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

✍ Scribed by Kazuhiro Akama; Kouji Awai; Yoshihiro Yano; Satoru Tokuyama; Yoshio Nakano

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 613 KB
• Volume: 11
• Category: Article
• ISSN: 1042-7147
• DOI: 10.1002/1099-1581(200006)11:6<280::aid-pat942>3.0.co;2-c

✦ Synopsis

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]-snglycero-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 mm polycarbonate-filter to obtain the approximate particle size of 0.2 mm, and then irradiated with g-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 longterm preservable blood substitute.