Species difference in the disposition of liposomes among mice, rats, and rabbits: Allometric relationship and species dependent hepatic uptake mechanism

被引:28
作者
Harashima, H [1 ]
Komatsu, S [1 ]
Kojima, S [1 ]
Yanagi, C [1 ]
Morioka, Y [1 ]
Naito, M [1 ]
Kiwada, H [1 ]
机构
[1] NIIGATA UNIV,SCH MED,DEPT PATHOL 2,NIIGATA,NIIGATA 951,JAPAN
关键词
liposome; species difference; pharmacokinetics; drug delivery system;
D O I
10.1023/A:1016058724452
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. The species difference in the pharmacokinetics of liposomes was investigated in mice, rats and rabbits. Methods. Liposomes were intravenously injected at doses of 1, 10 and 100 (nmol/g body weight), and the time courses of liposomes in blood, liver and spleen were measured. Pharmacokinetic parameters were regressed as a function of body weight (BW) and dose of liposomes (D). The uptake mechanism of liposomes was also examined with the isolated perfused liver between rats and mice. Results. Mean residence time increased with the increase of BW and D of liposomes. This increase of mean residence time resulted from the decreased total body clearance, which was principally explained by the species difference in the hepatic uptake clearance (CLh) of liposomes. The parameter CLh was regressed well by a multiple regression as a function of BW and D. In this analysis, an exponent for BW was around 0.5, which clearly indicates that smaller animals have higher uptake clearance per unit BW. Immunohistochemical analysis revealed that there was no significant difference in the density of Kupffer cells among these species. This suggest that the species difference in CLh resulted not from the density of Kupffer cells but from the uptake ability of Kupffer cells amoung species. In the isolated perfused liver, the hepatic uptake of liposomes was mainly explained by opsonin dependent uptake in rats, while opsonin independent uptake in mice. Conclusions. These quantitative and qualitative information on the species difference of liposome disposition will provide an useful information for constructing a drug delivery system using liposomes.
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页码:1049 / 1054
页数:6
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