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This study aimed to evaluate the in vivo anti-Leishmania amazonensis activity of a Phospholipase A2 (Asp49-PLA2), isolated from Bothrops jararacussu venom, encapsulated in liposomes as a modified toxin release system. The activity of the liposomes was evaluated in BALB/c mice, previously infected with 1×105 of the parasite's promastigotes. The size of the paw lesion in Asp49-PLA2-liposomal-treated animals, after 21days, was observed as decreasing by 16% relative to the untreated control group and 12% by the Glucantime®-treated animals, which was used as a reference drug. At the end of the treatment, the animals were sacrificed and the paw and lymph node tissues were collected. Part of the collection was used to recover amastigotes and another to quantify cytokines and nitrites. In the group treated with Asp49-PLA2-liposomes the parasitic load was observed to be reduced by 73.5% in the macerated lymph node, compared to the control group. Comparatively, in the paw tissue was observed a reduction of 57.1%. The infected groups treated with Asp49-PLA2-liposomes showed significant production in TNF-α measured in lymph nodes and paw (43.73pg/mL±2.25 and 81.03pg/mL±5.52, respectively) and nitrite levels (31.28µM±0.58 and 35.64µM±5.08) also measured in lymph nodes and paw tissues, respectively, compared to untreated groups. These results indicate that the Asp49-PLA2-loaded liposomes were able to activate the production of some cellular components of the protective TH1 response during the infection, constituting a promising tool for inducing the microbicidal activity of the Leishmania-infected macrophages.

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The determination of nimodipine in the presence of its degradation products, formed through photolysis, acidic and alkaline hydrolysis, and the drug degradation kinetics under these conditions, was investigated through a validated liquid chromatography method. Separation was achieved using a Phenomenex Luna C18 column (250 × 4.6 mm i.d., 5 µm) with a mobile phase consisting of acetonitrile-methanol-water (55:11:34, v/v/v), at 0.5 mL/min and with ultraviolet detection at 235 nm. The method was considered to be specific, accurate, precise, robust and linear over the concentration range of 5.0 to 35.0 µg/mL. The drug followed a first-order reaction for both hydrolysis and photolysis in methanol, and zero-order for photolysis in acetonitrile and water. The calculated activation energies were 10.899 and 23.442 kcal/mol for alkaline and acidic hydrolysis, respectively. No degradation was observed under thermal and oxidative stress conditions.

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An HPLC method was developed and validated for the simultaneous determination of buclizine, tryptophan, pyridoxine, and cyanocobalamin in pharmaceutical formulations. The chromatographic separation was carried out on an RP-C18 column using a mobile phase gradient of methanol, 0.015 M phosphate buffer (pH 3.0), and 0.03 M phosphoric acid at a flow rate of 1.0 mL/min and UV detection at 230, 280, and 360 nm, respectively, for buclizine, tryptophan, pyridoxine, and cyanocobalamin. The method validation yielded good results with respect to linearity (r>0.999), specificity, precision, accuracy, and robustness. The RSD values for intraday and interday precision were below 1.82 and 0.63%, respectively, and recoveries ranged from 98.11 to 101.95%. The method was successfully applied for the QC analysis of buclizine, tryptophan, pyridoxine, and cyanocobalamin in tablets and oral suspension.

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This paper describes the antioedematogenic profile of marrubiin (1), the main constituent of Marrubium vulgare, a medicinal plant used in folk medicine of several countries to treat different pathologies. Compound (1) was analyzed in a model of microvascular leakage in mice ears. The results show that it exhibits significant and dose-related antioedematogenic effects. The results obtained for ID50 values (mg/kg, i.p.) and maximal inhibition (%) for the different phlogistic agents used were as follows: histamine (HIS, 13.84 mg/kg and 73.7%); (BK, 18.82 mg/kg and 70.0%); carrageenan (CAR, 13.61 mg/kg and 63.0%). The other phlogistic agonists, such as prostaglandin E2 (PGE2), caused inhibition of less than 50%. In addition, (1) (100 mg/kg) significantly inhibited the OVO-induced allergic edema in actively sensitized animals (maximal inhibition 67.6+/-4%). Our results demonstrate that the systemic administration of marrubiin exerts a non-specific inhibitory effect on pro-inflammatory agent-induced microvascular extravasation of Evans blue in mouse ear.

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