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In vitro and in vivo stability of polymerized mixed liposomes composed of 2,4‐octadecadienoyl groups of phospholipids
Authors:Kazuhiro Akama  Kouji Awai  Yoshihiro Yano  Satoru Tokuyama  Yoshio Nakano
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.
Keywords:polymerizable phospholipid  liposome  hemoglobin  freeze–  thawing  TEM
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