A Metformin-Ferulic Acid Salt with Improved Biopharmaceutical Parameters.

Though ferulic acid presents great hypoglycemic potential, it possesses limited aqueous solubility, and low oral bioavailability. When associated with metformin, the first-choice drug in Type 2 diabetes treatment, FA demonstrates synergistic hypoglycemic effects, however, it also causes certain undesirable dose-related effects. This study aimed to develop a new ferulic acid - metformin multicomponent system, and incorporate it into a solid dosage form with improved biopharmaceutical parameters. A novel metformin: ferulate (1:1) salt (MFS) was produced, which was properly characterized using differing analytical techniques, including single crystal analysis. Also during the course of the study, a new polymorph of the metformin free base was observed. The MFS was obtained using solvent evaporation methods, which achieved high yields in reproducible process, as well as a 740-fold increase in ferulic acid aqueous solubility. The MFS tablets developed met quality control requirements for this dosage form, as well as revealing excellent performance in vitro dissolution tests, presenting dissolution efficiency values of 95.4 ± 0.5%. Additionally, physicochemical instability was not observed in a study at 40 °C for 3 months for both MFS powder and its tablet form. The MFS product developed is a promising candidate for further Type 2 diabetes clinical study.

TanP: A Multifunctional Anionic Peptide From Tityus stigmurus Scorpion Venom.

Anionic peptides of scorpions are molecules rich in aspartic and/or glutamic acid residues and correspond to a class of peptides without disulfide bonds that are still little explored. TanP is a linear anionic peptide (50 amino acid residues and net charge -20) present in the venom gland of the scorpion, Tityus stigmurus, with chelating properties for Cu2+ ion and immunomodulatory properties. The therapeutic application of chelating molecules is related to cases of acute or chronic intoxication by metals, neurodegenerative diseases, hematological diseases, healing of skin wounds, cardiovascular diseases, and cancer. In this approach, the chelating activity of TanP was evaluated in relation to new metal ions (Fe2+ and Zn2+) of biological importance, as well as its antioxidant, hemostatic, immunomodulatory, and healing potential, aiming to expand the biological and biotechnological potential of this peptide. TanP (25 µM) was able to form stable complexes with Fe2+ in a ratio of 1:5 (TanP: Fe2+). Theoretical results suggest that TanP can work as a sensor to identify and quantify Fe2+ ions. The fluorescence intensity of TanP (1.12 µM) decreased significantly after the addition of Fe2+, obtaining the highest ratio 1: 7.4 (TanP: Fe2+) that led to the lowest fluorescence intensity. For Zn2+, no relevant spectral change was noted. TanP (50 µM) showed a maximum of 3% of hemolytic activity, demonstrating biocompatibility, as well as exhibiting a 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity of above 70% at all the concentrations tested (1-25 µM), and 89.7% iron-chelating activity at 25 µM and 96% hydroxyl radical-scavenging activity at 73.6 µM. In addition, TanP (12.5 and 25 µM) revealed an anticoagulant effect, prolonging the clotting time in prothrombin time and activated partial thromboplastin time assays, with no fibrinogenolytic activity. TanP (12.5 and 25 µM) induced the release of TNF-α by murine macrophages, in the absence of lipopolysaccharides, with a concentration-dependent increase and also stimulated the migration of 3T3 cells in the in vitro healing assay. Thus, TanP revealed a multifunctional potential, being useful as a prototype for the development of new therapeutic and biotechnological agents.

Effect of Gold Nanoparticle on 5-Fluorouracil-Induced Experimental Oral Mucositis in Hamsters.

BACKGROUND: Oral mucositis (OM) is a severe inflammation of the oral mucosal cells associated with chemotherapy and/or radiotherapy-induced toxicity, resulting in epithelial ulcers and higher risk of death from sepsis. The aim of the present study was to evaluate the nanoparticle (AuNp) effect on OM induced in hamsters. MATERIALS AND METHODS: 5-fluorouracil (5FU) was used on the first and second day of the experimental model in Golden sirian hamsters, and on the fourth day, mechanical trauma was applied to induce OM. The animals were divided into groups, i.e., polyvinylpyrrolidone (PVP), mechanical trauma (MT), 5FU, and groups treated with gold nanoparticles (AuNps) (62.5, 125, and 250 µg/kg). On the 10th day, animals were euthanized for macroscopic, histopathological, immunohistochemical, western blot, quantitative polymerase chain reaction (qRT-PCR), and AuNp quantification. RESULTS: AuNp (250 µg/kg) reduced TNF-α, IL-1ß, COX-2, NF-κB, TGF-ß, and SMAD 2/3; increased glutathione levels; decreased the expression of Kelch ECH-associated protein 1 (KEAP1); and induced heme oxygenase 1 (HMOX-1) and NAD (P) H quinone oxidoreductase 1 (NQO1) genes. CONCLUSIONS: AuNp (250 µg/kg) prevented 5-FU-induced OM in hamsters and improved the parameters of inflammation and oxidative stress.

Caulerpa Cupressoides Var. Flabellata.

Green seaweeds are rich sources of sulfated polysaccharides (SPs) with potential biomedical and nutraceutical applications. The aim of this work was to evaluate the immunostimulatory activity of SPs from the seaweed, Caulerpa cupressoides var. flabellata on murine RAW 264.7 macrophages. SPs were evaluated for their ability to modify cell viability and to stimulate the production of inflammatory mediators, such as nitric oxide (NO), intracellular reactive oxygen species (ROS), and cytokines. Additionally, their effect on inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) gene expression was investigated. The results showed that SPs were not cytotoxic and were able to increase in the production of NO, ROS and the cytokines, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). It was also observed that treatment with SPs increased iNOS and COX-2 gene expression. Together, these results indicate that C. cupressoides var. flabellata SPs have strong immunostimulatory activity, with potential biomedical applications.