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In vivo distribution and antitumor activity of heparin-stabilized doxorubicin-loaded liposomes.

Abstract：

:The purpose of this study was to investigate the effect of heparin conjugation to the surface of doxorubicin (DOX)-loaded liposomes on the circulation time, biodistribution and antitumor activity after intravenous injection in murine B16F10 melanoma tumor-bearing mice. The heparin-conjugated liposomes (heparin-liposomes) were prepared by fixation of the negatively charged heparin to the positively charged liposomes. The existence of heparin on the liposomal surface was confirmed by measuring the changes in the particle size, zeta potential and heparin amount of the liposomes. The stability of the heparin-liposomes in serum was higher than that of the control liposomes, due to the heparin-liposomes being better protected from the adsorption of serum proteins. The DOX-loaded heparin-liposomes showed high drug levels for up to 64 h after the intravenous injection and the half-life of DOX was approximately 8.4- or 1.5-fold higher than that of the control liposomes or polyethyleneglycol-fixed liposomes (PEG-liposomes), respectively. The heparin-liposomes accumulated to a greater extent in the tumor than the control or PEG-liposomes as a result of their lower uptake by the reticuloendothelial system cells in the liver and spleen. In addition, the DOX-loaded heparin-liposomes retarded the growth of the tumor effectively compared with the control or PEG-liposomes. These results indicate the promising potential of heparin-liposomes as a new sterically stabilized liposomal delivery system for the enhancement of the therapeutic efficacy of chemotherapeutic agents.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Han HD,Lee A,Song CK,Hwang T,Seong H,Lee CO,Shin BC

doi

10.1016/j.ijpharm.2006.02.007

keywords:

subject

Has Abstract

pub_date

2006-04-26 00:00:00

pages

181-8

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(06)00131-1

journal_volume

313

pub_type

杂志文章

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