In vivo Stability of Ester- and Ether-Linked Phospholipid-Containing Liposomes as Measured by Perturbed Angular Correlation Spectroscopy

To evaluate liposome formulations for use as intracellular sustained-release drug depots, we have compared the uptake and degradation in rat liver and spleen of liposomes of various compositions, containing as their bulk phospholipid an ether-linked phospholipid or one of several ester-linked phosph...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1988-12, Vol.85 (24), p.9768-9772
Main Authors: Derksen, Johannes T., Baldeschwieler, John D., Scherphof, Gerrit L.
Format: Article
Language:English
Subjects:
1,2-Dipalmitoylphosphatidylcholine
Animals
Biological and medical sciences
Blood
Body weight
Cholesterols
Delayed-Action Preparations
Eggs
General pharmacology
Lipids
Liposomes
Liposomes - pharmacokinetics
Liver
Liver - metabolism
Male
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Phosphatidylethanolamines
Phospholipid Ethers
Phospholipids
Radioactive decay
Rats
Rats, Inbred Strains
Spectrophotometry - methods
Sphingomyelins
Spleen
Spleen - metabolism
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Summary:To evaluate liposome formulations for use as intracellular sustained-release drug depots, we have compared the uptake and degradation in rat liver and spleen of liposomes of various compositions, containing as their bulk phospholipid an ether-linked phospholipid or one of several ester-linked phospholipids, by perturbed angular correlation spectroscopy. Multilamellar and small unilamellar vesicles (MLVs and SUVs), composed of egg phosphatidylcholine, sphingomyelin, distearoyl phosphatidylcholine (DSPC), dipalmitoyl phosphatidylcholine (DPPC) or its analog dihexadecylglycerophosphorylcholine (DHPC), and cholesterol plus phosphatidylserine, and containing 111In complexed to nitrilotriacetic acid, were injected intravenously in rats. Recovery of 111In-labeled liposomes in blood, liver, and spleen was assessed at specific time points after injection and the percentage of liposomes still intact in liver and spleen was determined by measurement of the time-integrated angular perturbation factor 111In of the [G22(∞ )] label. We found that MLVs but not SUVs, having DHPC as their bulk phospholipid, showed an increased resistance against lysosomal degradation as compared to other phospholipid-containing liposomes. The use of diacyl phospholipids with a high gel/liquid-crystalline phase-transition temperature, such as DPPC and DSPC, also retarded degradation of MLV, but not of SUV in the dose range tested, while the rate of uptake of these liposomes by the liver was lower.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.85.24.9768