Ethosomes - novel vesicular carriers for enhanced delivery: characterization and skin penetration properties.

This work describes a novel carrier for enhanced skin delivery, the ethosomal system, which is composed of phospholipid, ethanol and water. Ethosomal systems were much more efficient at delivering a fluorescent probe to the skin in terms of quantity and depth, than either liposomes or hydroalcoholic solution. The ethosomal system dramatically enhanced the skin permeation of minoxidil in vitro compared with either ethanolic or hydroethanolic solution or phospholipid ethanolic micellar solution of minoxidil. In addition, the transdermal delivery of testosterone from an ethosomal patch was greater both in vitro and in vivo than from commercially available patches. Skin permeation of ethosomal components, ethanol and phospholipid, was demonstrated in diffusion-cell experiments. Ethosomal systems composed of soy phosphatidylcholine 2%, ethanol 30% and water were shown by electron microscopy to contain multilamellar vesicles. 31P-NMR studies confirmed the bilayer configuration of the lipids. Calorimetry and fluorescence measurements suggested that the vesicular bilayers are flexible, having a relatively low T(m) and fluorescence anisotropy compared with liposomes obtained in the absence of ethanol. Dynamic light scattering measurements indicated that ethanol imparted a negative charge to the vesicles. The average vesicle size, as measured by dynamic light scattering, was modulated by altering the ethosome composition. Experiments using fluorescent probes and ultracentrifugation showed that the ethosomes had a high entrapment capacity for molecules of various lyophilicities.

Enantiomer resolution of nefopam hydrochloride, a novel analgesic: a study by liquid chromatography and circular dichroism spectroscopy.

Nefopam, a potent analgesic, has been completely resolved into enantiomers on a preparative scale by low-pressure liquid chromatography on swollen, microcrystalline triacetylcellulose. The enantiomerically pure hydrochlorides were prepared from the base, and the circular dichroism spectra of the free base and the hydrochloride are reported.

Increased affinity of choline acetyltransferase for choline in Alzheimer's disease: a steady-state kinetic study.

The steady-state kinetics of choline acetyltransferase (CAT) from autopsy samples of human caudate nucleus of aged controls and of patients with Alzheimer's disease was studied. In 10 samples from Alzheimer's disease-afflicted brains the affinity for the limiting substrate choline (Ch) was significantly higher: Michaelis constant KmCh was for these samples 1.93 +/- 0.72 mM while in the samples from 9 age-matched controls KmCh was 2.53 +/- 0.78 mM. The difference is statistically significant (P less than 0.05). Endogenous choline concentrations in the samples were 124 +/- 39 (n = 10) nmol/g wet wt. in the Alzheimer's disease-afflicted samples and 180 +/- 57 (n = 9) nmol/g wet weight (n = 9) in the control samples (P less than 0.05). The initial velocity at 70 microM acetyl co-enzyme (AcCoA) in Alzheimer's samples was 171.5 +/- 131.0 pmol [14C]acetyl choline [14C]ACh/mg protein/min as compared to the controls 422.1 +/- 231.0 pmol [14C]ACh/mg protein/min replicating many previous findings about decline of CAT activity in Alzheimer's disease. However, in the same samples the affinity for the other substrate acetyl-CoA (AcCoA) was significantly lower for the Alzheimer patients, KmAcCoA = 61 +/- 40 microM, than for the age-matched control patients, KmAcCoA = 28 +/- 8 microns (P less than 0.01). The data suggest some compensation of the loss of enzyme molecules via changed affinity for the limiting substrate, Ch.