Lovastatin (LOV) is widely used for the treatment of hypercholesterolemia. The poor water solubility of LOV leads to its poor gastrointestinal absorption and results in poor bioavailability. In this study, a preparation of solid dispersions with acetylsalicylic acid (ASA) was studied to improve the dissolution rate of LOV. Solid dispersions were prepared using various mass ratios of both components through the grinding method. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRPD) were used to characterize prepared solid dispersions. Their dissolution behaviors were also compared. LOV and ASA formed a simple eutectic phase diagram as indicated by DSC. The results obtained from FTIR spectroscopy and XRPD showed no evidence of drug–drug interaction. The dissolution studies indicated that the in vitro dissolution rate of LOV released from solid dispersions containing 10, 20, 40 and 60 mass% LOV was improved compared with the drug alone.
28 February 2017 in Photochemistry and Photobiology
Single and double amino-bisphosphonates were synthesized and tested for coordination capabilities towards Ca2+, Mg2+, Cu2+ and Ni2+ metal ions by means of potentiometry, UV-vis spectroscopy, mass spectrometry (ESI-MS) and isothermal titration calorimetry (ITC), as well as for cytotoxic activity by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] assay. Half minimal inhibitory concentrations (IC50) were determined with respect to two cell lines (human melanoma A375 and human colorectal adenocarcinoma HT29). Basing the structure of compounds on a cyclohexane ring allowed for a slight reduction of high hydrophilic character of the studied bisphosphonates (BPs). The ligands efficiently bind the examined metal ions forming complex equilibria with diversified stoichiometry of equimolar, polynuclear species and biscomplexes. Both ligands as well as their Ca2+ and Mg2+ complexes show selective antiproliferative activity toward the studied cancer cell lines. Given the thermodynamic and biological data, it can be assumed that ligands are good candidates for linking compounds that may be used in the design of new drug delivery systems. In this approach, one bisphosphonate moiety acts as a bone-targeting molecule, while another molecule can be readily attached to the second donor function (primary amine or bisphosphonate).
Mucin 7 (encoded byMUC7) is a human salivary protein that has a role in the natural immune system. Fragments of mucin 7 exhibit antimicrobial activity against bacteria and yeast. Although the antimicrobial properties of peptides have been known and studied for decades, the exact mechanism of action of antimicrobial peptides (AMPs) is still unclear. It is known that some AMPs require divalent metal ions to activate their activity. Herein, we investigated three 15-mer MUC7 peptides, one of which (mother peptide, sequence, L3) is a synthetic analog of a fragment naturally excised from MUC7 (with His3, His8, and His 14) and its two structural analogs, containing only two histidine residues, His3, His13 and His8, His13 (L2 and L1, respectively). Since there is a correlation between lipophilicity, the presence of metal ions (such as Cu(II) and Zn(II)) and antimicrobial activity of AMP, antimicrobial properties of the studied peptides, as well as their complexes with Cu(II) and Zn(II) ions, were tested for activity against Gram-positive (Enterococcus faecalis, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans). The results were correlated with their lipophilicity. Coordination and thermodynamic studies (potentiometry, UV-Vis, CD) revealed the formation of mainly mononuclear complexes in solution for all studied systems with different stability in the physiological pH range.