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

Abstract

The in vitro stability, under freeze–thawing procedures, and in vivo degradation, in rat spleen, of two types of polymerized liposomes were examined: 1,2-bis-[2E, ­4E) - octadecadienoyl] - sn - glycero - 3 - phosphocholine (DODPC) and 1-acyl-2-[(2E, 4E)-octadecadienoyl]-sn-glycero-3-phosphocholine (AODPC) were used as polymerizable phospholipids. The lipid composition of the liposomes was prepared as DODPC/Chol/SA (Chol = cholesterol, SA = stearicacid), AODPC/Chol/SA (7/7/2 by molar ratio), AODPC/DPPC/Chol/SA (3.5/3.5/7/2 by molar ratio). The liposomes were extruded through a 0.2 µm polycarbonate- filter to obtain the approximate particle size of 0.2 µm, and then irradiated with γ-rays. Hemoglobin-encapsulated liposomes were also prepared 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 slightly diameter change (below 7.5%) with a substantial abatement of Hb leakage (<3.5%). Transmission electron microscopy observation of spleens also revealed more efficient degradability with AODPC/DPPC/Chol/SA liposome than with DODPC/Chol/SA liposome. Hb-encapsulated AODPC/DPPC/Chol/SA liposome, 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 compared with the DODPC-base liposome. These results suggest that AODPC/DPPC/Chol/SA liposome can be used as a long-term preservable blood substitute. Copyright © 2000 John Wiley & Sons, Ltd.