Protecting the Antibacterial Coating of Urinal Catheters for Improving Safety.

Catheter-associated urinary tract infections (CAUTI) are among the most common bacterial infections associated with prolonged hospitalization and increased healthcare expenditures. Despite recent advances in the prevention and treatment of these infections, there are still many challenges remaining, among them the creation of a durable catheter coating, which prevents bacterial biofilm formation. The current work reports on a method of protecting medical tubing endowed with antibiofilm properties. Silicone catheters coated sonochemically with ZnO nanoparticles (NPs) demonstrated excellent antibiofilm effects. Toward approval by the European Medicines Agency, it was realized that the ZnO coating would not withstand the regulatory requirements of avoiding dissolution for 14 days in artificial urine examination. Namely, after exposure to urine for 14 days, the coating amount was reduced by 90%. Additional coatings with either carbon or silica maintained antibiofilm activity against Staphylococcus aureus while resisting dissolution in artificial urine for 14 days (C- or SiO2-protected catheters exhibited only 29% reduction). HR-SEM images of the protected catheters indicate the presence of the ZnO coating as well as the protective layer. Antibiofilm activity of all catheters was evaluated both before and after exposure to artificial urine. It was shown that before artificial urine exposure, all coated catheters showed high antibiofilm properties compared to the uncoated control. Exposure of ZnO-coated catheters, without the protective layer, to artificial urine had a significant effect exhibited by the decrease in antibiofilm activity by almost 2 orders of magnitude, compared to unexposed catheters. Toxicity studies performed using a reconstructed human epidermis demonstrated the safety of the improved coating. Exposure of the epidermis to ZnO catheter extracts in artificial urine affects tissue viability compared with control samples, which was not observed in the case of ZnO NPs coating with SiO2 or C. We suggest that silica and carbon coatings confer some protection against zinc ions release, improving ZnO coating safety.

Comparative Analysis of the Efficacy of Different Regimens of 12 Months Rifaximin-Alfa Therapy in Patients with Liver Cirrhosis and Minimal Hepatic Encephalopathy.

It is a matter of current interest which rifaximin-α regimens in patients with liver cirrhosis and minimal hepatic encephalopathy are the most efficient. STUDY OBJECTIVE: to evaluate the effect of various rifaximin-α regimens for 12 months on clinical and laboratory parameters and quality of life in patients with liver cirrhosis and minimal hepatic encephalopathy. METHODS: It was a multicenter, prospective, open-label, observational study that included 288 patients with liver cirrhosis and minimal hepatic encephalopathy of both sexes over the age of 18 years, who were prescribed a 12-month course of treatment with rifaximin-α in accordance with the product label. Statistical analysis was performed in the population of patients who completed all visits according to the protocol (n = 258). Retrospectively, the patients were divided into two subgroups: subgroup 1 (continuous course)-patients who received the study drug for a year and the number of days of administration was 360 days (n = 41); subgroup 2 (cyclic course)-patients who received the study drug during the year for less than 360 days (n = 217). At each of the 4 visits, the quality of life was assessed using the CLDQ questionnaire, the time to perform the number connection test, the severity of symptoms associated with hepatic encephalopathy, and laboratory parameters. RESULTS: During the 12-month observation period, an increase in the total score on the CLDQ quality of life questionnaire in patients with chronic liver diseases was revealed, which indicates an improvement in the quality of life of patients receiving rifaximin-α therapy. When patients were divided into subgroups depending on the duration of therapy, some benefits of continuous rifaximin-α therapy were noted in the more pronounced dynamics of decrease in the time to perform the number connection test, and in decreased severity of the following symptoms associated with hepatic encephalopathy: impaired concentration and memory, cognitive impairment, and decreased performance. Laboratory findings showed positive dynamics in both subgroups. CONCLUSION: A continuous rifaximin-α regimen in patients with liver cirrhosis and minimal hepatic encephalopathy for 12 months was superior to cyclic use with a more pronounced effect on the quality of life of patients and on the symptoms associated with hepatic encephalopathy.

Multimodal silver-chitosan-acylase nanoparticles inhibit bacterial growth and biofilm formation by Gram-negative Pseudomonas aeruginosa bacterium.

Pseudomonas aeruginosa bacteria originate severe infections in hospitalized patients and those with chronic debilitating diseases leading to increased morbidity and mortality, longer hospitalization and huge financial burden to the healthcare system. The clinical relevance of P. aeruginosa infections is increased by the capability of this bacterium to grow in biofilms and develop multidrug resistant mechanisms that preclude conventional antibiotic treatments. Herein, we engineered novel multimodal nanocomposites that integrate in the same entity antimicrobial silver nanoparticles (NPs), the intrinsically antimicrobial, but biocompatible biopolymer chitosan, and the anti-infective quorum quenching enzyme acylase I. Acylase present in the NPs specifically degraded the signal molecules governing bacterial cell-to-cell communication and inhibited by âˆ¼ 55 % P. aeruginosa biofilm formation, while the silver/chitosan template altered the integrity of bacterial membrane, leading to complete eradication of planktonic bacteria. The innovative combination of multiple bacteria targeting modalities resulted in 100-fold synergistic enhancement of the antimicrobial efficacy of the nanocomposite at lower and non-hazardous towards human skin cells concentrations, compared to the silver/chitosan NPs alone.

Bio-Based Nano-Enabled Cosmetic Formulations for the Treatment of Cutibacterium acnes-Associated Skin Infections.

Acne is a common chronic skin condition with serious physical and psychosocial consequences. In some cases, the appearance of pimples, whiteheads, or blackheads on the face, neck, and back may lead to scarring, disfiguring, depression, frustration, and anxiety in patients. Current treatments rely on antibiotics to eradicate Cutibacterium acnes (C. acnes), the bacterium responsible for this skin condition. However, these approaches do not scavenge the reactive oxidative species (ROS) generated during disease development and raise concerns about the increase in antimicrobial resistance. In this study, an environmentally friendly and cost-effective self-assembly nanoencapsulation technology based on zein, a bio-based hydrophobic protein, was employed to produce multifunctional essential oil (EO)-loaded nanocapsules (NCs) with superior antioxidant and bactericidal activity toward C. acnes. The NCs displayed "smart" release of the active cargo only under the conditions that were conducive to acne proliferation on skin. Once incorporated into creams, the EO-loaded NCs led to a complete inhibition of C. acnes and demonstrated the capacity to scavenge ROS, thus preventing damage to human skin cells. The in vitro permeation studies revealed that the nanoformulated EO was able to penetrate through the epidermis, indicating its potential for the treatment of skin diseases, such as acne.

Nanomaterials and Coatings for Managing Antibiotic-Resistant Biofilms.

Biofilms are a global health concern responsible for 65 to 80% of the total number of acute and persistent nosocomial infections, which lead to prolonged hospitalization and a huge economic burden to the healthcare systems. Biofilms are organized assemblages of surface-bound cells, which are enclosed in a self-produced extracellular polymer matrix (EPM) of polysaccharides, nucleic acids, lipids, and proteins. The EPM holds the pathogens together and provides a functional environment, enabling adhesion to living and non-living surfaces, mechanical stability, next to enhanced tolerance to host immune responses and conventional antibiotics compared to free-floating cells. Furthermore, the close proximity of cells in biofilms facilitates the horizontal transfer of genes, which is responsible for the development of antibiotic resistance. Given the growing number and impact of resistant bacteria, there is an urgent need to design novel strategies in order to outsmart bacterial evolutionary mechanisms. Antibiotic-free approaches that attenuate virulence through interruption of quorum sensing, prevent adhesion via EPM degradation, or kill pathogens by novel mechanisms that are less likely to cause resistance have gained considerable attention in the war against biofilm infections. Thereby, nanoformulation offers significant advantages due to the enhanced antibacterial efficacy and better penetration into the biofilm compared to bulk therapeutics of the same composition. This review highlights the latest developments in the field of nanoformulated quorum-quenching actives, antiadhesives, and bactericides, and their use as colloid suspensions and coatings on medical devices to reduce the incidence of biofilm-related infections.

Ionic Liquids as Biocompatible Antibacterial Agents: A Case Study on Structure-Related Bioactivity on Escherichia coli.

The potential of ionic liquids (ILs) to be used as antimicrobial agents for biomedical applications has been hindered by the fact that most of them are cytotoxic toward mammalian cells. Understanding the mechanism of bacterial and mammalian cellular damage of ILs is key to their safety design. In this work, we evaluate the antimicrobial activity and mode of action of several ILs with varying anions and cations toward the clinically relevant Gram-negative Escherichia coli. Langmuir monolayer technique was used to evaluate if the IL's mode of action was related to the bacterial cell membrane interaction for an effective E. coli killing. 1-Decyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide [DMIM][TFSI] and trihexyltetradecyl phosphonium bis(trifluoromethylsulfonyl) imide [P6,6,6,14][TFSI] were surface-active and induced bacterial cell lysis, through a membrane-disruption phenomenon on bacteria, in a mechanism that was clearly related to the long alkyl chains of the cation. 1-Ethyl-3-methylimidazolium hydrogen sulfate [EMIM][HSO4] was highly antimicrobial toward E. coli and found suitable for biological applications since it was harmless to mammalian cells at most of the tested concentrations. The results suggest that the imidazolium cation of the ILs is mostly responsible not only for their antimicrobial activity but also for their cytotoxicity, and the inclusion of different anions may tailor the ILs' biocompatibility without losing the capacity to kill bacteria, as is the case of [EMIM][HSO4]. Importantly, this IL was found to be highly antimicrobial even when incorporated in a polymeric matrix.

Sono-Enzymatically Embedded Antibacterial Silver-Lignin Nanoparticles on Cork Filter Material for Water Disinfection.

Providing clean drinking water is a great challenge worldwide, especially for low-income countries where the access to safe water is limited. During the last decade, new biotechnological approaches have been explored to improve water management. Among them, the use of antimicrobial nanoparticles for designing innovative centralized and decentralized (point-of-use) water treatment systems for microbial decontamination has received considerable attention. Herein, antimicrobial lignin capped silver nanoparticles (AgLNP) were embedded on residual cork pieces using high-intensity ultrasound coupled with laccase-mediated grafting to obtain biofunctionalized nanomaterial. The developed AgLNP-coated cork proved to be highly efficient to drastically reduce the number of viable Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus in liquid medium. Additionally, the coated-cork was characterized using FTIR-ATR spectroscopy and SEM imaging, and further used as a filter bed in a point-of-use device for water disinfection. The constructed water filtering system significantly reduced the amount of viable E. coli and resistant Bacillus cereus spores from filtered water operating at increasing residence times of 1, 4, 6, 16, 24, and 48 h. Therefore, the presented results prove that the obtained cork-based antimicrobial nanocomposite material could be used as a filtering medium for the development of water filtration system to control pathogen dissemination.

Antibacterial, Antibiofilm, and Antiviral Farnesol-Containing Nanoparticles Prevent Staphylococcus aureus from Drug Resistance Development.

Multidrug antimicrobial resistance is a constantly growing health care issue associated with increased mortality and morbidity, and huge financial burden. Bacteria frequently form biofilm communities responsible for numerous persistent infections resistant to conventional antibiotics. Herein, novel nanoparticles (NPs) loaded with the natural bactericide farnesol (FSL NPs) are generated using high-intensity ultrasound. The nanoformulation of farnesol improved its antibacterial properties and demonstrated complete eradication of Staphylococcus aureus within less than 3 h, without inducing resistance development, and was able to 100% inhibit the establishment of a drug-resistant S. aureus biofilm. These antibiotic-free nano-antimicrobials also reduced the mature biofilm at a very low concentration of the active agent. In addition to the outstanding antibacterial properties, the engineered nano-entities demonstrated strong antiviral properties and inhibited the spike proteins of SARS-CoV-2 by up to 83%. The novel FSL NPs did not cause skin tissue irritation and did not induce the secretion of anti-inflammatory cytokines in a 3D skin tissue model. These results support the potential of these bio-based nano-actives to replace the existing antibiotics and they may be used for the development of topical pharmaceutic products for controlling microbial skin infections, without inducing resistance development.

Nano-Formulation Endows Quorum Quenching Enzyme-Antibiotic Hybrids with Improved Antibacterial and Antibiofilm Activities against Pseudomonas aeruginosa.

The emergence of antibiotic resistant bacteria coupled with the shortage of efficient antibacterials is one of the most serious unresolved problems for modern medicine. In this study, the nano-hybridization of the clinically relevant antibiotic, gentamicin, with the bacterial pro-pathological cell-to-cell communication-quenching enzyme, acylase, is innovatively employed to increase its antimicrobial efficiency against Pseudomonas aeruginosa planktonic cells and biofilms. The sonochemically generated hybrid gentamicin/acylase nano-spheres (GeN_AC NSs) showed a 16-fold improved bactericidal activity when compared with the antibiotic in bulk form, due to the enhanced physical interaction and disruption of the P. aeruginosa cell membrane. The nano-hybrids attenuated 97 ± 1.8% of the quorum sensing-regulated virulence factors' production and inhibited the bacterium biofilm formation in an eight-fold lower concentration than the stand-alone gentamicin NSs. The P. aeruginosa sensitivity to GeN_AC NSs was also confirmed in a real time assay monitoring the bacterial cells elimination, using a quartz crystal microbalance with dissipation. In protein-enriched conditions mimicking the in vivo application, these hybrid nano-antibacterials maintained their antibacterial and antibiofilm effectiveness at concentrations innocuous to human cells. Therefore, the novel GeN_AC NSs with complementary modes of action show potential for the treatment of P. aeruginosa biofilm infections at a reduced antibiotic dosage.

Sonochemically engineered nano-enabled zinc oxide/amylase coatings prevent the occurrence of catheter-associated urinary tract infections.

Catheter-associated urinary tract infections (CAUTIs), caused by biofilms, are the most frequent health-care associated infections. Novel antibiofilm coatings are needed to increase the urinary catheters' life-span, decrease the prevalence of CAUTIs and reduce the development of antimicrobial resistance. Herein, antibacterial zinc oxide nanoparticles (ZnO NPs) were decorated with a biofilm matrix-degrading enzyme amylase (AM) and simultaneously deposited onto silicone urinary catheters in a one-step sonochemical process. The obtained nano-enabled coatings inhibited the biofilm formation of Escherichia coli and Staphylococcus aureus by 80% and 60%, respectively, for up to 7 days in vitro in a model of catheterized bladder with recirculation of artificial urine due to the complementary mode of antibacterial and antibiofilm action provided by the NPs and the enzyme. Over this period, the coatings did not induce toxicity to mammalian cell lines. In vivo, the nano-engineered ZnO@AM coated catheters demonstrated lower incidence of bacteriuria and prevent the early onset of CAUTIs in a rabbit model, compared to the animals treated with pristine silicone devices. The nano-functionalization of catheters with hybrid ZnO@AM coatings appears as a promising strategy for prevention and control of CAUTIs in the clinic.

Simultaneous Ultrasound-Assisted Hybrid Polyzwitterion/Antimicrobial Peptide Nanoparticles Synthesis and Deposition on Silicone Urinary Catheters for Prevention of Biofilm-Associated Infections.

Nosocomial infections caused by antibiotic-resistant bacteria are constantly growing healthcare threats, as they are the reason for the increased mortality, morbidity, and considerable financial burden due to the poor infection outcomes. Indwelling medical devices, such as urinary catheters, are frequently colonized by bacteria in the form of biofilms that cause dysfunction of the device and severe chronic infections. The current treatment strategies of such device-associated infections are impaired by the resistant pathogens but also by a risk of prompting the appearance of new antibiotic-resistant bacterial mechanisms. Herein, the one-step sonochemical synthesis of hybrid poly(sulfobetaine) methacrylate/Polymyxin B nanoparticles (pSBMA@PM NPs) coating was employed to engineer novel nanoenabled silicone catheters with improved antifouling, antibacterial, and antibiofilm efficiencies. The synergistic mode of action of nanohybridized zwitterionic polymer and antimicrobial peptide led to complete inhibition of the nonspecific protein adsorption and up to 97% reduction in Pseudomonas aeruginosa biofilm formation, in comparison with the pristine silicone. Additionally, the bactericidal activity in the hybrid coating reduced the free-floating and surface-attached bacterial growth by 8 logs, minimizing the probability for further P. aeruginosa spreading and host invasion. This coating was stable for up to 7 days under conditions simulating the real scenario of catheter usage and inhibited by 80% P. aeruginosa biofilms. For the same time of use, the pSBMA@PM NPs coating did not affect the metabolic activity and morphology of mammalian cells, demonstrating their capacity to control antibiotic-resistant biofilm-associated bacterial infections.

Targeting Intracellular Mycobacteria Using Nanosized Niosomes Loaded with Antibacterial Agents.

BACKGROUND: Pathogenic intracellular mycobacteria are challenging to treat because of the waxy and complex cell wall characterizing the genus. Niosomes are vesicles with biomimetic cell membrane composition, which allow them to efficiently bind to the eukaryotic cells and deliver their cargo into the cytoplasm. The objective of this study was to develop a new platform based on niosomes loaded with antimicrobial agents to target intracellular mycobacteria. Nanoniosomes were fabricated and loaded with antibiotics and lignin-silver nanoparticles. The efficacy of these nanoniosomes was tested against the intracellular pathogen Mycobacterium abscessus used as a model of infection of human-derived macrophages (THP-1). The cytotoxicity and the immunological response of the agents were tested on THP-1 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the secretion of pro- and anti-inflammatory cytokines, respectively. RESULTS: M. abscessus was susceptible to the nanoniosomes in infected THP-1 macrophages, suggesting that the nanoniosomes were internalized due to their fusion to the macrophage cellular membrane. Moreover, nanoniosomes showed no upregulation of pro-inflammatory cytokines when exposed to THP-1 macrophages. CONCLUSIONS: Nanoniosomes improved drug efficacy while decreasing toxicity and should be considered for further testing in the treatment of intracellular pathogenic mycobacteria or as a new platform for precise intracellular delivery of drugs.

Nanoparticle-driven self-assembling injectable hydrogels provide a multi-factorial approach for chronic wound treatment.

Chronic wounds represent a major health burden and drain on medical system. Efficient wound repair is only possible if the dressing materials target simultaneously multiple factors involved in wound chronicity, such as deleterious proteolytic and oxidative enzymes and high bacterial load. Here we develop multifunctional hydrogels for chronic wound management through self-assembling of thiolated hyaluronic acid (HA-SH) and bioactive silver-lignin nanoparticles (Ag@Lig NPs). Dynamic and reversible interactions between the polymer and Ag@Lig NPs yield hybrid nanocomposite hydrogels with shear-thinning and self-healing properties, coupled to zero-order kinetics release of antimicrobial silver in response to infection-related hyalurodinase. The hydrogels inhibit the major enzymes myeloperoxidase and matrix metalloproteinases responsible for wound chronicity in a patient's wound exudate. Furthermore, the lignin-capped AgNPs provide the hydrogel with antioxidant properties and strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The nanocomposite hydrogels are not toxic to human keratinocytes after 7 days of direct contact. Complete tissue remodeling and restoration of skin integrity is demonstrated in vivo in a diabetic mouse model. Hematological analysis reveals lack of wound inflammation due to bacterial infection or toxicity, confirming the potential of HA-SH/Ag@Lig NPs hydrogels for chronic wound management. STATEMENT OF SIGNIFICANCE: Multifunctional hydrogels are promising materials to promote healing of complex wounds. Herein, we report simple and versatile route to prepare biocompatible and multifunctional self-assembled hydrogels for efficient chronic wound treatment utilizing polymer-nanoparticle interactions. Hybrid silver-lignin nanoparticles (Ag@Lig NPs) played both: i) structural role, acting as crosslinking nodes in the hydrogel and endowing it with shear-thinning (ability to flow under applied shear stress) and self-healing properties, and ii) functional role, imparting strong antibacterial and antioxidant activity. Remarkably, the in situ self-assembling of thiolated hyaluronic acid and Ag@Lig NPs yields nanocomposite hydrogels able to simultaneously inhibits the major factors involved in wound chronicity, namely the overexpressed deleterious proteolytic and oxidative enzymes, and high bacterial load.

Novel Lignin-Capped Silver Nanoparticles against Multidrug-Resistant Bacteria.

The emergence of bacteria resistant to antibiotics and the resulting infections are increasingly becoming a public health issue. Multidrug-resistant (MDR) bacteria are responsible for infections leading to increased morbidity and mortality in hospitals, prolonged time of hospitalization, and additional burden to financial costs. Therefore, there is an urgent need for novel antibacterial agents that will both treat MDR infections and outsmart the bacterial evolutionary mechanisms, preventing further resistance development. In this study, a green synthesis employing nontoxic lignin as both reducing and capping agents was adopted to formulate stable and biocompatible silver-lignin nanoparticles (NPs) exhibiting antibacterial activity. The resulting silver-lignin NPs were approximately 20 nm in diameter and did not agglomerate after one year of storage at 4 °C. They were able to inhibit the growth of a panel of MDR clinical isolates, including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii, at concentrations that did not affect the viability of a monocyte-derived THP-1 human cell line. Furthermore, the exposure of silver-lignin NPs to the THP-1 cells led to a significant increase in the secretion of the anti-inflammatory cytokine IL-10, demonstrating the potential of these particles to act as an antimicrobial and anti-inflammatory agent simultaneously. P. aeruginosa genes linked with efflux, heavy metal resistance, capsular biosynthesis, and quorum sensing were investigated for changes in gene expression upon sublethal exposure to the silver-lignin NPs. Genes encoding for membrane proteins with an efflux function were upregulated. However, all other genes were membrane proteins that did not efflux metals and were downregulated.

Sonochemical coating of Prussian Blue for the production of smart bacterial-sensing hospital textiles.

In healthcare facilities, environmental microbes are responsible for numerous infections leading to patient's health complications and even death. The detection of the pathogens present on contaminated surfaces is crucial, although not always possible with current microbial detection technologies requiring sample collection and transfer to the laboratory. Based on a simple sonochemical coating process, smart hospital fabrics with the capacity to detect live bacteria by a simple change of colour are presented here. Prussian Blue nanoparticles (PB-NPs) are sonochemically coated on polyester-cotton textiles in a single-step requiring 15 min. The presence of PB-NPs confers the textile with an intensive blue colour and with bacterial-sensing capacity. Live bacteria in the textile metabolize PB-NPs and reduce them to colourless Prussian White (PW), enabling in situ detection of bacterial presence in less than 6 h with the bare eye (complete colour change requires 40 h). The smart textile is sensitive to both Gram-positive and Gram-negative bacteria, responsible for most nosocomial infections. The redox reaction is completely reversible and the textile recovers its initial blue colour by re-oxidation with environmental oxygen, enabling its re-use. Due to its simplicity and versatility, the current technology can be employed in different types of materials for control and prevention of microbial infections in hospitals, industries, schools and at home.

Antibody-Enabled Antimicrobial Nanocapsules for Selective Elimination of Staphylococcus aureus.

Targeted bactericide nanosystems hold significant promise to improve the efficacy of existing antimicrobials for treatment of severe bacterial infections, minimizing the side effects and lowering the risk of the development of antibiotic resistance. In this work, we developed antibody-functionalized nanocapsules (NCs) containing antibacterial essential oil (EO) for selective and effective eradication of Staphylococcus aureus. Antibacterial EO NCs were produced via self-assembly nanoencapsulation in the plant-derived protein zein. The obtained EO NCs were decorated with aminocellulose to provide more reactive surface groups for carboxyl-to-amine immobilization of a antibody that is specific against S. aureus. The antibody-enabled EO NCs (Ab@EO NCs) demonstrated 2-fold higher bactericidal efficacy against the targeted bacterium compared to the pristine EO NCs at the same concentrations. The improved antibacterial effect of the Ab@EO NCs toward S. aureus was also confirmed in a real-time assay by monitoring bacterial cells elimination using a quartz crystal microbalance. Furthermore, the Ab@EO NCs selectively decreased the load and changed the cell morphology of the targeted S. aureus in a mixed inoculum with nontargeted Pseudomonas aeruginosa. Applying the nanoformulated antibacterial actives to an in vitro coculture model of the bacteria and skin fibroblasts resulted in suppression of S. aureus growth while preserving the human cells viability. The novel antibody-enabled antibacterial NCs showed potential for improving the treatment efficacy of staphylococcal infections, minimally affecting the beneficial microbial and human cells.

Interaction of Silver-Lignin Nanoparticles With Mammalian Mimetic Membranes.

Silver nanoparticles (AgNPs) have broad spectrum antibacterial activity, but their toxicity to human cells has raised concerns related to their use as disinfectants or coatings of medically relevant surfaces. To address this issue, NPs comprising intrinsically bactericidal and biocompatible biopolymer and Ag with high antibacterial efficacy against common pathogens and compatibility to human cells have been engineered. However, the reason for their lower toxicity compared to AgNPs has not yet been elucidated. This work studies the in vitro interaction of AgLNPs with model mammalian membranes through two approaches: (i) Langmuir films and (ii) supported planar bilayers studied by quartz crystal microbalance and atomic force spectroscopy. These approaches elucidate the interactions of AgLNPs with the model membranes indicating a prominent effect of the bioresourced lignin to facilitate the binding of AgLNPs to the mammalian membrane, without penetrating through it. This study opens a new avenue for engineering of hybrid antimicrobial biopolymer - Ag or other metal NPs with improved bactericidal effect whereas maintaining good biocompatibility.

Electrical Evaluation of Bacterial Virulence Factors Using Nanopores.

In this work, we propose a novel methodology for electrical monitoring using nanoporous alumina membranes of virulence factors secreted by bacterial pathogens. Bacterial hyaluronidase (HYAL), which is produced by a number of invasive Gram-positive bacteria, is selected as a model compound to prove the concept. Our electrochemical setup takes advantage of the flat surface of indium tin oxide/poly(ethylene terephthalate) (ITO/PET) electrodes for their assembly with the nanoporous membrane. The proposed analytical method, based on the electrical monitoring of the steric/electrostatic nanochannels blocked upon formation of an antibody-HYAL immunocomplex, reached detection limits as low as 64 UI/mL (17.3 U/mg) HYAL. The inert surface of the ITO/PET electrodes together with the anti-biofilm properties of the 20 nm pore-sized alumina membranes allows for culturing the bacteria, capturing the secreted enzymes inside the nanochannels, and removing the cells before the electrochemical measurement. Secreted HYAL at levels of 1000 UI/mL (270 U/mg) are estimated in Gram-positive Staphylococcus aureus cultures, whereas low levels are detected for Gram-negative Pseudomonas aeruginosa (used as a negative control). Finally, HYAL secretion inhibition by RNAIII-inhibiting peptide (YSPWTNF-NH2) is also monitored, opening the way for further applications of the developed monitoring system for evaluation of the antivirulence potential of different compounds. This label-free method is rapid and cheap, avoiding the use of the time-consuming sandwich assays. We envisage future applications for monitoring of bacterial virulence/invasion as well as for testing of novel antimicrobial/antivirulence agents.

Multifunctional ZnO NPs-chitosan-gallic acid hybrid nanocoating to overcome contact lenses associated conditions and discomfort.

Contact lenses (CL) provide visual correction but their use may also induce several adverse effects causative of discomfort and conditions that lead to stop or discontinue their use. Discomfort is mainly caused by insufficient wetting, impairment of the antioxidant defence system and eye infections. The current work reports on a single step sonochemical coating of CL with ZnO nanoparticles (NPs), chitosan (CS) and gallic acid (GA). GA and CS are expected to improve the comfort of CL by imparting respectively antioxidant properties and enhanced wettability, while their combination with ZnO NPs provides the CL with antimicrobial properties. The ternary composite coating presents high antibacterial efficiency (>4.5 logs reduction) against S. aureus causative of CL-related conditions, and maintains good biocompatibility (>72%) with human cell lines. The obtained multi-functionality on the CL did not affect their geometry and refractive properties.