Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of

Elevated Iron Chelating Activity of Ilex paraguariensis Leaf Infusion: in vitro and in vivo Pilot Studies

Abstract This study presents an Ilex paraguariensis leaf infusion with important potential as natural iron-chelating. The impact of infusion time and the water volume to obtain an Ilex paraguariensis leaf infusion with high phenolic content and iron chelating activity, such as the stability of these proprieties in the storage time and temperature (immediately and after 24 h at 8 and 25 (C) were assessed. The acute consumption effect of this infusion to reduce iron absorption in vivo was also evaluated. A preliminary crossover trial with volunteers that ingested a meal containing non-haem iron (11.4 mg) with the treatments: Ilex paraguariensis leaf infusion with the highest phenolic content and iron chelating activity (200 mL) or control (200 mL water). Blood samples were withdrawn before and 1, 2, 3 and 4 h after the meal for serum iron measurement. The highest phenolic content (18.1 mg/mL) and iron chelating activity ((100%) were observed for 10 min infusion time using 30 g leaves/300 mL water. Storage at 8 or 25 (C for 24 h decreased total phenolics and di-caffeoylquinic acids by 23.5% and 25.5%, respectively (p< 0.05), without affecting the iron-chelating activity due to a saturating chelating effect at 3.34 mg/mL phenolic content. Inhibition of the iron absorption in vivo by infusion was 78% considering the iron recovery at peak maximum. The in vitro and preliminary in vivo results showed a functional property of the Ilex paraguariensis leaf infusion that may be useful for adjuvant management of iron overload diseases.

Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment

BACKGROUND The current chemotherapy for Chagas disease is based on monopharmacology with low efficacy and drug tolerance. Polypharmacology is one of the strategies to overcome these limitations. OBJECTIVES Study the anti-Trypanosoma cruzi activity of associations of benznidazole (Bnz) with three new synthetic T. cruzi-triosephosphate isomerase inhibitors, 2, 3, and 4, in order to potentiate their actions. METHODS The in vitro effect of the drug combinations were determined constructing the corresponding isobolograms. In vivo activities were assessed using an acute murine model of Chagas disease evaluating parasitaemias, mortalities and IgG anti-T. cruzi antibodies. FINDINGS The effect of Bnz combined with each of these compounds, on the growth of epimastigotes, indicated an additive action or a synergic action, when combining it with 2 or 3, respectively, and an antagonic action when combining it with 4. In vivo studies, for the two chosen combinations, 2 or 3 plus one fifth equivalent of Bnz, showed that Bnz can also potentiate the in vivo therapeutic effects. For both combinations a decrease in the number of trypomastigote and lower levels of anti-T. cruzi IgG-antibodies were detected, as well clear protection against death. MAIN CONCLUSIONS These results suggest the studied combinations could be used in the treatment of Chagas disease.

In vitro and In vivo Antitrypanosomal Effects of Petroleum Ether, Chloroform and Methanol Extracts of Artemisia maritima Linn.

Petroleum ether, chloroform and methanol extracts of the whole plant of Artemisia maritima Linn were studied in vitro and in vivo for antitrypanosomal activity against Trypanosoma brucei brucei in Swiss albino mice. The extracts were also screened for phytochemicals/secondary metabolites. All the extracts showed trypanocidal activity against T. brucei brucei in vitro with the petroleum ether extract showing the highest activity. The in vivo study revealed that only the chloroform extract A. maritima exhibited antitrypanosomal activity. This extract at a dose of 100mg/kg body weight significantly (p<0.05) reduced the parasitemia in T. brucei brucei infected mice when compared with the other treatment groups. The chloroform extract of A. maritima at this dose reduced the level of parasitemia to 26%. This reduction in the level of parasitemia is statistically significant (p<0.05) compared to the other treatment groups and the untreated control group. The result of the phytochemical analysis revealed that the extracts contain secondary metabolites like flavonoids, terpenoids, steroids, anthraquinones and alkaloids. The presence of these secondary metabolites in this plant might be responsible for the antitrypanosomal activity exhibited by its extracts.

Histological and biochemical effects induced by sublethal doses of Bothrops jararacussu venom in mice

Snake venom is characterized by hemorrhagic, coagulant, proteolytic and myotoxic activities which in Bothrops jaracussu venom are related to intraspecific variations. In the present study, female Swiss mice were divided into two groups: treated with 25æg or 50æg venom. These were subdivided into three groups of six animals each, according to blood collection: 2, 4 or 24h after venom injection. Animals were anesthetized using diethyl-ether inhalation and 1ml of blood was collected by heart puncture. Then, the following organs were removed: spleen, skeletal muscle, kidneys, liver and lungs; histological sections were obtained and stained with hematoxylin-eosin (HE). The following biochemical parameters were analyzed: aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT), total lactate dehydrogenase (LDH), glucose, creatinine and urea levels, and total protein content. Results showed significant alterations in AST, LDH, glucose and urea levels, and total protein content, as well as important tissue alterations in the liver, kidneys and lungs. It could be concluded that, even using sublethal doses of venom, there were significant changes in almost all the tested biochemical parameters as well as tissue alterations in the kidneys and lungs.(AU)