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

Sphingolipids have been synthesized that contain as polar headgroups, model drugs ester-linked to the primary hydroxyl group of the ceramide core. The se lipids, when allowed to self assemble below their chain-melting temperat ures, either as single molecular species or in combination with other sphin golipid-derived amphiphiles, are shown to form supramolecular assemblies of varying morphologies including complex high axial ratio microstructures (C HARMs). 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 ce ramide of the core. These microstructures, which have exceptionally high su rface area display of attached headgroups, may be useful for controlled rel ease of pharmacological agents. (C) 2001 Published by Elsevier Science B.V.