Construction of coral rod-like MoS2@HA nanowires hybrids for highly effective green antisepsis.

Antibacterial materials have been rapidly emerging as a primary component in the mitigation of bacterial pathogens, and green functional materials play a vital role in the antibacterial field. In this study, biocompatible hydroxyapatite nanowires (HANW) was used as a carrier, a coral rod-like nanowires hybrid of MoS2 and HANW (CR-MoS2@HANW) was synthesized via a facile two-step hydrothermal approach. After being characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmet-Teller (BET) and thermogravimetric (TG) analysis, the antibacterial activity and environmental compatibility were assessed. It was found that MoS2 nanosheets were in-situ assembled onto surface of HA nanowires, and the obtained nanohybrid exhibited excellent stability. CR-MoS2@HANW endowed a desirable long-term antibacterial activity against both gram-negative E. coli and gram-positive S. aureus. It was sufficient to inhibit the growth of bacteria within 72 h, and nanohybrids effectively promoted the growth of plants. In summary, the combination of MoS2 and HANW created a novel eco-friendly nanohybrids that could be applied as a promising multi-functional green antisepsis. And the CR-MoS2@HANW possessed enormous potential for biomedical applications.

Poly(ionic liquid)-Based Efficient and Robust Antiseptic Spray.

Exploring efficient and robust antibacterial materials is crucially important for human health and ecological security. Compared with intrinsically antibacterial materials, materials modified with antibacterial agents either by chemical or physical modification can simultaneously maintain basic functions and antibacterial properties. In particular, physical modification with antiseptic sprays is quite suitable for large-size objects in our daily life but restricted by high volatility of the antibacterial agents or poor adhesion strength between the antibacterial agents and the targeted objects. In this paper, we report a poly(ionic liquid) (PIL-Cn)-based efficient and robust antiseptic spray that exhibits long-term antibacterial properties against both Gram-positive and Gram-negative bacteria on diverse substrates, including glass, PE, and cotton. It is believed that this work will provide an alternative for current antiseptic sprays for usage in our daily life and hospitals.

Acriflavine-loaded solid lipid nanoparticles: preparation, physicochemical characterization, and anti-proliferative properties.

Acriflavine (ACF) is an antiseptic compound with the potential antitumor activity which is used for the fluorescent staining of RNA due to its dominant fluorescent emission at ∼515 nm. Here, solid lipid nanoparticles (SLNs) containing ACF (ACF-SLNs) were prepared and their physicochemical properties, potential geno/cytotoxicity, as well as the fluorescent properties were investigated. FITC-annexin V/PI staining and cell cycle assays were carried out to find the type of cellular death caused. Particle size analysis and SEM images revealed that spherical ACF-SLNs had a homogeneous dispersion with a mean diameter of 106 ± 5.7 nm. Drug loading (DL) of 31.25 ± 4.21 mg/mL and high encapsulation efficiency (EE%) (89.75 ± 5.44) were found. ACF-SLNs physically were relatively stable in terms of dispersion, size, and EE. The uptake study demonstrated the potential use of fluorescent ACF-SLNs in bio-distribution studies. MTT assay showed that plain ACF could induce growth inhibition of A549 cells with IC50 of 8.5, 6, and 4.5 µMol after 24, 48, and 72 hours, respectively, while ACF-SLNs had stable cytotoxic effects after 48 hours. ACF-SLNs induced remarkable apoptosis and even necrosis after 48 h. Conclusively, ACF-SLNs with acceptable physicochemical features showed increased bioimpacts after 48 h compared to plain ACF.

Combining Powder Formulations of Drugs with Food and Beverages to Improve Palatability.

The taste of medicines can significantly affect patient adherence. Pediatric patients often cannot take powder medicines because of their unpleasant taste. Therefore, patients' parents and health care professionals, including pharmacists, often combine medicines with food or beverages to make them easier for pediatric patients to consume because this can reduce their unpleasant taste. The purpose of this study was to evaluate the palatability of powder formulations of azithromycin and carbocysteine and explore their combination with food or beverages to improve palatability for pediatric patients. We quantitatively evaluated the palatability of powder formulations by performing the gustatory sensation test using the visual analog scale score. The gustatory sensation tests were performed on 16 healthy adult volunteers (age 23.0 ± 2.6 years) and indicated that some food and beverages improved the palatability of the powder formulations of azithromycin and carbocysteine. The results of this study indicate that ice cream improves the palatability of azithromycin, while yogurt improves the palatability of carbocysteine. Moreover, the subjects recommended these same combinations for pediatric patients. This study suggests that some foods and beverages improve the palatability of powder formulations, thereby decreasing the possibility that pediatric patients will refuse medications because of their unpleasant taste.

Advancements in the Development of Non-Nitrogen-Based Amphiphilic Antiseptics to Overcome Pathogenic Bacterial Resistance.

The prevalence of quaternary ammonium compounds (QACs) as common disinfecting agents for the past century has led bacteria to develop resistance to such compounds. Given the alarming increase in resistant strains, new strategies are required to combat this rise in resistance. Recent efforts to probe and combat bacterial resistance have focused on studies of multiQACs. Relatively unexplored, however, have been changes to the primary atom bearing positive charge in these antiseptics. Here we review the current state of the field of both phosphonium and sulfonium amphiphilic antiseptics, both of which hold promise as novel means to address bacterial resistance.

An Investigation into Rigidity-Activity Relationships in BisQAC Amphiphilic Antiseptics.

Twenty-one mono- and biscationic quaternary ammonium amphiphiles (monoQACs and bisQACs) were rapidly prepared in order to investigate the effects of rigidity of a diamine core structure on antiseptic activity. As anticipated, the bioactivity against a panel of six bacteria including methicillin-resistant Staphylococcus aureus (MRSA) strains was strong for bisQAC structures, and is clearly correlated with the length of non-polar side chains. Modest advantages were noted for amide-containing side chains, as compared with straight-chained alkyl substituents. Surprisingly, antiseptics with more rigidly disposed side chains, such as those in DABCO-12,12, showed the highest level of antimicrobial activity, with single-digit MIC values or better against the entire bacterial panel, including sub-micromolar activity against an MRSA strain.

Synthesis and Characterization of Thiolated PVP-Iodine Complexes: Key to Highly Mucoadhesive Antimicrobial Gels.

The aim of this study was to synthesize iodine containing polymeric excipients for mucosal treatment of microbial infection exhibiting a prolonged mucosal residence time by forming an adhesive gel on the mucosal surface. In order to achieve this aim, 2-(2 acryloylamino-ethyldisulfanyl)-nicotinic acid (ACENA) was copolymerized with N-vinylpyrrolidone (NVP) to obtain thiolated polyvinylpyrrolidone (PVP) for complexation with iodine. The average molecular mass of different thiolated PVP variants was determined by size exclusion chromatography. The structure of thiolated PVP was confirmed by 1H NMR. Thiolated PVP variants were characterized for thiol content, cytotoxicity, iodine loading capacity, rheological behavior, and adhesion time on mucosa. The highest achieved degree of thiolation was 610 ± 43 µmol/g, and the maximum recorded iodine loading was 949 ± 31 µmol/g of polymer. Thiolated PVP variants (0.5% m/v) showed no toxicity after incubation on Caco-2 cells for the period of 3 and 24 h, respectively. Thiolated PVP and thiolated PVP-iodine complexes exhibited a 5.4- and 4.4-fold increased dynamic viscosity in porcine mucus in comparison to PVP and PVP-iodine complex, respectively. Compared to PVP and PVP-iodine complex thiol-functionalized PVP and PVP-iodine complexes demonstrated significantly prolonged attachment to mucosal surface over a period of 3 h. Thiol functionalized PVP proved to be a promising novel excipient for complexation with iodine and to exhibit strongly improved mucoadhesive properties.

Hybrid BisQACs: Potent Biscationic Quaternary Ammonium Compounds Merging the Structures of Two Commercial Antiseptics.

Benzalkonium chloride (BAC) and cetyl pyridinium chloride (CPC) are two of the most common household antiseptics, but show weaker efficacy against Gram-negative bacteria as well as against methicillin-resistant Staphylococcus aureus (MRSA) strains, relative to other S. aureus strains. We prepared 28 novel quaternary ammonium compounds (QACs) that represent a hybrid of these two structures, using 1- to 2-step synthetic sequences. The biscationic (bisQAC) species prepared show uniformly potent activity against six bacterial strains tested, with nine novel antiseptics displaying single-digit micromolar activity across the board. Effects of unequal chain lengths of two installed side chains had less impact than the overall number of side chain carbon atoms present, which was optimal at 22-25 carbons. This is further indication that simple refinements to multiQAC architectures can show improvement over current household antiseptics.

Zinc oxide nanoparticles: Synthesis, antiseptic activity and toxicity mechanism.

Zinc oxide (ZnO), as a material with attractive properties, has attracted great interest worldwide, particularly owing to the implementation of the synthesis of nano-sized particles. High luminescent efficiency, a wide band gap (3.36eV), and a large exciton binding energy (60meV) has triggered intense research on the production of nanoparticles using different synthesis methods and on their future applications. ZnO nanomaterials can be used in industry as nano-optical and nano-electrical devices, in food packaging and in medicine as antimicrobial and antitumor agents. The increasing focus on nano zinc oxide resulted in the invention and development of methods of nanoparticles synthesis. Recently, various approaches including physical, chemical and biological ("green chemistry") have been used to prepare ZnO nanocomposites with different morphologies. The obtained nanoparticles can be characterized with a broad range of analytical methods including dynamic light scattering (DLS), electron microscopy (TEM, SEM), UV-VIS spectroscopy, X-ray diffraction (XRD) or inductively coupled plasma with mass spectrometry (ICP-MS). With these it is possible to obtain information concerning the size, shape and optical properties of nanoparticles. ZnO NPs exhibit attractive antimicrobial properties against bacteria (Gram-positive and Gram-negative) and fungi. Zinc oxide nanocomposites show also selective toxicity toward normal and cancerous cells, which is explained by reactive oxygen formation (ROS). Yet despite the potentially interesting antitumor activity of ZnO nanoparticles, it has been proven that they can be also cytotoxic and genotoxic for multiple types of human cells (i.e. neuronal or epithelial cells). This paper reviews the methods of synthesizing zinc oxide nanocomposites as well as their characteristics, antimicrobial activity and cytotoxicity against normal and tumor cells.

Synthesis of New Fluoro-Benzimidazole Derivatives as an Approach towards the Discovery of Novel Intestinal Antiseptic Drug Candidates.

In the present study, nineteen new fluoro-benzimidazole derivatives, including nifuroxazide analogs, were synthesized by microwave-supported reactions and tested against a panel of pathogenic microorganisms consisting of resistant strains. The synthesized compounds were characterized and identified by FT-IR, 1H- and 13C-NMR, mass spectroscopy, and elemental analyses, respectively. In vitro antimicrobial and cytotoxic effects of the synthesized compounds were determined by microdilution and by [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] (MTT) assay. The compound 4-[5(6)-fluoro-1H-benzimidazol-2-yl)-N'-(2- methylbenzylidene)]benzohydrazide (18) showed particularly high inhibitory activity against the gastro-intestinal pathogens, such as Escherichia coli O157:H7, Escherichiacoli ATCC 8739, Escherichia coli ATCC 35218 and Salmonella typhimurium ATCC 13311 standard strains, with minimum inhibitory concentrations (MIC90) ranging from 0.49-0.98 µg/mL. The microbial panel contained a total of ten pathogens including Klebsiella sp., Mycobacterium sp., MRSA, etc., for which the level of inhibitory activity measured was higher than that exhibited by the tested concentrations (MIC > 1000 µg/mL). In vitro cytotoxicity results revealed that the inhibitory concentration (IC50) value (210.23 µg/mL) of compound 18 against CCD 841 CoN cells (human intestinal epithelial cell line) is about 430 times higher than its MIC90 value against the tested Escherichia coli strains. Furthermore, the docking study of compound 18 suggested that its structure is very compatible with the active site pocket of the phosphofructokinase-2 enzyme.

Preparation and characterization of hemoglobin-silver composites as biocompatible antiseptics.

Microbial contamination has been a major challenge in a wide variety of fields such as biomedical and biomaterial applications. The development of biomaterials that possess excellent antibacterial ability and biocompatibility is of great importance to enhance the service life of biomaterials. In this study, the main protein component of red blood cells, hemoglobin (Hb), was employed to prepare Ag-Hb nanocomposites as novel biocompatible antiseptics. The formation of Ag-Hb nanocomposites on the titanium substrate are confirmed by field-emission scanning electron microscopy, Fourier transformed infrared spectroscopic, contact angles, and inductively coupled plasma atomic emission spectrometry analysis. The Ag-Hb titanium shows potent antibacterial ability against planktonic bacteria in the suspension and ability to prevent bacterial adhesion. Moreover, the Ag-Hb titanium shows excellent biocompatibility, which supports healthy osteoblast cellular activity and osteoblast differentiation. The results indicate that the Ag-Hb nanocomposites can be potentially useful for the fabrication of biomaterials for long-term applications.

Nanoporous aerogel as a bacteria repelling hygienic material for healthcare environment.

Healthcare-associated infections (HAIs) caused by pathogenic bacteria are a worldwide problem and responsible for numerous cases of morbidity and mortality. Exogenous cross-contamination is one of the main mechanisms contributing to such infections. This work investigates the potential of hydrophobically modified nanoporous silica aerogel as an antiadhesive hygienic material that can inhibit exogenous bacterial contamination. Nanoporous silica aerogels were synthesized via sol-gel polymerization of tetraethyl orthosilicate and hydrophobized using trimethylsilyl chloride. Bacterial adhesion characteristics were evaluated via dip-inoculation in suspensions of Gram-negative Escherichia coli O157:H7 and Gram-positive Staphylococcus aureus. The attachment of E. coli O157:H7 and S. aureus to hydrophobic nanoporous silica aerogel (HNSA) was found to be significantly lower than that to hydrophilic and hydrophobic nonporous silica materials: 99.91% (E. coli O157:H7) and 99.93% (S. aureus) reduction in comparison to hydrophilic nonporous silica, and 82.95% (E. coli O157:H7) and 84.90% (S. aureus) reduction in comparison to hydrophobic nonporous silica. These results suggest that the use of HNSA as surfaces that come into contact with bacterial pathogens in the healthcare environment can improve bacterial hygiene, and therefore may reduce the rate of HAIs.

Supramolecular elastomer based on polydimethylsiloxanes (SESi) film: synthesis, characterization, biocompatibility, and its application in the context of wound dressing.

Supramolecular elastomer based on polydimethylsiloxanes (SESi) is a kind of novel elastomer cross-linked by the multihydrogen bonds supplied by the functional groups linked to the end of the PDMS chains, such as amide, imidazolidone, pending urea (1,1-dialkyl urea), and bridging urea (1,3-dialkyl urea). SESi showed lower glass transition temperature (T g) at about -113 °C because of the softer chain of PDMS, and could show real rubber-like elastic behaviors and acceptable water vapor transmission rate under room temperature. The high biocompatibility of SESi in the form of films was demonstrated by the cytotoxicity evaluation (MTT cytotoxicity assay and direct contact assay), hemolysis assay, and skin irritation evaluation. Based on detailed comparisons between commercial Tegaderm(™) film and SESi film using a full-thickness rat skin model experiment, it was found that SESi film showed similar wound contraction rate as that of Tegaderm(™) film on day seven, 10, and 14; only on day five, SESi film showed a significant (p < 0.05) lower wound contraction rate. And, the wounds covered with SESi film were filled with new epithelium without any significant adverse reactions, similar with that of Tegaderm(™) film.

Dermaseptin S4 derivative K4K20S4: a potential candidate for development of a new microbicide contraceptive agent--an in vitro study.

BACKGROUND AND OBJECTIVES: Sexually transmitted infections (STIs) and unplanned pregnancies have serious effects on the reproductive health of women. The present study was undertaken with a view to develop an effective means of prevention. The microbicidal and contraceptive potential of cationic peptides from frog's skin, namely, dermaseptin S4 and its derivatives were investigated in vitro.: STUDY DESIGN Different bacterial and fungal strains were resorted to for determining the antimicrobial activity of the new compounds. The spermicidal activities of the latter were assessed using normal human semen samples, and their toxic effects were identified in a HeLa culture. RESULTS: All S4 derivatives elicited concentration-dependent spermicidal and antimicrobial activities at microgram concentrations. The highest levels recorded for both types of activity were displayed by K4K20S4, and the lowest levels were exhibited by D4D20S4 and S4(5-28). Cytotoxicity assays revealed that some of these compounds were significantly safer than nonoxynol-9 (N-9). CONCLUSIONS: The ability of these peptides to instantaneously kill human sperm and STI pathogens at low concentrations indicates that their application as active ingredients in vaginal contraceptive preparations could induce considerably better effects than N-9.

Prolonging the duration of preventing bacterial adhesion of nanosilver-containing polymer films through hydrophobicity.

A superhydrophobic coating composed of silver nanoparticles was developed on copper from fluorinated multilayered polyelectrolyte films to examine its performance in preventing microbial adhesion. Antibacterial and antibiofouling experiments for this novel coating were conducted with SRB. From the disk diffusion tests (for 48 h), it was found that, compared to the traditional coating composed of nanosilver, this novel coating significantly improved antibacterial performance and long-term effectiveness. The oxidation states of the immobilized silver in polyelectrolyte multilayer films were investigated with X-ray photoelectron spectroscopy (XPS), and the stability of the immobilized silver was evaluated through a leaching test. It was found that if silver was exposed to aqueous environments some ionic silver species would be produced and released. The ion release kinetics showed that the duration of sustained release of antibacterial Ag ions from the novel coatings was prolonged, which was why they had more long-term antibacterial performance.

From triclosan toward the clinic: discovery of nonbiocidal, potent FabI inhibitors for the treatment of resistant bacteria.

In this paper, we present some elements of our optimization program to decouple triclosan's specific FabI effect from its nonspecific cytotoxic component. The implementation of this strategy delivered highly specific, potent, and nonbiocidal new FabI inhibitors. We also disclose some preclinical data of one of their representatives, 83, a novel antibacterial compound active against resistant staphylococci and some clinically relevant Gram negative bacteria that is currently undergoing clinical trials.

Improved methods for thermal rearrangement of alicyclic α-hydroxyimines to α-aminoketones: synthesis of ketamine analogues as antisepsis candidates.

Ketamine is an analgesic/anesthetic drug, which, in combination with other drugs, has been used as anesthetic for over 40 years. Ketamine induces its analgesic activities by blocking the N-methyl-D-aspartate (NMDA) receptor in the central nervous system (CNS). We have reported that low doses of ketamine administrated to patients before incision significantly reduced post-operative inflammation as reflected by reduced interleukin-6 (IL-6) sera-levels. Our data demonstrated in a rat model of Gram-negative bacterial-sepsis that if we inject a low dose of ketamine following bacterial inoculation we reduce mortality from approximately 75% to 25%. Similar to what we have observed in operated patients, the levels of TNF-α and IL-6 in ketamine-treated rats were significantly lower than in septic animals not treated with ketamine. On the base of these results, we have designed and synthesized series of new analogues of ketamine applying a thermal rearrangement of alicyclic α-hydroxyimines to a-aminoketones in parallel arrays. One of the analogues (compound 6e) displayed high activity in down-regulating the levels of IL-6 and TNF-α in vivo as compared to ketamine.

Acridine: a versatile heterocyclic nucleus.

Acridine is a heterocyclic nucleus. It plays an important role in various medicines. A number of therapeutic agents are based on acridine nucleus such as quinacrine (antimalarial), acriflavine and proflavine (antiseptics), ethacridine (abortifacient), amsacrine and nitracine (anticancer), and tacrine. Acridine is obtained from high boiling fraction of coal tar. It is also obtained in nature from plant and marine sources. Acridine undergoes a number of reactions such as nucleophilic addition, electrophilic substitution, oxidation, reduction, reductive alkylation and photoalkylation. The present review article summarizes the synthesis, reaction, literature review and pharmaceutical importance of acridine.

Local drug delivery system for the treatment of osteomyelitis: In vitro evaluation.

Local antimicrobial delivery is a potential area of research conceptualized to provide alternative and better methods of treatment for cases, as osteomyelitis where avascular zones prevent the delivery of drugs from conventional routes of administration. Drug-loaded polymers and calcium phosphates as hydroxyapatites have been tried earlier. Bioactive glasses are bone-filling materials used for space management in orthopedic and dental surgery. A new bioactive glass (SSS2) was synthesized and fabricated into porous scaffold with a view to provide prolonged local delivery of gatifloxacin and fluconazole as suitable for the treatment of osteomyelitis. The new SSS2 was characterized by Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analyses. In addition, the bioactivity of the SSS2 glass and resulting scaffold was examined by in vitro acellular method and ascertained by FTIR and XRD. The pore size distribution was analysed by mercury intrusion porosimetry and the release of drugs from scaffolds were studied in vitro. The glass and the resulting scaffolds were bioactive indicating that they can bond with bone in vivo. The scaffolds were porous with pores predominantly in the range of 10-60 µm, released the drugs effectively for 6 weeks and deemed suitable for local delivery of drugs to treat osteomyelitis.

Antiseptic properties of two calix[4]arenes derivatives on the human coronavirus 229E.

Facing the lack in specific antiviral treatment, it is necessary to develop new means of prevention. In the case of the Coronaviridae this family is now recognized as including potent human pathogens causing upper and lower respiratory tract infections as well as nosocomial ones. Within the purpose of developing new antiseptics molecules, the antiseptic virucidal activity of two calix[4]arene derivatives, the tetra-para-sulfonato-calix[4]arene (C[4]S) and the 1,3-bis(bithiazolyl)-tetra-para-sulfonato-calix[4]arene (C[4]S-BTZ) were evaluated toward the human coronavirus 229E (HCoV 229E). Comparing these results with some obtained previously with chlorhexidine and hexamidine, (i) these two calixarenes did not show any cytotoxicity contrary to chlorhexidine and hexamidine, (ii) C[4]S showed as did hexamidine, a very weak activity against HCoV 229E, and (iii) the C[4]S-BTZ showed a stronger activity than chlorhexidine, i.e. 2.7 and 1.4log10 reduction in viral titer after 5min of contact with 10⁻³mol L⁻¹ solutions of C[4]S-BTZ and chlorhexidine, respectively. Thus, the C[4]S-BTZ appeared as a promising virucidal (antiseptic) molecule.