FORMATION OF HIGH-AXIAL-RATIO-MICROSTRUCTURES FROM NATURAL AND SYNTHETIC SPHINGOLIPIDS

Amphiphiles that form high-axial-ratio-microstructures (HARMs) are bei ng considered as novel materials for controlled release of drugs and o ther biologically functional molecules. HARMs consisting of tubules, r ibbons, solid rods and helices are formed from sphingolipids by additi on of water to a solution of amphiphile in DMF. Single molecular speci es of galactocerebroside (GalCer) containing long unsaturated fatty ac id chains or natural GalCer containing mixed-length, non-hydroxy fatty acids (NFA-GalCer) or alpha-hydroxy fatty acids (HFA-GalCer) form cyl indrical structures. In contrast, single molecular species of GalCer c ontaining long saturated fatty acids form ribbons and helices. GalCer HARMs are typically under 100 nm in diameter and have lengths of sever al microns. The importance of the amide of GalCer for HARM formation w as evaluated using psychosine, which forms solid fibers, whereas sphin gosine and an analog of GalCer in which the amide is reduced to a seco ndary amine form amorphous aggregates. Single molecular species of cer amide containing long unsaturated fatty acid chains form cylindrical s tructures, whereas those with long saturated fatty acids form ribbons and helices. Short chain saturated ceramide also forms cylindrical str uctures. GalCer analogs with N-acetyl-glycine in place of the galactos e form fibers whereas those with N-acetyl-proline yield amorphous mate rial. The N-acetyl-proline-containing amphiphile can de doped into pur e GalCer or NFA-GalCer without perturbing tubule formation. (C) 1997 E lsevier Science Ireland Ltd.