Endothelial, renal and hepatic variables in Wistar rats treated with Vancomycin.

Vancomycin (VCM) is indicated in combat against Gram-positive infections, but it is not considered a first-choice drug because of its adverse effects. It is believed that oxidative stress is the primary mechanism of endothelial injury and the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity. Moreover, dose recommendations, dilution, rates and types of infusion are still controversial. The aim of this study was to determine the effect of different VCM dilutions in endothelial, liver and kidney injuries by biochemical parameters and histopathological analysis. Wistar rats were randomly divided into six groups and subjected to femoral vein cannulation for drug administration. Control groups received 0.9 ml of saline and the others received VCM (10mg/Kg/day) at dilutions of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT, urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This study showed alterations in ALT which featured hepatotoxicity. However, drug dilutions were not able to show changes in other biochemical parameters. In contrast, kidney and endothelium pathological changes were observed. More studies are needed to characterize VCM induced kidney and endothelium toxicity and biochemical markers able to show such morphological modifications.

Development and evaluation of naproxen-loaded sericin/alginate beads for delayed and extended drug release using different covalent crosslinking agents.

Different polymer matrix compositions based on sericin and alginate blend (using or not the covalent crosslinking agents dibasic sodium phosphate, polyvinyl alcohol and polyethylene glycol) were evaluated to entrap naproxen. Sericin has been shown to be essential for improving incorporation efficiency. Comparing the formulations with and without crosslinking agent, the best results were obtained for that composed only of sericin and alginate, with satisfactory values of entrapment efficiency (>80%) and drug loading capacity (>20%). In this case, delayed release (<10% in acid medium) and prolonged release (~360 min) were achieved, with a complex release mechanism involving swelling and polymer chain relaxation. The incorporation of the drug could be confirmed by the techniques of characterization of X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), as well as drug compatibility with the polymer matrix. In addition, particles of suitable size for multiparticulate systems were obtained and with higher thermal stability when compared to the pure drug.

Mechanochemistry applied to reformulation and scale-up production of Ethionamide: Salt selection and solubility enhancement.

Ethionamide (ETH), a Biopharmaceutics Classification System class II drug, is a second-line drug manufactured as an oral dosage form by Pfizer to treat tuberculosis. Since its discovery in 1956, only one reformulation was proposed in 2005 as part of the efforts to improve its solubility. Due to the limited scientific research on active pharmaceutical ingredients (APIs) for the treatment of neglected diseases, we focused on the development of an approachable and green supramolecular synthesis protocol for the production of novel solid forms of ETH. Initially, three salts were crystal engineered and supramolecular synthesized via slow evaporation of the solvent: a saccharinate, a maleate and an oxalate. The crystal structures of all salts were determined by single crystal X-ray diffraction. In sequence, mechanochemical protocols for them were developed, being the scale-up production of the maleate salt successfully reproducible and confirmed by powder X-ray diffraction. Finally, a more complete solid-state characterization was carried out for the ETH maleate salt, including thermal analysis, infrared spectroscopy, scanning electron microscopy and equilibrium solubility at different dissolution media. Although ETH maleate is thermodynamically less stable than ETH, the equilibrium solubility results revealed that this novel salt is much more soluble in purified water than ETH, thus being a suitable new candidate for future formulations.

Antioxidant and cytotoxic effects of crude extract, fractions and 4-nerolidylcathecol from aerial parts of Pothomorphe umbellata L. (Piperaceae).

The crude ethanolic extract from aerial parts of Pothomorphe umbellata L. (Piperaceae) and fractions obtained by partitions sequentially among water-methanol, methylene chloride, and ethyl acetate, as well as the major constituent, 4-nerolidylcatechol, were, respectively, evaluated and evidenced for antioxidant and cytotoxic effects through fluorometric microplate and microculture tetrazolium assays in HL-60 cells. The crude ethanolic extract demonstrated the preeminent antioxidant activity (IC50 = 1.2 µg/mL) against exogenous cytoplasmic reactive oxygen species, followed by the water-methanolic (IC50 = 4.5 µg/mL), methylene chloride (IC50 = 5.9 µg/mL), ethyl acetate (IC50 = 8.0 µg/mL), 4-nerolidylcatechol (IC50 = 8.6 µg/mL), and the sterol fractions (IC50 > 12.5 µg/mL). Vitamin C, the positive control used in this assay, presented IC50 value equivalent to 1.7 µg/mL. 4-Nerolidylcatechol (IC50 = 0.4 µg/mL) and methylene chloride fraction (IC50 = 2.3 µg/mL) presented considerable cytotoxicity probably because of the presence of an o-quinone, an auto-oxidation by product of the catechol. Polar compounds, present in the ethanol extract, appear to increase the solubility and stability of the major active constituent, acting synergistically with 4-nerolidylcatechol, improving its pharmacokinetic parameters and increasing significantly its antioxidant activity which, in turn, suggests that the aqueous-ethanolic extract, used in folklore medicine, is safe and effective.