Iodine/soluble starch cryogel: An iodine-based antiseptic with instant water-solubility, improved stability, and potent bactericidal activity.

Iodine (I2) as a broad-spectrum antiseptic has been widely used for treating bacterial infections. However, I2 has low water-solubility and sublimes under ambient conditions, which limits its practical antibacterial applications. The highly specific and sensitive reaction between I2 and starch discovered 200 years ago has been extensively applied in analytical chemistry, but the antibacterial activity of the I2-starch complex is rarely investigated. Herein, we develop a novel type of iodine-based antiseptics, iodine-soluble starch (I2-SS) cryogel, which can dissolve in water instantly and almost completely kill bacteria in 10 min at 2 µg/mL of I2. Although KI3 and the commercially available povidone­iodine (I2-PVP) solutions show similar antibacterial efficacy, the high affinity of I2 to SS largely enhances the shelf stability of the I2-SS solution with ∼73 % I2 left after one-week storage at room temperature. In sharp contrast, ∼8.5 % and âˆ¼2.5 % I2 are detected in KI3 and I2-PVP solutions, respectively. Mechanistic study reveals that the potent antibacterial effect of I2-SS originates from its attack on multiple bacterial targets. The outstanding antibacterial activity, capability of accelerating wound healing, and good biocompatibility of I2-SS are verified through further in vivo experiments. This work may promote the development of next-generation iodine-based antiseptics for clinical use.

Peripheral positions encode transport specificity in the small multidrug resistance exporters.

In secondary active transporters, a relatively limited set of protein folds have evolved diverse solute transport functions. Because of the conformational changes inherent to transport, altering substrate specificity typically involves remodeling the entire structural landscape, limiting our understanding of how novel substrate specificities evolve. In the current work, we examine a structurally minimalist family of model transport proteins, the small multidrug resistance (SMR) transporters, to understand the molecular basis for the emergence of a novel substrate specificity. We engineer a selective SMR protein to promiscuously export quaternary ammonium antiseptics, similar to the activity of a clade of multidrug exporters in this family. Using combinatorial mutagenesis and deep sequencing, we identify the necessary and sufficient molecular determinants of this engineered activity. Using X-ray crystallography, solid-supported membrane electrophysiology, binding assays, and a proteoliposome-based quaternary ammonium antiseptic transport assay that we developed, we dissect the mechanistic contributions of these residues to substrate polyspecificity. We find that substrate preference changes not through modification of the residues that directly interact with the substrate but through mutations peripheral to the binding pocket. Our work provides molecular insight into substrate promiscuity among the SMRs and can be applied to understand multidrug export and the evolution of novel transport functions more generally.

Molecular mechanism underlying the TLR4 antagonistic and antiseptic activities of papiliocin, an insect innate immune response molecule.

SignificanceSimilar to mammalian TLR4/MD-2, the Toll9/MD-2-like protein complex in the silkworm, Bombyx mori, acts as an innate pattern-recognition receptor that recognizes lipopolysaccharide (LPS) and induces LPS-stimulated expression of antimicrobial peptides such as cecropins. Here, we report that papiliocin, a cecropin-like insect antimicrobial peptide from the swallowtail butterfly, competitively inhibits the LPS-TLR4/MD-2 interaction by directly binding to human TLR4/MD-2. Structural elements in papiliocin, which are important in inhibiting TLR4 signaling via direct binding, are highly conserved among insect cecropins, indicating that its TLR4-antagonistic activity may be related to insect Toll9-mediated immune response against microbial infection. This study highlights the potential of papiliocin as a potent TLR4 antagonist and safe peptide antibiotic for treating gram-negative sepsis.

Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract.

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial ß-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.

Effect of chlorhexidine gluconate on mechanical and anti-microbial properties of thermoplastic cassava starch.

Antimicrobial thermoplastic starch (TPS) was developed using cassava starch, glycerol, and chlorhexidine gluconate (CHG) blend. CHG was added at concentrations of 1%, 5%, 10%, and 20% (wt./wt.) as an antimicrobial additive. The tensile strength and hardness of the blended samples increased with the chlorhexidine gluconate content, especially for 1% CHG. wt./wt. (12.6 MPa and 94, respectively). The TPS/CHG20 blend exhibited a large phase of CHG and recrystallization of TPS. The water solubility decreased with the addition of CHG. Nuclear magnetic resonance data confirmed a reaction between the hydroxyl groups of TPS and the amino groups of CHG. The TPS/CHG20% exhibited an inhibition zone for three bacterial types (Staphylococcus aureus, Escherichia coli, and Bacillus cereus) and three fungal types (Rhizopus oligosporus, Aspergillus oryzae, and Candida albicans). CHG acted simultaneously as a chain extender and an antimicrobial additive for TPS, improving its tensile strength, hardness, and anti-microbial properties.

Effects of emulsion, dispersion, and blend electrospinning on hyaluronic acid nanofibers with incorporated antiseptics.

Nanofibrous materials are used in drug delivery as carriers of active ingredients. These can be incorporated into the materials with various electrospinning methods that differ mainly in the way spinning solutions are prepared. Each method affects primarily the encapsulation efficiency and distribution of active ingredients in the materials. This study focuses on the incorporation of octenidine dihydrochloride (OCT) and triclosan (TRI) into nanofibrous materials electrospun from native hyaluronic acid emulsions, dispersions, and blends. OCT had no substantial effect on fiber morphology, which is affected by the solvent system. All OCT encapsulation efficiencies were comparable (approximately 90%). TRI encapsulation efficiencies varied greatly depending on the method used. Merely 3% of TRI was encapsulated when it was spun from a dispersion. Encapsulation efficiency was higher, and TRI was incorporated in clusters when an emulsion was used. The best result was achieved with a blend, in which case 96% of TRI was encapsulated.

Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2.

Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required. ( https://clinicaltrials.gov/ct2/show/NCT04707742 ; Identifier: NCT04707742).

Antiseptic chitosan bandage for preventing topical skin infections.

Infections on the wound surface are the major problem in restricting the healing process. To reduce the transmission and treat the infection, we have developed 0.05% and 0.1% octenidine dihydrochloride (Ocd) incorporated chitosan (Cs) based flexible bandages. Ocd is extensively used skin antiseptic for its mode of action over a broad spectrum of antimicrobial activity. The prepared antiseptic Cs-Ocd bandage was characterized using Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). In addition, swelling, degradation, cytocompability, antibacterial, and anti-biofilm property of the developed bandages were studied. This highly porous nature of Cs-Ocd bandage showed enhanced swelling property, slow degradation profile and controlled release of Ocd. The prepared antiseptic bandage exhibited synergistic effect showing good hemostatic potential with Cs, excellent antimicrobial and anti-biofilm activity with Ocd against Staphylococcus aureus (S. aureus) and Candida auris (C. auris). Thus, the developed Cs-Ocd bandage can be used as potential antiseptic bandage for skin infections.

Soft Surface Nanostructure with Semi-Free Polyionic Components for Sustainable Antimicrobial Plastic.

Surface antimicrobial materials are of interest as they can combat the critical threat of microbial contamination without contributing to issues of environmental contamination and the development drug resistance. Most nanostructured surfaces are prepared by post fabrication modifications and actively release antimicrobial agents. These properties limit the potential applications of nanostructured materials on flexible surfaces. Here, we report on an easily synthesized plastic material with inherent antimicrobial activity, demonstrating excellent microbicidal properties against common bacteria and fungus. The plastic material did not release antimicrobial components as they were anchored to the polymer chains via strong covalent bonds. Time-kill kinetics studies have shown that bactericidal effects take place when bacteria come into contact with a material for a prolonged period, resulting in the deformation and rupture of bacteria cells. A scanning probe microscopy analysis revealed soft nanostructures on the submicron scale, for which the formation is thought to occur via surface phase separation. These soft nanostructures allow for polyionic antimicrobial components to be present on the surface, where they freely interact with and kill microbes. Overall, the new green and sustainable plastic is easily synthesized and demonstrates inherent and long-lasting activity without toxic chemical leaching.

Chitosomes-In-Chitosan Hydrogel for Acute Skin Injuries: Prevention and Infection Control.

Burns and other skin injuries are growing concerns as well as challenges in an era of antimicrobial resistance. Novel treatment options to improve the prevention and eradication of infectious skin biofilm-producing pathogens, while enhancing wound healing, are urgently needed for the timely treatment of infection-prone injuries. Treatment of acute skin injuries requires tailoring of formulation to assure both proper skin retention and the appropriate release of incorporated antimicrobials. The challenge remains to formulate antimicrobials with low water solubility, which often requires carriers as the primary vehicle, followed by a secondary skin-friendly vehicle. We focused on widely used chlorhexidine formulated in the chitosan-infused nanocarriers, chitosomes, incorporated into chitosan hydrogel for improved treatment of skin injuries. To prove our hypothesis, lipid nanocarriers and chitosan-comprising nanocarriers (≈250 nm) with membrane-active antimicrobial chlorhexidine were optimized and incorporated into chitosan hydrogel. The biological and antibacterial effects of both vesicles and a vesicles-in-hydrogel system were evaluated. The chitosomes-in-chitosan hydrogel formulation demonstrated promising physical properties and were proven safe. Additionally, the chitosan-based systems, both chitosomes and chitosan hydrogel, showed an improved antimicrobial effect against S. aureus and S. epidermidis compared to the formulations without chitosan. The novel formulation could serve as a foundation for infection prevention and bacterial eradication in acute wounds.

Propolis: Properties and composition, health benefits and applications in fish nutrition.

Propolis is a viscous, waxy, resinous substance that is produced from the exudates of flowers and buds by the action of salivary enzymes of honey bees. Propolis may differ in color (brown, red or green), with color being influenced by the chemical composition and age of the product. Propolis has a special distinctive odor owing to the high concentration of volatile essential oils. It is composed of 5% pollen grains, 10% essential and aromatic oils, 30% wax, 50% resin and balsams, and other minor trace substances. Natural propolis products may be useful for a range of applications in aquaculture systems instead of relying on the application of synthetic compounds to manage many ailments that affect business profitability. It has been reported in several studies that propolis enhances performance, economics, immunity response and disease resistance in different fish species. This present review discusses the functional actions of propolis and the prospects of its use as an antimicrobial, antioxidant, immune-modulatory, antiseptic, antiparasitic, anti-inflammatory and food additive in aquaculture production. In summary, propolis could be a natural supplement that has the potential to improve fish health status and immunity thereby enhancing growth and productivity of the fish industry as well as economic efficiency.

Recent Development of Active Ingredients in Mouthwashes and Toothpastes for Periodontal Diseases.

Periodontal diseases like gingivitis and periodontitis are primarily caused by dental plaque. Several antiplaque and anti-microbial agents have been successfully incorporated into toothpastes and mouthwashes to control plaque biofilms and to prevent and treat gingivitis and periodontitis. The aim of this article was to review recent developments in the antiplaque, anti-gingivitis, and anti-periodontitis properties of some common compounds in toothpastes and mouthwashes by evaluating basic and clinical studies, especially the ones published in the past five years. The common active ingredients in toothpastes and mouthwashes included in this review are chlorhexidine, cetylpyridinium chloride, sodium fluoride, stannous fluoride, stannous chloride, zinc oxide, zinc chloride, and two herbs-licorice and curcumin. We believe this comprehensive review will provide useful up-to-date information for dental care professionals and the general public regarding the major oral care products on the market that are in daily use.

Enhanced Biofilm Eradication and Reduced Cytotoxicity of a Novel Polygalacturonic and Caprylic Acid Wound Ointment Compared with Common Antiseptic Ointments.

Antiseptic wound ointments are widely used to treat dermal wounds that are microbially contaminated. Polygalacturonic acid (PG)+caprylic acid (CAP) is a novel combination that has been shown to eradicate biofilms. We developed a novel PG+CAP ointment and compared the biofilm eradication capability and cytotoxicity of PG+CAP with that of commercially available antiseptic wound ointments. We used a well-established biofilm model to quantitatively assess the eradication of organisms following exposure to the wound ointments for 2 hours. PG+CAP ointment completely eradicated Candida albicans, multidrug-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus biofilms, whereas MediHoney, polyhexamethylene biguanide (PHMB), and benzalkonium chloride (BZK) ointments failed to eradicate all biofilms within 2 hours. We assessed cytotoxicity by exposing L-929 fibroblasts to extracts of each ointment; Trypan blue exclusion was used to assess cell viability, and Alamar blue conversion was used to assess metabolic function. After exposure to PG+CAP and MediHoney, fibroblast viability was 96.23% and 95.23%, respectively (Trypan blue), and was comparable to untreated cells (98.77%). PHMB and BZK showed reduced viability (83.25% and 77.83%, respectively, p < 0.05). Metabolic activity results followed a similar pattern. Cytotoxicity of PG+CAP ointment towards erythrocytes was comparable to saline. PG+CAP ointment seems to be safe and can rapidly eradicate microbial biofilm; thus, PG+CAP ointment merits further in vivo testing as a potential antimicrobial wound ointment.

Formulation Development of Topical Preparation Containing Nanoparticles of Povidone-Iodine for Wound Healing.

Povidone-iodine (PVI) is an antiseptic drug that is used for wound healing or for repair of the damaged tissue. Studies on solid lipid nanoparticles (SLNs) indicate that this system could potentially be used as a delivery system with improved drug entrapment efficiency and controlled drug release for hydrophilic actives. This study focuses on developing a topical gel containing SLNs of PVI for wound healing. SLNs were prepared by using the solvent emulsification diffusion method. Lipids such as glycerol monostearate, palmitic acid, and stearic acid, and surfactants such as polysorbate 80, soyalecithin, and Pluronic F-68 were used for the preparation of SLN. These were screened out based on particle size and entrapment efficiency of SLN. Gel was prepared by using Carbopol 940 (1% w/w) and propylene glycol (10% w/w). Formulated SLNs were evaluated by various in vitro and in vivo techniques. Based on the results, the drug-to-lipid ratio (1:3) and 2% polysorbate 80 (surfactant) along with stirring rate (3,000 rpm) produced the desired particle size (285.4 nm) with good stability. 22.85% drug loading and 88.83% drug entrapment efficiency were found in the optimized formulation. In vitro drug release shows that it follows the Korsmeyer-Peppas model. The animal study shows that the period of epithelization produced by the test group was 17.14 ± 1.35 days, which was near to that of the standard group (16.25 ± 1.24 days). Clinical Trial Registration number: 1044/PO/Re/S/07/CPCSEA.

Allergenic Ingredients in Health Care Hand Sanitizers in the United States.

BACKGROUND: Health care workers with occupational contact dermatitis often attribute their symptoms to frequent use of alcohol-based hand sanitizers. However, ingredient lists are difficult to obtain, and safe alternatives typically must accommodate brands utilized by a particular hospital system. OBJECTIVE: The aims of this study were to investigate allergenic ingredients present within health care hand sanitizers and to provide a comprehensive product list to assist with allergen avoidance. METHODS: Five major hospitals in Minnesota and 20 hospitals across the United States were called to obtain a product list. The National Library of Medicine's DailyMed Web site was searched to retrieve ingredients. Ingredients were compared with the American Contact Dermatitis Society 2017 Core Allergen Series and cross-reactors. RESULTS: The most common brands included Purell, Ecolab, DebMed, and Avagard. Active ingredients consisted of ethyl alcohol (85.0%), benzalkonium chloride (8.8%), or isopropyl alcohol (2.5%). Top 5 allergens included tocopherol (51.3%), fragrance (40.0%), propylene glycol (27.5%), benzoates (25.0%), and cetyl stearyl alcohol (12.5%). Four sanitizers were free of all American Contact Dermatitis Society allergens; 15 products contained only tocopherol or propylene glycol as allergens. CONCLUSIONS: We identified 19 low-allergen hand sanitizers within the most common brands utilized by US hospital systems. This product list will be useful for patients and health care workers seeking allergen avoidance.

Alcohol-free hand sanitizer and other quaternary ammonium disinfectants quickly and effectively inactivate SARS-CoV-2.

BACKGROUND: SARS-CoV-2 is the virus responsible for the current global pandemic, COVID-19. Because this virus is novel, little is known about its sensitivity to disinfection. METHODS: We performed suspension tests against SARS-CoV-2 using three commercially available quaternary ammonium compound (Quat) disinfectants and one laboratory-made 0.2% benzalkonium chloride solution. FINDINGS: Three of the four formulations completely inactivated the virus within 15 s of contact, even in the presence of a soil load or when diluted in hard water. CONCLUSION: Quats rapidly inactivate SARS-CoV-2, making them potentially useful for controlling SARS-CoV-2 spread in hospitals and the community.

Water-Repellent TiO2-Organic Dye-Based Air Filters for Efficient Visible-Light-Activated Photochemical Inactivation against Bioaerosols.

Recently, bioaerosols, including the 2019 novel coronavirus, pose a serious threat to global public health. Herein, we introduce a visible-light-activated (VLA) antimicrobial air filter functionalized with titanium dioxide (TiO2)-crystal violet (CV) nanocomposites facilitating abandoned visible light from sunlight or indoor lights. The TiO2-CV based VLA antimicrobial air filters exhibit a potent inactivation rate of ∼99.98% and filtration efficiency of ∼99.9% against various bioaerosols. Under visible-light, the CV is involved in overall inactivation by inducing reactive oxygen species production both directly (CV itself) and indirectly (in combination with TiO2). Moreover, the susceptibility of the CV to humidity was significantly improved by forming a hydrophobic molecular layer on the TiO2 surface, highlighting its potential applicability in real environments such as exhaled or humid air. We believe this work can open a new avenue for designing and realizing practical antimicrobial technology using ubiquitous visible-light energy against the threat of infectious bioaerosols.

Bacterial Biofilms on Polyamide Nanofibers: Factors Influencing Biofilm Formation and Evaluation.

Electrospun polyamide (PA) nanofibers have great potential for medical applications (in dermatology as antimicrobial compound carriers or surgical sutures). However, little is known about microbial colonization on these materials. Suitable methods need to be chosen and optimized for the analysis of biofilms formed on nanofibers and the influence of their morphology on biofilm formation. We analyzed 11 PA nanomaterials, both nonfunctionalized and functionalized with AgNO3, and tested the formation of a biofilm by clinically relevant bacteria (Escherichia coli CCM 4517, Staphylococcus aureus CCM 3953, and Staphylococcus epidermidis CCM 4418). By four different methods, it was confirmed that all of these bacteria attached to the PAs and formed biofilms; however, it was found that the selected method can influence the outcomes. For studying biofilms formed by the selected bacteria, scanning electron microscopy, resazurin staining, and colony-forming unit enumeration provided appropriate and comparable results. The values obtained by crystal violet (CV) staining were misleading due to the binding of the CV dye to the PA structure. In addition, the effect of nanofiber morphology parameters (fiber diameter and air permeability) and AgNO3 functionalization significantly influenced biofilm maturation. Furthermore, the correlations between air permeability and surface density and fiber diameter were revealed. Based on the statistical analysis, fiber diameter was confirmed as a crucial factor influencing biofilm formation (p ≤ 0.01). The functionalization of PAs with AgNO3 (from 0.1 wt %) effectively suppressed biofilm formation. The PA functionalized with a concentration of 0.1 wt % AgNO3 influenced the biofilm equally as nonfunctionalized PA 8% 2 g/m2. Therefore, biofilm formation could be affected by the above-mentioned morphology parameters, and ultimately, the risk of infections from contaminated medical devices could be reduced.

Prediction of the skin sensitization potential of polyhexamethylene guanidine and triclosan and mixtures of these compounds with the excipient propylene glycol through the human Cell Line Activation Test.

Household products often contain an antimicrobial agent such as biocides, polyhexamethylene guanidine (PHMG), triclosan (TCS), and propylene glycol (PG) as an excipient to dissolve the active ingredients. The skin sensitization (SS) potentials of each of these substances or mixtures of PHMG or TCS with PG have not been investigated through in vitro alternative test methods. The in vitro alternative assay called human Cell Line Activation Test (h-CLAT) served to address these issues. The h-CLAT assay was conducted in accordance with OECD TG 442E. On three independent runs, all the three substances were predicted to be sensitizers according to the SS positivity with relative fluorescence intensity of CD86 ≥ 150% and/or CD54 ≥ 200% at any tested concentrations. Mixtures of PHMG or TCS with PG at ratios of 9:1, 4:1, or 1:4 weight/volume were all positive in terms of SS potential. Since humans can be occupationally or environmentally exposed to mixtures of excipients with active ingredients of biocides, the present study may give insights into further investigations of the SS potentials of various chemical mixtures.

Changes in workflow to a University Pharmacy to facilitate compounding and distribution of antiseptics for use against COVID-19.

This article is a report from an experience about a work developed by Farmácia Universitária at UFRJ (FU-UFRJ) during the nCov-19 pandemic period. The aim of this work was to describe its contribution in the production of antiseptic supplies used to prevent contagion by the new coronavirus. The work routine at the pharmacy has been changed to allow the implementation of local workflow during the pandemic, and to adapt the protection rules to meet the safety measures. FU-UFRJ started to manipulate two antiseptic formulations: 70% ethyl alcohol and gel alcohol, which are included in the National Form, manufacturing around 100 L of these formulations, weekly, to donate to different health units. The experience enabled the adaptation to emergency health standards, planning and meaningful guidance to pharmacists and technicians to attend clinics at university hospitals, vaccination center and UFRJ city hall, in order to facilitate the access to adequate hand hygiene to the population.