beta-Conglycinin (7S) and glycinin (11S) exert a hypocholesterolemic effect comparable to that of fenofibrate in rats fed a high-cholesterol diet

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution

Praziquantel has been shown to be highly effective against all known species of Schistosoma infecting humans. Spherical nanoparticulate drug carriers made of poly(D,L-lactide-co-glycolide) acid with controlled size were designed. Praziquantel, a hydrophobic molecule, was entrapped into the nanoparticles with theoretical loading varying from 10 to 30% (w/w). This investigates the effects of some process variables on the size distribution of nanoparticles prepared by emulsion-solvent evaporation method. The results show that sonication time, PLGA and drug amounts, PVA concentration, ratio between aqueous and organic phases, and the method of solvent evaporation have a significant influence on size distribution of the nanoparticles. (C) 2004 Elsevier B.V. All rights reserved.

Improvement of antischistosomal activity of praziquantel by incorporation into phosphatidylcholine-containing liposomes

Praziquantel (PZQ) is effective against all known species of Schistosomes that infect humans. The failure of mass treatment of schistosomiasis has been attributed to the fact that therapy is not sufficiently long-lasting. This effect may be due to the low bioavailability of PZQ that has a low hydrosolubility and fast metabolism. Liposomes have been used to prolong drug levels. reduce the side effects, direct drugs to specific sites and increase bioavailability after administration. The aim of this work was to study the effect of phosphatidylcholine (PC)-containing liposomes to vehiculate PZQ to improve the treatment of schistosomiasis. The in vitro Study was carried out using Schistosoma mansoni parasites recovered by perfusion from the hepatic portal system of infected mice. Suspensions of liposomes with PZQ and free PZQ were administered p.o. in mice after 14 days of infection. The effect of both preparations in vitro on S. mansoni culture was similar. In the in vivo test, PZQ-liposomes caused a decrease in amounts of eggs and parasites. Liposomes improve the antischistosomal activity of praziquantel. This can be used as a starting point to investigate alternative administration routes or dosage forms and to examine the mechanism of intestinal absorption of PRZ © 2005 Elsevier B.V. All rights reserved.

The effect of pyrazinamide and rifampicin on isoniazid metabolism in rats

Hepatotoxicity is the main concern during tuberculosis chemotherapy with the first-line drugs isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR). Since these hepatotoxic events have been associated with INH metabolites, the study aimed to measure the area under curve (AUC) parameter for INH and its metabolites acetylisoniazid (AcINH), hydrazine (Hz) and acetylhydrazine (AcHz), when groups of rats were pre-treated for 21 days with INH alone or in combination with RMP and/or PYR, in the following amounts per kg body weight: INH 100 mg; INH 100 mg + RMP 100 mg; INH 100 mg + PYR 350 mg; INH 100 mg + PYR 350 mg + RMP 100 mg. It was found that co-administration of RMP, PYR and RMP + PYR caused a significant decrease in the AUC for INH. Co-administration of PYR was the only treatment that caused a significant increase in the AUC for Hz and a decrease in the AUC for its acetylated product AcHz. The AUC for AcINH was not significantly altered in any experimental group. In conclusion, the increased metabolism of INH in all the drug combinations and the significantly higher production of Hz in the group INH + PYR might be linked with exacerbated hepatotoxic effects of these drug associations. Copyright (c) 2007 John Wiley & Sons, Ltd.

The effect of rifampicin and pyrazinamide on isoniazid pharmacokinetics in rats

Tuberculosis chemotherapy involves combination of the drugs isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR) for a 6-month period. The present work investigated the influence of RMP and PYR on the pharmacokinetic parameters of INH when groups of rats were pre-treated for 21 days with INH alone or in combination with RMP and/or PYR, in the following amounts per kg body weight: INH 100 mg; INH 100 mg + RMP 100 mg; INH 100 mg + PYR 350 mg; INH 100 mg + PYR 350 mg + RMP 100 mg. It was found that the co-administration of PYR caused an increase in the INH distribution volume (V-d/F), half-life of elimination t(1)/2(beta)) and clearance (Cl-T/F), and a decrease in the area under curve 0 to 24 h (AUC). Co-administration of RMP caused an increase in the Cl-T/F and a decrease in the AUC. The combination INH + PYR + RMP caused an increase in the Cl-T/F and a decrease in the AUC. These significant pharmacokinetic interactions between the tuberculostatic drugs might be related to differences in the therapeutic and toxic effects. Copyright 0( 2007 John Wiley & Sons, Ltd.

Piroxicam encapsulated in liposomes: Characterization and in vivo evaluation of topical anti-inflammatory effect

Liposomes of soya phosphatidylcholine, cholesterol, and stearylamine (molar ratio 6/3/1) and 0.1% alpha-tocopherol were prepared by the extrusion of multilamellar vesicles through 0.2-mu m polycarbonate membrane. Liposomes were characterized by electron transmission microscopy, and the mean structure diameter was 278 nm. The encapsulation efficiency obtained was 12.73%. The topical anti-inflammatory effect was evaluated in vivo by the cotton pellet granuloma method. We analyzed free piroxicam at 4 mg/kg, piroxicam encapsulated in liposomes added to 1.5% hydroxyethylcellulose (HEC) gel at 1.6 mg/kg, and piroxicam encapsulated in liposomes added to HEC gel at 4 mg/kg; the inhibition of inflammation obtained was 21.1%, 32.8%, and 47.4%, respectively. These results showed that the encapsulation of piroxicam produced an increase of topical anti-inflammatory effect, suggesting that the inhibition of inflammation can be obtained with lower drug concentrations.

Nanotechnology-based Drug Delivery Systems for Dermatomycosis Treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structure and viscoelastic behavior of pharmaceutical biocompatible anionic microemulsions containing the antitumoral drug compound doxorubicin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of cationic micelles on the decomposition of alpha-aminophenyl cephalosporins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Darunavir: A Critical Review of Its Properties, Use and Drug Interactions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of cocaine on periadolescent rats with or without early maternal separation

Cocaine-induced behavioral sensitization and weight loss were investigated in periadolescent Wistar rats kept with their mothers or subjected to repeated maternal separation. Litters allocated to the separation procedure were placed in a temperature-controlled (33ºC) chamber for 3 h per day from postnatal day 6 (P6) to P20. Non-handled rats were left undisturbed until weaning. Treatments were started on P30-31 and the test was performed on P36-37. Animals received injections of saline or cocaine (10 mg/kg, sc) twice daily for 5 days. on day 6 all animals received saline. on day 7 animals were challenged with 10 mg/kg cocaine and their locomotion was evaluated in activity cages. A third group received saline throughout the 7-day period. Body weights were recorded on P30-31 and P36-37. Two-way ANOVA on body weights showed a main effect of treatment group (F(1,35) = 10.446, P = 0.003; N = 10-12). Non-handled rats treated with cocaine for 5 days gained significantly less weight, while no significant effect was observed in maternally separated rats. Two-way ANOVA revealed a main effect of drug treatment on locomotor activity (F(2,32) = 15.209, P<0.001; N = 6-8), but not on rearing condition (F(1,32)<0.001, P = 0.998). Animals pretreated with cocaine showed a clear behavioral sensitization relative to the saline group. No difference in the magnitude of sensitization was found between separated and non-handled animals. Only the effect of cocaine on weight gain was significantly affected by repeated episodes of early maternal separation during the pre-weaning period.

4-Fluoro-2-methoxyphenol, an apocynin analog with enhanced inhibitory effect on leukocyte oxidant production and phagocytosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of a nanostructured dendrimer-naloxonazine complex on endogenous opioid peptides mu(1) receptor-mediated post-ictal antinociception

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The self-polarization effect in Pb(Zr0.50Ti0.50)O-3 thin films with no preferential orientation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Artemisia annua L. leaves essential oil and ethanol extract on behavioral assays

Artemisia annua tem sido utilizada tradicionalmente para o tratamento de malária e febre na China devido à presença do princípio ativo, artemisinina. O presente trabalho avaliou a atividade central de do óleo essencial obtido por hidrodestilação e do extrato etanólico bruto de folhas frescas de A. annua em modelo in vivo como parte de um screening farmacológico dessa espécie. Sono induzido por pentobarbital, nado forçado e o ensaio de campo aberto são modelos de estudo conhecidos para o estudo de fármacos sobre depressão induzida. A administração do óleo essencial ou extrato bruto etanólico de A. annua aumentaram o tempo de imobilidade no teste do nado forçado. Por outro lado, diminuíram outros parâmetros no campo aberto, como ambulação, exploração, o ato de lamber as patas ou se lamber. Ambos produtos aumentaram o tempo de sono induzido por pentobarbital, com o óleo essencial apresentando um efeito superior ao do extrato. Pela análise dos resultados, é possível sugerir que tanto o extrato bem como o óleo essencial podem atuar como depressores do Sistema Nervoso Central (SNC).