Disposition of 3H-cholesteryl ether labeled liposomes following intravenous administration to mice: comparison with an encapsulated 14C-inulin as aqueous phase marker.

Abstract:

:In this study, the blood clearance and organ distribution of intravenously administered liposomes (distearoyl phosphatidylcholine [DSPC] and cholesterol in a ratio of 3:1) was evaluated by utilizing 3H-cholesteryl ether as the lipid phase marker. Also, the ability of liposomes, as a drug delivery system, to alter the distribution and retention of encapsulated agents was investigated by comparing the distribution of intravenously administered free and liposome-encapsulated 14C-inulin within a 48-hr postadministration period. Intravenously administered DSPC liposomes were distributed in all organs examined with the highest levels of 3H-cholesteryl ether and 14C-inulin present in the liver and spleen; peak levels occurred 3 hr postadministration (71.86% +/- 9.39 versus 77.67% +/- 10.30, respectively, in the liver and 5.05% +/- 1.07 versus 5.36% +/- 1.09, respectively, in the spleen) declining gradually during the remaining experimental period. The lowest levels of 3H-cholesteryl ether and 14C-inulin following administration of liposome-encapsulated inulin were found in the lung, kidney, and heart. The area under curve showed much more accumulation of 14C-inulin (6-fold higher) in the body following administration of the liposome-encapsulated drug than the free drug. The ratio of 3H to 14C following administration of liposome-encapsulated inulin was constant throughout the entire observation period, suggesting that the disposition of inulin acquired both the carrier's rate of clearance and tissue distribution. These results indicated that following intravenous administration of liposome-encapsulated inulin, the majority of the radioactively labeled formulation was retained by the organs of the reticuloendothelial system (liver and spleen); liposomes greatly enhanced the retention of inulin in the body; and the liposomal formulation did not destabilize and subsequently did not release the encapsulated inulin to the tissues and organs.

journal_name

Drug Deliv

journal_title

Drug delivery

authors

Anderson M,Paradis C,Omri A

doi

10.1080/713840396

keywords:

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

193-200

issue

3

eissn

1071-7544

issn

1521-0464

pii

964FQ4UWC1MR6YK8

journal_volume

10

pub_type

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