Controlled release of glibenclamide from monolithic silica subdermal implants produced by the sol-gel process and its use for hyperglycaemia treatment in a murine model.

Glibenclamide is an anti-hyperglycaemic drug that is commonly used for the treatment of type 2 diabetes mellitus and has promising new medical indications. However, this drug is associated with high rates of serious hypoglycaemic episodes as a result of its pharmacological activity. Administering the drug through controlled release delivery systems could reduce the incidence of these episodes. In this study, glibenclamide silica monolithic xerogel implants for subdermal application (GMSIx) were developed using the sol-gel technique for matrix synthesis with TEOS with different drying conditions (environmental, 60, 90, and 120 °C, which were named as GMSIE, GMSI60, GMSI90, and GMSI120, respectively). The inclusion of the drug in monoliths was monitored by DSC, FTIR, and PXRD. The effect of drying conditions on the morphology, moisture content, hardness, dosage uniformity, surface characteristics, and drug release mechanism of glibenclamide from the matrices was systematically investigated. Oral Glucose Tolerance Tests were performed with mice to evaluate the efficacy of the GMSI in maintaining blood glucose levels. Glibenclamide was completely included in a non-crystalline solid form in the matrixes. The moisture content, hardness, dosage uniformity, and surface characteristics depend on the drying conditions. The monolithic matrices showed a mesoporous surface with high surface area, and a narrower pore size distribution occurred for GMSI60. GMSIE and GMSI60 showed non-Fickian anomalous Korsmeyer-Peppas glibenclamide release kinetics. GMSI90 and GMSI120 showed controlled release of the drug through dissolution. When GMSI60 was administered to mice, glucose blood levels were effectively maintained despite a high oral glucose load in the animals, showing a sustained effect of the drug released from this new sol-gel drug delivery system.

Increased acetylcholine esterase activity produced by the administration of an aqueous extract of the seed kernel of Thevetia peruviana and its role on acute and subchronic intoxication in mice.

BACKGROUND: The real mechanism for Thevetia peruviana poisoning remains unclear. Cholinergic activity is important for cardiac function regulation, however, the effect of T. peruviana on cholinergic activity is not well-known. OBJECTIVE: To study the effect of the acute administration of an aqueous extract of the seed kernel of T. peruviana on the acetylcholine esterase (AChE) activity in CD1 mice as well its implications in the sub-chronic toxicity of the extract. MATERIALS AND METHODS: A dose of 100 mg/kg of the extract was administered to CD1 mice and after 7 days, serum was obtained for ceruloplasmin (CP) quantitation and liver function tests. Another group of mice received a 50 mg/kg dose of the extract 3 times within 1 h time interval and AChE activity was determined for those animals. Heart tissue histological preparation was obtained from a group of mice that received a daily 50 mg/kg dose of the extract by a 30-days period. RESULTS: CP levels for the treated group were higher than those for the control group (Student's t-test, P ≤ 0.001). AChE activity in the treated group was significantly higher than the control group (Tukey test, control vs. T. peruviana, P ≤ 0.001). Heart tissue histological preparations showed leukocyte infiltrates and necrotic areas, consistent with infarcts. CONCLUSION: The increased levels of AChE and the hearth tissue infiltrative lesions induced by the aqueous seed kernel extract of T. peruviana explains in part the poisoning caused by this plant, which can be related to an inflammatory process.

The effect of the aqueous extract of Helietta parvifolia A. Gray (Rutaceae) stem bark on carrageenan-induced paw oedema and granuloma tissue formation in mice.

AIMS OF STUDY: Despite the ethnopharmacological relevance of Helietta parvifolia A. Gray (Rutaceae) in Mexico, we found no significant pharmacological studies of this plant in the scientific literature. The aim of the present study was to establish the anti-inflammatory effect of an aqueous extract of the stem bark of Helietta parvifolia in mice. MATERIALS AND METHODS: The anti-inflammatory activity of the aqueous extract of the stem bark of Helietta parvifolia was evaluated using carrageenan-induced paw oedema in mice, and the cotton pellet granuloma method. RESULTS: An extract dose ranging from 20 to 80 mg/kg p.o. showed a non-significant effect over the initial phase of carrageenan-induced oedema. However, it showed a significant inhibition of oedema after 3h, which can be related to the inhibition of the release of kinin-like substances. An ID(50) value of 47.4 mg/kg was obtained for the plant extract. The extract also suppressed granulomatous tissue formation during chronic inflammation. The inhibitory values were 19.2, and 22.2, corresponding to 40 and 80 mg/kg doses of extract respectively. CONCLUSIONS: Aqueous extract showed a statistically significant anti-inflammatory effect in mice during the late phase of acute inflammation and during chronic inflammation. However, the exact mechanism(s) of anti-inflammatory effects of Helietta parvifolia observed in this study remains unclear.

Comparación de las constantes fisiológicas sanguíneas de los ratones CD1, heterocigótico et/+ y desnudo et/et / Comparison of blood physiologic values from CD1, heterocygotic et/+ and naked et/et mice

En este estudio se analizaron los valores sanguíneos normales de una mutante de ratones desnudos conocidos como et/et, se compararon con ratones CD 1, cepa de la cual surgió y con los heterocigóticos et/+. Los conteos leucocitarios y diferenciales mostraron que las poblaciones de leucocitos totales, linfocitos, monocitos y eosinófilos fueron significativamente mayores en los ratones et/et que en los CD 1 (P < 0.05); en los ratones desnudos, 89 por ciento presentó hipersegmentación de neutrófilos, mientras que sólo 10 por ciento de los heterocigóticos lo manifestó y no se observó en los ratones CD 1. En la población de linfocitos T totales CD3+ y en los CD8+ resultaron superiores los valores de los ratones et/et a los CD 1 (P < 0.05) y sin diferencia respecto a los et/+. Los valores en el hematocrito fueron mayores en los ratones et/et respecto de los CD 1(P < 0.05). En la cuantificación de proteínas plasmáticas, los ratones et/et presentaron menor densidad que los ratones CD 1. La fracción alfaglobulina del suero mostró diferencias en los ratones et/et, donde los machos presentan una concentración significativamente mayor (P < 0.05) a las hembras (8.94 por ciento ñ 1.81 vs 3.49 por ciento ñ 0.69). En el estudio del número de células linfoides en bazo, se observaron diferencias significativas en los ratones et/et que presentaron 43 células/50 m l, contra 97.5 en los ratones CD 1, mientras que los et/+ presentaron un valor intermedio sin significancia estadística. Con el análisis de resultados se concluye que los ratones et/et presentan dentro de sus características genéticas, una leucocitosis circulante con linfocitosis, monocitosis, eosinofilia y una linfopenia en bazo, así como la hipersegmentación de neutrófilos; lo anterior probablemente esté asociado a la hipersecreción adrenal que han descrito otros autores en los ratones et/et.