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Metabolic fate of [14C]triglyceride-entrapped lactosylceramide-bearing liposomes after intravenous injection into mouse.

Abstract：

:We investigated the distribution and fate of liposomes after their intravenous injection into a mouse. Liposomes were composed of dimyristoylphosphatidylcholine, cholesterol and dicetylphosphate (7:2:1, molar ratio) with or without lactosylceramide. They were characterized as small unilamellar vesicles, approximately 100 nm in diameter, using gel-exclusion chromatography on a Sephacryl S-1000, freeze-fracture electron microscope and dynamic light scattering method. Liposomes were very stable in serum as seen by the results of leakage of the entrapped marker and electrophoresis experiments. We demonstrated that liposomes were internalized by way of an endocytotic process via coated vesicles detected in the electron microscope. The increase in liver uptake of lactosylceramide-bearing liposomes was mostly accounted for by enhanced uptake in the parenchymal cells, while uptake by non-parenchymal cells was only slightly increased. This observation supported the notion that a galactose-specific receptor was involved in liver uptake of lactosylceramide liposomes. The lactosylceramide-bearing liposomes were preferentially recovered in the liver and were found to first be predominantly localized in the mitochondria-lysosomal fraction. They were then decomposed by lysosomal enzymes, and the hydrolyzed components were reincorporated into membrane phospholipids in the microsomal fraction. At the same time, a rapid and reversible exchange of phosphatidylcholine between microsomes and mitochondria was demonstrated.

journal_name

Chem Pharm Bull (Tokyo)

journal_title

Chemical & pharmaceutical bulletin

authors

Yoshioka S,Banno Y,Okano Y,Ohki K,Mizukami Y

doi

10.1248/cpb.40.1016

subject

Has Abstract

pub_date

1992-04-01 00:00:00

pages

1016-21

issue

4

eissn

0009-2363

issn

1347-5223

journal_volume

40

pub_type

杂志文章

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