Chol/SA liposome t han with DODPC/Chol/SA liposome. Hb-encapsulated AODPC/DPPC/Chol/SA liposom e, after five freeze-thawing cycles, attained an Hb leakage below 3.5% with a particle size change of 0.7-7.5%, and reduced the spleen retention compa red with the DODPC-base liposome. These results suggest that AODPC/DPPC/Cho l/SA liposome can De used as a long-term preservable blood substitute. Copy right (C) 2000 John Wiley & Sons, Ltd.