A novel long-acting antimicrobial nanomicelle spray.

Contaminated surfaces play a major role in disease transmission to humans. The vast majority of commercial disinfectants provide short-term protection of surfaces against microbial contamination. The Covid-19 pandemic has attracted attention to the importance of long-term disinfectants as they would reduce the need for staff and save time. In this study, nanoemulsions and nanomicelles containing a combination of benzalkonium chloride (BKC; a potent disinfectant and a surfactant) and benzoyl peroxide (BPO; a stable form of peroxide that is activated upon contact with lipid/membranous material) were formulated. The prepared nanoemulsion and nanomicelle formulas were of small sizes <80 nm and high positive charge >45 mV. They showed enhanced stability and prolonged antimicrobial efficacy. The antibacterial potency was evaluated in terms of long-term disinfection on surfaces as verified by repeated bacterial inoculums. Additionally, the efficacy of killing bacteria upon contact was also investigated. A nanomicelle formula (NM-3) consisting of 0.8% BPO in acetone and 2% BKC plus 1% TX-100 in distilled water (1 : 5 volume ratio) demonstrated overall surface protection over a period of 7 weeks upon a single spray application. Furthermore, its antiviral activity was tested by the embryo chick development assay. The prepared NM-3 nanoformula spray showed strong antibacterial activities against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus as well as antiviral activities against infectious bronchitis virus due to the dual effects of BKC and BPO. The prepared NM-3 spray shows great potential as an effective solution for prolonged surface protection against multiple pathogens.

Toward Scaling up the Production of Metal Oxide Nanoparticles for Application on Washable Antimicrobial Cotton Fabrics.

To examine the utilization of metal oxide nanoparticles (NPs) in different commercial products, this work focuses on the determination of cost-effective and scalable synthesis protocols. The solvothermal protocol is well-known as a scalable method but has recently been shown to lack economic feasibility. The mechanochemical method has recently been recognized to be a more economic and environmentally friendly substitute for the solvothermal method. In this study, zinc oxide nanoparticles (ZnO NPs) and copper oxide nanoparticles (CuO NPs) were synthesized using two (aqueous and organic) solvothermal (wet) methods and two (manual and automated) mechanochemical (dry) methods. The four methods were evaluated and compared. The automated mechanochemical method generated a significantly higher yield of ZnO NPs (82%) and CuO NPs (84%) using the least energy and time. However, the prepared ZnO NPs displayed higher cytotoxicity against Vero E6 cells when compared to that of CuO NPs. Because of their low cytotoxicity, CuO NPs synthesized via the automated mechanochemical method were selected for application onto cotton fabrics. Lower cytotoxicity was observed for CuO NPs treated fabrics with an IC50 of 562 mg/mL and ZnO treated fabrics with an IC50 at 23.93 mg/mL when the treated fabrics were tested against L929 fibroblast cells. Additionally, the cotton fabrics retained bactericidal and virucidal effects after four washes. Thus, the current study recommends the automated mechanochemical method as a cost-effective scalable approach for the synthesis of CuO NPs. The application of CuO NPs onto cotton fabrics generated washable antimicrobial face masks.

Wet Electrospun Nanofibers-Fortified Gelatin/Alginate-Based Nanocomposite as a Single-Dose Biomimicking Skin Substitute.

We report the development and evaluation of a series of well-designed single-dose extracellular matrix (ECM)-mimicking nanofibers (NFs)-reinforced hydrogel (HG)-based skin substitute for wound healing. The HG matrix of the proposed skin substitute is composed of gelatin (GE) and sodium alginate (SA), and incorporates hyaluronic acid (HA) as a key component of the natural ECM, as well as the antimicrobial Punica granatum extract (PE). This HG nanocomposite was cross-linked by the biocompatible N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride (EDC) cross-linker, and was reinforced with fragmented trans-ferulic acid (FA)-loaded cellulose acetate/polycaprolactone (PCL/CA) NFs. The NFs were obtained via wet electrospinning into a poly(vinyl alcohol) (PVA) coagulating solution to closely resemble the porous structure of the ECM fibers, which facilitates cell migration, attachment, and proliferation. The proposed design of the skin substitute allows adjustable mechanical characteristics and outstanding physical properties (swelling and biodegradability), as well as an excellent porous microstructure. The developed skin substitutes were characterized using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and electron microscopy. In addition, the biodegradability, biocompatibility, bioactivity, mechanical, and in vitro drug release characteristics were investigated. Moreover, an in vivo excisional full-thickness defect model was conducted to assess skin regeneration and healing effectiveness. The average diameters of the plain and FA-loaded NFs are 210 ± 12 nm and 452 ± 25 nm, respectively. The developed ECM-mimicking skin substitutes demonstrated good antibacterial activity, free-radical scavenging activity, cytocompatibility, porosity, water absorption ability, and good biodegradability. In vivo application of the ECM-mimicking skin substitutes revealed their excellent wound-healing activity and their suitability for single-dose treatment of deep wounds with reducing the wound diameter to 0.95 mm after 15 days of treatment. Moreover, the histological investigation of the wound area demonstrated that the applied skin substitutes have not only enhanced the wound healing progress, but also can participate in improving the quality of the regenerated skin in the treated area via facilitating collagen fibers regeneration and deposition.

Multifunctional Hemostatic PVA/Chitosan Sponges Loaded with Hydroxyapatite and Ciprofloxacin.

The present study describes the development of multifunctional hemostatic sponges to control bleeding. Chitosan (Ch) and poly(vinyl alcohol) (PVA) were selected as the basic polymeric matrix [Ch/PVA] for sponges. Glycerol and citric acid were used as crosslinkers [Ch/PVA/G(Cl)] to enhance the mechanical properties of the developed sponges. Ciprofloxacin (AB) was added to the developed sponge to impart antibacterial activity. Hydroxyapatite (HA) was also added, which would make the sponge suitable for bone surgery. Among the developed sponges, the Ch/PVA/G(Cl)-HA-AB sponge demonstrated enhanced cell viability, mechanical properties, and strong antimicrobial effect against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, in addition to platelet aggregation activity. The addition of ciprofloxacin and hydroxyapatite promotes a unique synergistic effect of antimicrobial activity and hemostasis. Thus, the present study introduces Ch/PVA/G(Cl)-HA-AB, a multifunctional hemostatic sponge that would be suitable for bone surgical applications.

Development of a silk fibroin-based multitask aerosolized nanopowder formula for efficient wound healing.

Most of the spray products in the market for wound healing applications are loaded with antibiotics that exert their antibacterial effect within the inflammatory stage of wound healing without demonstrating any effect in the subsequent proliferation stage. This study introduces a new aerosolized nanopowder (ANP) formula that not only exhibits antibacterial effect but also antioxidant and enhanced cell proliferation effects. Within the introduced ANP formula, Avicenna marina (Am) extract and neomycin (NM) antibiotic have been loaded within silk-fibroin nanoparticles (FB NPs). The Am has been extracted via different solvent systems, and investigated for its antioxidant and antibacterial activity as well as its ability to enhance cell proliferation. The physicochemical properties, size, zeta-potential and morphology of the prepared Am/FB NPs, NM/FB NPs and ANP formula were investigated. Besides, the ANP formula exhibited good antibacterial activities against Staphylococcus aureus, Methicillin resistant S. aureus, Pseudomonas aeruginosa and Resistant P. aeruginosa. Scratch wound healing assay on human fibroblast monolayers demonstrated 100% wound closure after 24 h upon using the ANP formula as compared to 70% wound closure for positive control (NM). The wound healing ability of the ANP formula has been further confirmed by histopathological evaluation of the wound site and depicted a marked increase in fibroblast proliferation and reduction of inflammatory cells after 15 days with a complete wound closure as compared to controls. The obtained results prove the beneficial effects of the Am extract on wound healing and introduce the developed multitask nanopowder formula as a potential wound healing spray.

Metal nanoparticles fabricated by green chemistry using natural extracts: biosynthesis, mechanisms, and applications.

Nanoparticles (NPs) are new inspiring clinical targets that have emerged from persistent efforts with unique properties and diverse applications. However, the main methods currently utilized in their production are not environmentally friendly. With the aim of promoting a green approach for the synthesis of NPs, this review describes eco-friendly methods for the preparation of biogenic NPs and the known mechanisms for their biosynthesis. Natural plant extracts contain many different secondary metabolites and biomolecules, including flavonoids, alkaloids, terpenoids, phenolic compounds and enzymes. Secondary metabolites can enable the reduction of metal ions to NPs in eco-friendly one-step synthetic processes. Moreover, the green synthesis of NPs using plant extracts often obviates the need for stabilizing and capping agents and yields biologically active shape- and size-dependent products. Herein, we review the formation of metallic NPs induced by natural extracts and list the plant extracts used in the synthesis of NPs. In addition, the use of bacterial and fungal extracts in the synthesis of NPs is highlighted, and the parameters that influence the rate of particle production, size, and morphology are discussed. Finally, the importance and uniqueness of NP-based products are illustrated, and their commercial applications in various fields are briefly featured.

Apitherapeutics and phage-loaded nanofibers as wound dressings with enhanced wound healing and antibacterial activity.

AIM: Develop green wound dressings which exhibit enhanced wound-healing ability and potent antibacterial effects. METHODS: Honey, polyvinyl alcohol, chitosan nanofibers were electrospun and loaded with bee venom, propolis and/or bacteriophage against the multidrug-resistant Pseudomonas aeruginosa and examined for their antibacterial, wound-healing ability and cytotoxicity. RESULTS: Among different formulations of nanofibers, honey, polyvinyl alcohol, chitosan-bee venom/bacteriophage exhibited the most potent antibacterial activity against all tested bacterial strains (Gram-positive and -negative strains) and achieved nearly complete killing of multidrug-resistant P. aeruginosa. In vivo testing revealed enhanced wound-healing results and cytotoxicity testing proved improved biocompatibility. CONCLUSION: The developed biocompatible nanofibers represent competitive wound-healing dressings with potent antibacterial and wound-healing activity.

The effect of increasing honey concentration on the properties of the honey/polyvinyl alcohol/chitosan nanofibers.

The effect of increasing honey concentrations from 10% to 30% within the Honey (H)/polyvinyl alcohol (P)/chitosan (CS) nanofibers was investigated. Changes in the electrospun nanofiber diameters, crystallinity, thermal behavior, porosity and antibacterial activity have been assessed using SEM, XRD, DSC, TGA, mercury porosimeter and viable cell count technique. The HPCS nanofibers were cross-linked and tested for their swelling abilities and degradation behavior. The mean diameter of HPCS nanofibers increased from 284±97nm to 464±185nm upon increasing the honey concentration from 10% to 30%. Irrespective the honey concentrations, the nanofibers have demonstrated enhanced porosity. Increasing the honey concentration resulted in a reduction in the swelling of the 1h cross-linked HPCS nanofibers containing 10% and 30% H from 520% to 100%; respectively. Degradation after 30days was reduced in the 3h cross-linked HPCS nanofibers compared to the non-crosslinked HPCS nanofibers. Enhanced antibacterial activity was achieved against both Staphylococcus aureus and Escherichia coli upon increasing the honey concentration. Changing the honey concentration and the extent of nanofiber crosslinking can be used to adjust different parameters of the HPCS nanofibers to suit their applications in wound healing and tissue engineering.

Honey/Chitosan Nanofiber Wound Dressing Enriched with Allium sativum and Cleome droserifolia: Enhanced Antimicrobial and Wound Healing Activity.

Two natural extracts were loaded within fabricated honey, poly(vinyl alcohol), chitosan nanofibers (HPCS) to develop biocompatible antimicrobial nanofibrous wound dressing. The dried aqueous extract of Cleome droserifolia (CE) and Allium sativum aqueous extract (AE) and their combination were loaded within the HPCS nanofibers in the HPCS-CE, HPCS-AE, and HPCS-AE/CE nanofiber mats, respectively. It was observed that the addition of AE resulted in the least fiber diameter (145 nm), whereas the addition of the AE and CE combination resulted in the least swelling ability and the highest weight loss. In vitro antibacterial testing against Staphylococcus aureus, Escherichia coli, Methicillin-resistant S. aureus (MRSA), and multidrug-resistant Pseudomonas aeruginosa was performed in comparison with the commercial dressing AquacelAg and revealed that the HPCS-AE and HPCS-AE/CE nanofiber mats allowed complete inhibition of S. aureus and the HPCS-AE/CE exhibited mild antibacterial activity against MRSA. A preliminary in vivo study revealed that the developed nanofiber mats enhanced the wound healing process as compared to the untreated control as proved by the enhanced wound closure rates in mice and by the histological examination of the wounds. Moreover, comparison with the commercial dressing Aquacel Ag, the HPCS, and HPCS-AE/CE demonstrated similar effects on the wound healing process, whereas the HPCS/AE allowed an enhanced wound closure rate. Cell culture studies proved the biocompatibility of the developed nanofiber mats in comparison with the commercial Aquacel Ag, which exhibited noticeable cytotoxicity. The developed natural nanofiber mats hold potential as promising biocompatible antibacterial wound dressing.

High concentration honey chitosan electrospun nanofibers: biocompatibility and antibacterial effects.

Honey nanofibers represent an attractive formulation with unique medicinal and wound healing advantages. Nanofibers with honey concentrations of <10% were prepared, however, there is a need to prepare nanofibers with higher honey concentrations to increase the antibacterial and wound healing effects. In this work, chitosan and honey (H) were cospun with polyvinyl alcohol (P) allowing the fabrication of nanofibers with high honey concentrations up to 40% and high chitosan concentrations up to 5.5% of the total weight of the fibers using biocompatible solvents (1% acetic acid). The fabricated nanofibers were further chemically crosslinked, by exposure to glutaraldehyde vapor, and physically crosslinked by heating and freezing/thawing. The new HP-chitosan nanofibers showed pronounced antibacterial activity against Staphylococcus aureus but weak antibacterial activity against Escherichia coli. The developed HP-chitosan nanofibers revealed no cytotoxicity effects on cultured fibroblasts. In conclusion, biocompatible, antimicrobial crosslinked honey/polyvinyl alcohol/chitosan nanofibers were developed which hold potential as effective wound dressing.

Phage approved in food, why not as a therapeutic?

Bacterial resistance is not only restricted to human infections but is also a major problem in food. With the marked decrease in produced antimicrobials, the world is now reassessing bacteriophages. In 2006, ListShield™ received the US FDA approval for using phage in food. Nevertheless, regulatory approval of phage-based therapeutics is still facing many challenges. This review highlights the use of bacteriophages as biocontrol agents in the food industry. It also focuses on the challenges still facing the regulatory approval of phage-based therapeutics and the proposed approaches to overcome such challenges.