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In vivo stability of ester- and ether-linked phospholipid-containing liposomes as measured by perturbed angular correlation spectroscopy

Derksen, Johannes T. P. and Baldeschwieler, John D. and Scherphof, Gerrit L. (1988) In vivo stability of ester- and ether-linked phospholipid-containing liposomes as measured by perturbed angular correlation spectroscopy. Proceedings of the National Academy of Sciences of the United States of America, 85 (24). pp. 9768-9772. ISSN 0027-8424. PMCID PMC282862. doi:10.1073/pnas.85.24.9768.

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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 (111)In complexed to nitrilotriacetic acid, were injected intravenously in rats. Recovery of (111)In-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 ([G22(∞)] of the (111)In 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.

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Additional Information:© 1988 by the National Academy of Sciences. Contributed by John D. Baldeschwieler, September 6, 1988. We thank Dr. S. M. Sullivan for critically reading the manuscript and Dr. T. M. Handel for helpful suggestions and assistance with the animal experiments. J.T.P.D.'s stay at California Institute of Technology was made possible by North Atlantic Treaty Organization Grant 040506 85. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Funding AgencyGrant Number
North Atlantic Treaty Organization (NATO)040506 85
Issue or Number:24
PubMed Central ID:PMC282862
Record Number:CaltechAUTHORS:DERpnas88
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1054
Deposited By: Tony Diaz
Deposited On:15 Dec 2005
Last Modified:08 Nov 2021 19:07

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