Quantification of biofilm formation on silicone intranasal splints: An in vitro study

Objectives: Biofilms are associated with persistent infections and resistant to conventional therapeutic strategies. The aim of this study was to investigate the quantity of biofilm produced on silicone intranasal splints. Methods: Quantity of biofilm formation on silicone splints (SS) was tested on 15 strains of Staphylococcus aureus and Moraxella catarrhalis, respectively. Antimicrobial susceptibility testing was performed in accordance with European Committee on Antimicrobial Susceptibility Testing recommendations. Results: All tested strains formed different amounts of biofilm on SS: 66.7% S. aureus and 93.3% M. catarrhalis were weak biofilm producers and 33.3% S. aureus and 6.7% M. catarrhalis were moderate biofilm producers. S. aureus formed significantly higher quantity of biofilm compared with M. catarrhalis (p  Conclusion: Quantity of biofilm on SS is highly dependent on bacterial species and their resistance patterns. Future studies are needed to ascertain another therapeutic option for prophylaxis prior to SS placement

Design and In Vitro Biological Evaluation of a Novel Organotin(IV) Complex with 1-(4-Carboxyphenyl)-3-ethyl-3-methylpyrrolidine-2,5-dione

A novel triphenyltin(IV) compound with 1-(4-carboxyphenyl)-3-ethyl-3-methylpyrrolidine-2,5-dione was synthesized and characterized by IR, NMR spectroscopy, mass spectrometry, and elemental analysis. In vitro anticancer activity of ligand precursor and synthesized organotin(IV) compound was determined against tumor cell lines: human adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human breast cancer (MDA-MB-453), using microculture tetrazolium test (MTT) assay. The results indicate that complex exhibited very high antiproliferative activity against all tested cell lines with IC50 values in the range of 0.22 to 0.53 mu M. The highest activity organotin(IV) compound expressed against the HeLa cells (IC50=0.22 +/- 0.04 mu M). The ligand precursor did not show anticancer activity (IC50>200 mu M). Furthermore, fluorescence microscopy analysis of HeLa cells reveal that organotin(IV) complex induced apoptosis as a mode of cell death, which is consistent with the increase of cells in the sub-G1 phase

Electrochemical Characterization of Oxaprozin on Bare Gold Electrode and Electrode Modified with Bovine Serum Albumin

As the very first electrochemical investigation of oxaprozin, nonsteroidal anti-inflammatory drug, using cyclic voltammetry on gold electrode in 0.05 mol dm(-3) NaHCO3, the synthesized drug, its analytical standard and its content in Duraprox (R) tablets were characterized with one oxidation reaction and the three reduction reactions. All they exhibited the linear concentration dependency of anodic currents at 0.83V for the analytical standard and 0.85V for Duraprox (R) tablets in the range of concentrations 8.44 - 32.78x10(-6) mol dm(-3). The strong adsorption of bovine serum albumin (BSA) on gold electrode in 0.1 mol dm(-3) phosphate buffer solution (pH 7.4) is shown and concentration dependency of anodic currents of oxaprozin standard on BSA/Au is studied. Following the Langmuir adsorption thermodynamic equation, the binding constants of oxaprozin on BSA/Au electrode was calculated with the results 1.23x10(5) dm(3) mol(-1)

Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats

The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings

Electrochemical Characterization of Oxaprozin on Bare Gold Electrode and Electrode Modified with Bovine Serum Albumin

As the very first electrochemical investigation of oxaprozin, nonsteroidal anti-inflammatory drug, using cyclic voltammetry on gold electrode in 0.05 mol dm(-3) NaHCO3, the synthesized drug, its analytical standard and its content in Duraprox (R) tablets were characterized with one oxidation reaction and the three reduction reactions. All they exhibited the linear concentration dependency of anodic currents at 0.83V for the analytical standard and 0.85V for Duraprox (R) tablets in the range of concentrations 8.44 - 32.78x10(-6) mol dm(-3). The strong adsorption of bovine serum albumin (BSA) on gold electrode in 0.1 mol dm(-3) phosphate buffer solution (pH 7.4) is shown and concentration dependency of anodic currents of oxaprozin standard on BSA/Au is studied. Following the Langmuir adsorption thermodynamic equation, the binding constants of oxaprozin on BSA/Au electrode was calculated with the results 1.23x10(5) dm(3) mol(-1)

Oxaprozin: Synthesis, SAR study, physico-chemical characteristics and pharmacology

Oxaprozin (3-(4,5-difeniloksazol-2-yl)propanoic acid) is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of numerous inflammatory musculoskeletal diseases, including rheumatoid arthritis, osteoarthritis, tendonitis, ankylosing spondylitis and bursitis. It is the first representative member of the diaryl-substituted heterocyclic compounds, which have found clinical use as selective cyclooxygenase-2 (COX-2) inhibitors. U.S. Food and Drug Administration (FDA) approved its official use in 1992. Both anti-inflammatory and analgesic properties of oxaprozin are mainly due to the potent inhibition of COX. However, oxaprozin-induced benefits might be also regulated by other COX-independent pathways. It has been shown that oxaprozin induced direct proapoptotic effects in CD40L-treated human monocytes independently of COX inhibition. It also has several advantages in the treatment of inflammatory diseases in comparison to other NSAIDs such as aspirin, naproxen, indomethacin and phenylbutazone, which enabled oxaprozin to become one of the most used NSAIDs in America. Oxaprozin, as other members of the group of NSAIDs, can cause gastrointestinal complications, but significantly lower due to relatively high pKa value. In this paper, importance of oxaprozin in the treatment of arthritis and its pharmacokinetic properties were described, therewith its activity and side effects were compared with other commercially available anti-inflammatory drugs

The Influence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss <i>Hypnum cupressiforme</i> Extracts: In Vitro and In Silico Study

Numerous representatives of mosses, including Hypnum cupressiforme, have been used to alleviate different inflammation-related conditions. However, the mode of action underlying this anti-inflammatory potential has been poorly understood. Moreover, the influence of seasonality on the chemical composition and biological activity of mosses is generally overlooked. This study aimed to investigate the influence of seasonal changes (spring, summer, and autumn) on secondary metabolite composition and biological activities of ethyl acetate H. cupressiforme extracts. Antioxidant activity was measured using β-carotene bleaching assay, while MTT, NBT, ELISA, and Griess assays were carried out to explore the anti-neuroinflammatory and neuroprotective potential of extracts. Inhibitory activities on acetylcholinesterase and tyrosinase were assessed experimentally and by docking analysis. The highest content of secondary metabolites and antioxidant activity were observed in moss during the summer. Extracts inhibited the secretion of ROS, NO, TNF-α, and IL-6, alleviating the inflammatory potential of H2O2 and LPS in microglial and neuronal cells. Strong inhibitory effects on acetylcholinesterase and tyrosinase were observed in vitro. Docking analyses revealed high-affinity interactions of secondary metabolites present in H. cupressiforme with important enzyme residues. Altogether, these results reveal the neuroprotective potential and the significance of seasonal fluctuations on secondary metabolite content and biological activities in moss H. cupressiforme

Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety

Two series of cycloalkanespiro-5-hydantoins, namely cyclohexanespiro-5-hydantoins and cycloheptanespiro-5-hydantoins with a 4-substituted benzyl or a 2-(4-substituted phenyl)-2-oxoethyl group at N3 position, were synthesized and their effects on proliferation of human colon (HCT-116), leukemia (K562) and breast (MDA-MB-231) cancer cell lines were tested. For comparison, we also described the 5,5-diphenylhydantoin analogues. The structural features of the investigated compounds were characterized by elemental analysis, FT-IR, UV–Vis, 1 H and 13 C NMR spectroscopy and X-ray crystallography. Regarding their structure–activity relationships, it was shown that the substitution on the benzyl moiety with the methoxy, chloro or bromo group potentiated the antiproliferative activity relative to the parent compounds, while an increase in the size of the cycloalkyl group resulted mostly in a decrease of the antiproliferative activity. The single crystal X-ray analysis revealed the existence of dimers and chains formed by the N–H⋯O hydrogen bonds. The analysis of the molecular descriptors of Lipinski demonstrated that all investigated compounds obeyed the rule of five. To further understand their geometry and electronic structure, DFT calculations with B3LYP method using 6-311++G(d,p) basic set were performed. In this context, the UV–Vis spectra of the investigated compounds were analyzed in detail, whereby the predicted absorption spectra from DFT calculation matched the experimentally obtained ones, with a good correlation. The interesting physico-chemical and pharmacologically relevant properties of the investigated compounds warrant their further investigation.[http://technorep.tmf.bg.ac.rs/handle/123456789/4324]This is the peer-reviewed version of the following article: Lazić A, Radovanović L, Božić B, Božić-Nedeljković B, Vitnik V, Vitnik Ž, Rogan J, Valentić N, Ušćumlić G, Trišović N. Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety. in Journal of Molecular Structure. 2019;1180:48-62. [doi:10.1016/j.molstruc.2018.11.071

Design of novel multifunctional Oxaprozin delivery system based on dual-sensitive poly(2-hydroxypropyl acrylate/itaconic acid) hydrogels

Series of novel dual-sensitive poly(2-hydroxypropyl acrylate/itaconic acid) hydrogels were designed as multifunctional drug delivery system which can provide several advantages including drug protection, self-regulated oscillatory release and targeted delivery to a single entity. The hydrogels were synthesized by the free-radical crosslinking copolymerization and evaluated as carriers for hydrophobic drug, Oxaprozin, with specific controlled release properties. Structural, morphological, thermal, surface charge, swelling and antimicrobial properties of the hydrogels were investigated for unloaded and Oxaprozin-loaded samples. Swelling studies demonstrated pH- and temperature-sensitivity of drug-free and drug-loaded P(HPA/IA) hydrogels. The results of swelling and oscillatory swelling, and swelling behavior of drug-free, and drug-loaded hydrogels in simulated gastrointestinal conditions, and in vitro Oxaprozin release studies confirmed these hydrogels as a highly effective colon-specific drug delivery system with excellent performance of long-term controlled release. These unique properties make the P(HPA/IA) hydrogels highly attractive materials for developing multifunctional drug delivery systems

Chemical characterization and in vitro immunomodulatory effects of different extracts of moss Hedwigia ciliata (Hedw.) P. Beauv. from the Vršačke Planine Mts., Serbia.

Bioactive compounds from natural sources are of great importance because of their potential pharmacological activity and tremendous structural diversity. In this study, the chemical composition of different moss extracts of Hedwigia ciliata P. Beauv. have been examined, as well as their antioxidant, antineurodegenerative/anti-neuroinflammatory, antidiabetic, and antiproliferative potential. The extracts were prepared by Soxhlet extractor using solvents of different polarity. Chemical characterization of the extracts revealed the presence of phenolics and flavonoid compounds, together with triterpenoids as secondary metabolites of high biological activity. Significant antioxidant properties of all the extracts were exhibited using the β-carotene assay. The highest activities were found for water:ethanol extract (with the highest inhibition rate of 96%), but also significant inhibition was measured for ethanol and ethyl acetate extracts (80% and 70%, respectively). Confirmation of biocompatibility of investigated moss extracts has been performed using normal human fibroblast cell line, MRC-5. The H. ciliata extracts exhibited significant antiproliferative activity (~ 50%) against the MDA-MB-231 (human breast adenocarcinoma cell line), which has not previously been reported elsewhere. The Griess assay confirmed the potential anti-neuroinflammatory activity of the extracts, as significant effects in reducing NO production by LPS-stimulated BV2 (normal murine microglia cell line) was observed. This data is in line with noted antineurodegenerative potential measured by the inhibition of acetylcholinesterase (with the highest inhibition rate of 60% for ethyl acetate extract) and tyrosinase (with the highest inhibition rate of 70% for ethanol extract). Additionally, the H. ciliata extracts exhibited significant antidiabetic effect mediated by α-glucosidase inhibition (with the highest inhibition rate of 80% for ethyl acetate extract). The obtained data suggest the presence of immunomodulatory effects of the moss extracts in vitro, which allows the design of new experiments aimed at detecting and characterizing bioactive compounds of the extracts and additionally elucidate detailed mechanisms of their effects