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Continuous and highly variable rate controlled release of model drugs from sphingolipid-based complex high axial ratio microstructures.

Authors
  • Goldstein, A S
  • Gelb, M H
  • Yager, P
Type
Published Article
Journal
Journal of Controlled Release
Publisher
Elsevier
Publication Date
Jan 29, 2001
Volume
70
Issue
1-2
Pages
125–138
Identifiers
PMID: 11166413
Source
Medline
License
Unknown

Abstract

Sphingolipids have been synthesized that contain as polar headgroups, model drugs ester-linked to the primary hydroxyl group of the ceramide core. These lipids, when allowed to self assemble below their chain-melting temperatures, either as single molecular species or in combination with other sphingolipid-derived amphiphiles, are shown to form supramolecular assemblies of varying morphologies including complex high axial ratio microstructures (CHARMs). Within these microstructures, the lipid esters are highly resistant to hydrolysis as compared to the esters dispersed as solitary monomers in aqueous solution or in a matrix of fluid phosphatidylcholine vesicles. The rate of headgroup hydrolysis within CHARMs may be manipulated over a broad range (days to years) by varying the length of the amide-linked fatty acyl chain in the ceramide core or the distance between the ester and the C-1 ceramide of the core. These microstructures, which have exceptionally high surface area display of attached headgroups, may be useful for controlled release of pharmacological agents.

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