Evaluation of circulation profiles of liposomes coated with hydrophilic polymers having different molecular weights in rats.

The purpose of this study was to evaluate the circulating properties of liposomes coated with modified polyvinyl alcohol (PVA-R) having different molecular weights (6000, 9000 and 20000). The size controlled liposomes (egg phosphatidylcholine (or distearoylphosphatidylcholine):cholesterol=7:3 in a molar ratio) were prepared by the hydration method followed by sonication. Polymer coated liposomes were prepared by just mixing the resultant liposomal suspension and a polymer solution. The effects of polymer coating were evaluated by measuring the circulation time of the injected liposomes after i.v. administration in rats and the dispersing property of the liposomes in a biological condition. The circulation of the PVA-R coated liposomes was prolonged with increasing the molecular weight of PVA-R. The aggregation and/or fusion of the liposomes in the presence of serum in vitro was also depressed more by coating the liposomes with PVA-R having higher molecular weight. There was a good correlation between the circulation time and the physical stability of non-coated and the various PVA-R coated liposomes. The prolonged circulation time of PVA-R (molecular weight: 20000) coated liposomes (ca. 1.3 mol% coating) was comparable to that of a stealth liposome prepared with 8 mol% of DSPE-PEG (molecular weight of PEG: 2000).