Surface-modified amikacin-liposomes: Organ distribution and interaction with plasma proteins

被引:18
作者
Bucke, WE
Leitzke, S
Diederichs, JE
Borner, K
Hahn, H
Ehlers, S
Muller, RH
机构
[1] Free Univ Berlin, Inst Pharmazeut Technol Biopharm & Biotechnol, Dept Pharmaceut Biopharmaceut & Biotechnol, D-12169 Berlin, Germany
[2] Free Univ Berlin, Klinikum Benjamin Franklin, Inst Infekt Hedrizin, D-12203 Berlin, Germany
[3] Free Univ Berlin, Klinikum Benjamin Franklin, Inst Klin Chem & Klin Biochem, D-12200 Berlin, Germany
关键词
amikacin; liposomes; opsonisation; organ distribution; protein adsorption; 2-D PAGE;
D O I
10.3109/10611869808995863
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Amikacin-loaded liposomes were produced and surface-modified by adsorption of PEG 4000, Tween 80, poloxamer 407 and gelatin. The organ distribution was studied in mice by analysing the amikacin content in liver, spleen, lung, kidneys and serum. Highest serum levels were obtained with the PEG-and Tween 80 modified liposomes (at 2 hours p.inj.). Modification of the liposomes with gelatin as opsonization promoting agent distinctly increased the amikacin concentration in the liver from 36 to 66 mg/kg. Highest spleen concentrations were observed with non-modified and poloxamer 407 liposomes (242 mg/kg and 248 mg/kg, respectively), The data suggest that modification by a simple adsorption process is sufficient to effectively alter the organ distribution. The liposomes differing in organ distribution exhibited also different plasma protein adsorption patterns, up to 115 spots were detected by 2-D PAGE. Hydrophilic albumin was present in a cone. of appr. 80% on liposomes modified with ethoxylated compounds. On the gelatin liposomes, 14% of alpha-2-Macroglobulin were adsorbed which is a protein typically found on particles rapidly cleared by the RES. IgM, Apo A-I, Apo C-II and alpha-1-Antitrypsin were other detected proteins.
引用
收藏
页码:99 / 108
页数:10
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