Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude

Amphiphilic chitosan-based polymers (M-w < 20 kDa) self-assemble in aqueous media at low micromolar concentrations to give previously unknown micellar clusters of 100-300 nm in size. Micellar clusters comprise smaller 10-30 nm aggregates, and the nanopolarity/drug incorporation efficiency of their hydrophobic domains can be tailored by varying the degree of lipidic derivatization and molecular weight of the carbohydrate. The extent of drug incorporation by these novel micellar clusters is 1 order of magnitude higher than is seen with triblock copolymers, with molar polymer/drug ratios of 1:48 to 1:67. On intravenous injection, the pharmacodynamic activity of a carbohydrate propofol formulation is increased by 1 order of magnitude when compared to a commercial emulsion formulation, and on topical ocular application of a carbohydrate prednisolone formulation, initial drug aqueous humor levels are similar to those found with a 10-fold dose of prednisolone suspension.

Analysis of chain and blood group type and branching pattern of sialylated oligosaccharides by negative ion electrospray tandem mass spectrometry

We previously reported sequence determination of neutral oligosaccharides by negative ion electrospray tandem mass spectrometry on a quadrupole-orthogonal time-of-flight instrument with high sensitivity and without the need of derivatization. In the present report, we extend our strategies to sialylated oligosaccharides for analysis of chain and blood group types together with branching patterns. A main feature in the negative ion mass spectrometry approach is the unique double glycosidic cleavage induced by 3-glycosidic substitution, producing characteristic D-type fragments which can be used to distinguish the type 1 and type 2 chains, the blood group related Lewis determinants, 3,6-disubstituted core branching patterns, and to assign the structural details of each of the branches. Twenty mono- and disialylated linear and branched oligosaccharides were used for the investigation, and the sensitivity achieved is in the femtomole range. To demonstrate the efficacy of the strategy, we have determined a novel complex disialylated and monofucosylated tridecasaccharide that is based on the lacto-N-decaose core. The structure and sequence assignment was corroborated by :methylation analysis and H-1 NMR spectroscopy.

A study of the ethene-ozone reaction with photoelectron spectroscopy: measurement of product branching ratios and atmospheric implications

The ozone-ethene reaction has been investigated at low pressure in a flow-tube interfaced to a u.v. photoelectron spectrometer. Photoelectron spectra recorded as a function of reaction time have been used to estimate partial pressures of the reagents and products, using photoionization cross-sections for selected photoelectron bands of the reagents and products, which have been measured separately. Product yields compare favourably with results of other studies, and the production of oxygen and acetaldehyde have been measured as a function of time for the first time. A reaction scheme developed for the ozone-ethene reaction has been used to simulate the reagents and products as a function of time. The results obtained are in good agreement with the experimental measurements. For each of the observed products, the simulations allow the main reaction (or reactions) for production of that product to be established. The product yields have been used in a global model to estimate their global annual emissions in the atmosphere. Of particular interest are the calculated global annual emissions of formaldehyde (0.96 ± 0.10 Tg) and formic acid, (0.05 ± 0.01 Tg) which are estimated as 0.04% and 0.7% of the total annual emission respectively.