Acyclovir delivery matrices based on poly(ethylene glycol)/chitosan semi-interpenetrating networks.

Chitosan matrix systems have been studied as potential vehicles for the prolonged release of acyclovir (ACV). The influence of chitosan concentration (from 0.83% to 1.67%) on viscoelastic properties of formulations with and without glyoxal was analyzed. For chitosan-poly(ethylene glycol) 400 formulations loss modulus (G'') are greater than storage modulus (G'). This corresponds to the characteristic behavior of nonstructured systems. When glyoxal was added to the chitosan-poly(ethylene glycol) 400 formulations, gelled matrix was obtained (i.e., G' is higher than G''), except for the lowest chitosan concentration. ACV release rates for the both types of systems, with and without glyoxal, were also determined. The ACV diffusion coefficient values from matrices are less than for the respective formulation without glyoxal and it was found to depend on the crosslink density within the matrices. Viscoelastic parameters, dynamic moduli (G', G''), and complex viscosity (eta*), were correlated with the ACV diffusion coefficients (D). The complex viscosity (eta*) could be used as a parameter of predictive value for the release rate of drugs.

Analysis of the potential carcinogenicity of coffee and its related compounds in a medium-term liver bioassay of rats.

The potential carcinogenicity of coffee and related compounds was examined using a medium-term liver bioassay based on the induction of glutathione S-transferase placental form (GST-P)-positive foci in F344 rats. A total of 230 males were initially injected with diethylnitrosamine (200 mg/kg body weight, ip) or saline as controls and 2 wk later were fed on diet or drinking water supplemented as follows for 6 wk: 5% regular instant coffee; 5% decaffeinated instant coffee; freshly brewed coffee, 8 g in 140 ml water; 0.1% caffeine, 0.2% methylglyoxal, 0.2% glyoxal; or 0.3% theophylline in the drinking water (w/v); and 0.4% theobromine in the diet (w/w). All rats were subjected to two-thirds partial hepatectomy at wk 3 and killed at wk 8. The resultant values for GST-P-positive hepatic focus induction were slightly increased with methylglyoxal and decreased with glyoxal and theobromine compared with the corresponding controls. Although the increase in number of foci for methylglyoxal was statistically significant at P < 0.05, the value was within the historical control levels. Regular and decaffeinated instant coffee as well as fresh-brewed coffee, caffeine and theophylline exerted no effects on focus development. Thus, the coffee-related compounds examined demonstrated no obvious enhancing potential, and it is therefore concluded that coffee and its main constituents are not carcinogenic for the rat liver.