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Prolongation of residence time of liposome by surface-modification with mixture of hydrophilic polymers.

Abstract：

:The objective of this study is to evaluate the biodistribution characteristics of liposomes surface-modified with the mixture of polyethylene glycol (PEG) and polyvinyl alcohol (PVA) as a drug carrier for passive targeting of drugs. The liposomes (egg phosphatidylcholine:cholesterol=55:40, molar ratio) modified with both PEG and PVA (4:1 molar ratio) (PEG4%/PVA1% liposome) provided the largest AUC, which could be attributed to the smallest hepatic clearance of the liposomes. The liver perfusion studies clearly indicated that lower hepatic disposition of PEG4%/PVA1% liposome was ascribed to the decrease in its hepatic uptake via receptor-mediated endocytosis. Furthermore, the amounts of whole serum proteins and of opsonins such as complement C3 and immunoglobulin G adsorbed on PEG4%/PVA1% liposome were significantly smaller than those on the liposome solely modified with PEG (PEG5% liposome). On the other hand, several proteins were adsorbed at larger amount on PEG4%/PVA1% liposome than PEG5% liposome, and the protein identification by LC-MS/MS suggested that some of those proteins including albumin might function as dysopsonins. The decrease in the adsorbed amount of several opsonins and the increase in the adsorbed dysopsonins would be responsible for its lower affinity to the liver and long residence in the systemic circulation of PEG4%/PVA1% liposome.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Shehata T,Ogawara K,Higaki K,Kimura T

doi

10.1016/j.ijpharm.2008.04.004

subject

Has Abstract

pub_date

2008-07-09 00:00:00

pages

272-9

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(08)00278-0

journal_volume

359

pub_type

杂志文章

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