Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain

Abstract Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi, whose treatment has remained unsatisfactory for over 50 years, given that it is limited to two drugs. Benznidazole (BZN) is an efficient antichagasic drug used as the first choice, although its poor water-solubility, irregular oral absorption, low efficacy in the chronic phase, and various associated adverse effects are limiting factors for treatment. Incorporating drugs with such characteristics into nanostructured lipid carriers (NLC) is a promising alternative to overcome these limiting obstacles, enhancing drug efficacy and bioavailability while reducing toxicity. Therefore, this study proposed NLC-BZN formulations in different compositions prepared by hot-melt homogenization followed by ultrasound, and the optimized formulation was characterized by FTIR, DRX, DSC, and thermogravimetry. Biological activities included in vitro membrane toxicity (red blood cells), fibroblast cell cytotoxicity, and trypanocidal activity against epimastigotes of the Colombian strain of T. cruzi. The optimized NLC-BZN had a small size (110 nm), negative zeta potential (-18.0 mV), and high encapsulation (1.64% of drug loading), as shown by infrared spectroscopy, X-ray diffraction, and thermal analysis. The NLC-BZN also promoted lower in vitro membrane toxicity (<3% hemolysis), and 50% cytotoxic concentration (CC50) for NLC-BZN in L929 fibroblast cells (110.7 µg/mL) was twice the value as the free BZN (51.3 µg/mL). Our findings showed that the NLC-BZN had higher trypanocidal activity than free BZN against the epimastigotes of the resistant Colombian strain, and this novel NLC-BZN formulation proved to be a promising tool in treating Chagas disease and considered suitable for oral and parenteral administration

Effect of propolis on mast cells in wound healing.

Wound healing is divided into three phases: inflammatory, proliferative and remodeling. Mast cells participate in all these phases. The aim of the present study was to determine the effects of propolis on the population of mast cells in oral surgical wounds in comparison to the results obtained with dexamethasone. This study was prospective, in vivo, randomized, semiexperimental, quantitative and comparative animal. A circular surgical wound was made on the dorsum of the tongue of 90 hamsters divided into three experimental groups: topical application of 30% propolis alcoholic extract (Group 1); 0.1% dexamethasone in orabase cream (Group 2); and orabase cream alone (Group 3). Applications were performed every 12 h throughout the experiment. The postoperative times for killing of the animals were 1, 3, 7, 14 and 28 days. The Student's t test for independent samples was employed in the statistical analysis. In the inflammatory phase of healing, propolis caused a greater reduction in the number of mast cells on the edge and in the central region of the surgical wound in comparison to dexamethasone. Moreover, the number of mast cells on day 1 was lower in the central region of the wounds treated with the orabase cream alone in comparison to dexamethasone. In conclusion, the anti-inflammatory action of propolis mediated by mast cells was more effective than dexamethasone in the inflammatory phase of healing.