Probing the interaction of ex situ biofilms with plasmonic metal nanoparticles using surface-enhanced Raman spectroscopy.

Biofilms are complex environments where matrix effects from components such as extracellular polymeric substances and proteins can strongly affect SERS performance. Here the interactions between SERS-enhancing Ag and Au particles were studied using ex situ biofilms (es-biofilms), which were more homogenous than in situ biofilm samples. This allowed systematic quantitative studies, where samples could be accurately diluted and analysed, to be carried out. Strong signals from intrinsic marker compounds were found for the Pseudomonas aeruginosa and Staphylococcus aureus extracted es-biofilms, which the standard addition method showed were due to 2 × 10-3 mol dm-3 pyocyanin or the equivalent of 1 × 10-4 mol dm-3 adenine, respectively. The es-biofilms hindered aggregation of Ag colloids more than Au but for both Au and Ag nanospheres the presence of es-biofilm reduced SERS signals through a combination of poorer aggregation and blocking of surface sites. For Ag, the effect of lower aggregation was to reduce the signals by a factor of ca. 2×, while site blocking gave a further 10× reduction for adenine. Similar results were found for Au nanospheres with adenine, although these particles gave low enhancement with pyocyanin. Nanostars were found to be unaffected by reduced aggregation and also showed lower site blocking effects, giving more reproducible signals than those from aggregated particles, which compensated for their lower enhancement factor. These results provide a rational basis for selecting enhancing substrates for use in in situ studies, where the further complexity means that it is important to begin with well-understood and controllable enhancing media.

Time-Resolved Dynamics of Struvite Crystallization: Insights from the Macroscopic to Molecular Scale.

The crystallization of magnesium ammonium phosphate hexahydrate (struvite) often occurs under conditions of fluid flow, yet the dynamics of struvite growth under these relevant environments has not been previously reported. In this study, we use a microfluidic device to evaluate the anisotropic growth of struvite crystals at variable flow rates and solution supersaturation. We show that bulk crystallization under quiescent conditions yields irreproducible data owing to the propensity of struvite to adopt defects in its crystal lattice, as well as fluctuations in pH that markedly impact crystal growth rates. Studies in microfluidic channels allow for time-resolved analysis of seeded growth along all three principle crystallographic directions and under highly controlled environments. After having first identified flow rates that differentiate diffusion and reaction limited growth regimes, we operated solely in the latter regime to extract the kinetic rates of struvite growth along the [100], [010], and [001] directions. In situ atomic force microscopy was used to obtain molecular level details of surface growth mechanisms. Our findings reveal a classical pathway of crystallization by monomer addition with the expected transition from growth by screw dislocations at low supersaturation to that of two-dimensional layer generation and spreading at high supersaturation. Collectively, these studies present a platform for assessing struvite crystallization under flow conditions and demonstrate how this approach is superior to measurements under quiescent conditions.

Luminescent Lanthanide Cyclen-Based Enzymatic Assay Capable of Diagnosing the Onset of Catheter-Associated Urinary Tract Infections Both in Solution and within Polymeric Hydrogels.

Herein we present a supramolecular (delayed luminescent) Eu(III)-based pH-responsive probe/sensor with the ability to detect the urease-mediated hydrolysis of urea in aqueous solution. A series of photophysical titrations show this Eu(III) chelate behaves as an "on-off" luminescent switching probe, with its luminescence being quenched upon urea being enzymatically converted into ammonia and carbon dioxide. Calculation of the rate constant (k) and activation energy (Ea) for this hydrolysis reaction are detailed; the results demonstrate a direct observation of enzymatic activity in solution by the sensor. The potential application of this probe in detecting the onset of catheter-associated urinary tract infections (CAUTIs) is also demonstrated by incorporating 1.Eu into water-permeable hydrogels that can be utilized as an alternative coating for catheters.

Rapid One-Pot Preparation of Large Freestanding Nanoparticle-Polymer Films.

2D arrays of metal nanoparticles formed at liquid-liquid interfaces have been fixed in situ to a thin polymer support to create freestanding large (cm2 ) composite films where the particles remain exposed rather than being trapped within the polymer. Applications of these flexible robust 2D nanoparticle arrays as sensors, thin film conductors, antimicrobial coatings, and dip-in catalysts are shown.

Photochemically Controlled Drug Dosing from a Polymeric Scaffold.

PURPOSE: To develop the first photoactive biomaterial coating capable of controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin (DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. METHODS: Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and characterised via NMR spectroscopy and mass spectrometry following chromatographic purification. Conjugate photolysis was investigated in acetonitrile solution and within the pMEA matrix following exposure to low-power 365 nm irradiation. Photo-liberation of drug from pMEA into phosphate buffered saline was monitored using UV-vis spectroscopy. RESULTS: The synthetic procedures yielded the desired drug conjugates with full supporting characterisation. Drug regeneration through photolysis of the synthesised conjugates was successful in both acetonitrile solution and within the pMEA scaffold upon UV irradiation. Conjugates were retained within the pMEA scaffold with exclusive drug liberation following irradiation and increased drug dose with increasing exposure. Multi-dosing capacity was demonstrated though the ability of successive irradiation periods to generate further bursts of drug. CONCLUSION: This study demonstrates the first application of photochemically controlled drug release from a biomaterial coating and the feasibility of using pMEA as a scaffold for housing the photoactive drug-DMB conjugates.

An Infection-Responsive Approach To Reduce Bacterial Adhesion in Urinary Biomaterials.

Infection is an inevitable consequence of chronic urinary catheterization with associated problems of recurrent catheter encrustation and blockage experienced by approximately 50% of all long-term catheterized patients. In this work, we have exploited, for the first time, the reported pathogen-induced elevation of urine pH as a trigger for "intelligent" antimicrobial release from novel hydrogel drug delivery systems of 2-hydroxyethyl methacrylate and vinyl-functionalized nalidixic acid derivatives, developed as candidate infection-resistant urinary catheter coatings. Demonstrating up to 20-fold faster rates of drug release at pH 10, representing infected urine pH, than at pH 7 and achieving reductions of up to 96.5% in in vitro bacterial adherence, our paradigm of pH-responsive drug delivery, which requires no external manipulation, therefore represents a promising development toward the prevention of catheter-associated urinary tract infections in vivo.

Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterization.

Engineered cocrystals offer an alternative solid drug form with tailored physicochemical properties. Interestingly, although cocrystals provide many new possibilities, they also present new challenges, particularly in regard to their design and large-scale manufacture. Current literature has primarily focused on the preparation and characterization of novel cocrystals typically containing only the drug and coformer, leaving the subsequent formulation less explored. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder. In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Using ibuprofen and isonicotinamide as a model cocrystal reagent pair, formulations extruded with a small molecular matrix carrier (xylitol) were examined to be intimate mixtures wherein the newly formed cocrystal particulates were physically suspended in a matrix. With respect to formulations extruded using polymeric carriers (Soluplus and Eudragit EPO, respectively), however, there was no evidence within PXRD patterns of either crystalline ibuprofen or the cocrystal. Importantly, it was established in this study that an appropriate carrier for a cocrystal reagent pair during HME processing should satisfy certain criteria including limited interaction with parent reagents and cocrystal product, processing temperature sufficiently lower than the onset of cocrystal Tm, low melt viscosity, and rapid solidification upon cooling.

Hydrogel-Forming Microneedle Arrays Made from Light-Responsive Materials for On-Demand Transdermal Drug Delivery.

We describe, for the first time, stimulus-responsive hydrogel-forming microneedle (MN) arrays that enable delivery of a clinically relevant model drug (ibuprofen) upon application of light. MN arrays were prepared using a polymer prepared from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) by micromolding. The obtained MN arrays showed good mechanical properties. The system was loaded with up to 5% (w/w) ibuprofen included in a light-responsive 3,5-dimethoxybenzoin conjugate. Raman spectroscopy confirmed the presence of the conjugate inside the polymeric MN matrix. In vitro, this system was able to deliver up to three doses of 50 mg of ibuprofen upon application of an optical trigger over a prolonged period of time (up to 160 h). This makes the system appealing as a controlled release device for prolonged periods of time. We believe that this technology has potential for use in "on-demand" delivery of a wide range of drugs in a variety of applications relevant to enhanced patient care.

Hydrogel Antimicrobial Capture Coatings for Endotracheal Tubes: A Pharmaceutical Strategy Designed to Prevent Ventilator-Associated Pneumonia.

This paper presents a novel strategy for the prevention of ventilator-associated pneumonia that involves coating poly(vinyl chloride, PVC) endotracheal tubes (ET) with hydrogels that may be subsequently used to entrap nebulized antimicrobial solutions. Candidate hydrogels were prepared containing a range of ratios of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) from 100:0 to 70:30 using free radical polymerization and, when required, simultaneous attachment to PVC was performed. The mechanical properties, glass transition temperatures, swelling kinetics, uptake of gentamicin from an aqueous medium, and gentamicin release were characterized. Increasing the MAA content of the hydrogels significantly decreased the ultimate tensile strength, % elongation at break, Young's modulus, and increased the glass transition temperature, the swelling ratio, and gentamicin uptake. Microbial (Staphylococcus aureus and Pseudomonas aeruginosa) adherence to control (drug-free) hydrogels was observed; however, while adherence to gentamicin-containing p(HEMA) occurred, no adherence occurred to gentamicin-containing HEMA:MAA copolymers. Antimicrobial persistence of gentamicin-containing hydrogels was examined by determining the zone of inhibition against each microorganism on successive days. Hydrogel composition affected the observed antimicrobial persistence, with the hydrogel composed of 70:30 HEMA:MAA exhibiting >20 days persistence against S. aureus and P. aeruginosa, respectively. To simulate clinical use, the hydrogels (coated onto PVC) were first exposed to a nebulized solution of gentamicin (4 mL, 80 mg for 20 min), and then to nebulized bacteria (4 mL ca. 1×10(9) colony forming units mL(-1), 30 min). Viable bacteria were not observed on the gentamicin-treated p(HEMA: MAA) copolymers, whereas growth was observed on gentamicin-treated p(HEMA). In light of the excellent antimicrobial activity and physicochemical properties, p(HEMA: MAA) copolymers composed of ratios of 80:20 or 70:30 HEMA: MAA were identified as potentially useful coatings of endotracheal tubes to be used in conjunction with the clinical nebulization of gentamicin and designed for the prevention of ventilator-associated pneumonia.

Preaggregated Ag nanoparticles in dry swellable gel films for off-the-shelf surface-enhanced Raman spectroscopy.

Large, thin (50 µm) dry polymer sheets containing numerous surface-enhanced Raman spectroscopy (SERS) active Ag nanoparticle aggregates have been prepared by drying aqueous mixtures of hydroxyethylcelloulose (HEC) and preaggregated Ag colloid in 10 × 10 cm molds. In these dry films, the particle aggregates are protected from the environment during storage and are easy to handle; for example, they can be cut to size with scissors. When in use, the highly swellable HEC polymer allowed the films to rapidly absorb aqueous analyte solutions while simultaneously releasing the Ag nanoparticle aggregates to interact with the analyte and generate large SERS signals. Either the films could be immersed in the analyte solution or 5 µL droplets were applied to the surface; in the latter method, the local swelling caused the active area to dome upward, but the swollen film remained physically robust and could be handled as required. Importantly, encapsulation and release did not significantly compromise the SERS performance of the colloid; the signals given by the swollen films were similar to the very high signals obtained from the parent citrate-reduced colloid and were an order of magnitude larger than a commercially available nanoparticle substrate. These "Poly-SERS" films retained 70% of their SERS activity after being stored for 1 year in air. The films were sufficiently homogeneous to give a standard deviation of 3.2% in the absolute signal levels obtained from a test analyte, primarily due to the films' ability to suppress "coffee ring" drying marks, which meant that quantitative analysis without an internal standard was possible. The majority of the work used aqueous thiophenol as the test analyte; however, preliminary studies showed that the Poly-SERS films could also be used with nonaqueous solvents and for a range of other analytes including theophylline, a therapeutic drug, at a concentration as low as 1.0 × 10(-5) mol dm(-3) (1.8 mg/dm(3)), well below the sensitivity required for theophylline monitoring where the target range is 10-20 mg/dm(3).

Comparison of Superhydrophilic, Liquid-Like, Liquid-Infused, and Superhydrophobic Surfaces in Preventing Catheter-Associated Urinary Tract Infection and Encrustation.

Over the past decade, superhydrophilic zwitterionic surfaces, slippery liquid-infused porous surfaces, covalently attached liquid-like surfaces, and superhydrophobic surfaces have emerged as the most promising strategies to prevent biofouling on biomedical devices. Despite working through different mechanisms, they have demonstrated superior efficacy in preventing the adhesion of biomolecules (e.g., proteins and bacteria) compared with conventional material surfaces. However, their potential in combating catheter-associated urinary tract infection (CAUTI) remains uncertain. In this research, we present the fabrication of these four coatings for urinary catheters and conduct a comparative assessment of their antifouling properties through a stepwise approach. Notably, the superhydrophilic zwitterionic coating demonstrated the highest antifouling activity, reducing 72.3% of fibrinogen deposition and over 75% of bacterial adhesion (Escherichia coli and Staphylococcus aureus) when compared with an uncoated polyvinyl chloride (PVC) surface. The zwitterionic coating also exhibited robust repellence against blood and improved surface lubricity, decreasing the dynamic coefficient of friction from 0.63 to 0.35 as compared with the PVC surface. Despite the fact that the superhydrophilic zwitterionic and hydrophobic liquid-like surfaces showed great promise in retarding crystalline biofilm formation in the presence of Proteus mirabilis, it is worth noting that their long-term antifouling efficacy may be compromised by the proliferation and migration of colonized bacteria as they are unable to kill them or inhibit their swarming. These findings underscore both the potential and limitations of these ultralow fouling materials as urinary catheter coatings for preventing CAUTI.

Use of solid thermolytic salts to facilitate microwave-induced in situ amorphization.

Moisture was frequently used as dielectric heating source in classical microwave-able systems to facilitate microwave-induced in situ amorphization, however such systems may face the potential of drug hydrolysis. In this study, solid thermolytic salts were proposed to function as moisture substitutes and their feasibility and impacts on microwave-induced in situ amorphization were investigated. It was found that NH4HCO3 was a promising solid alkaline salt to facilitate both microwave-induced in situ amorphization and in situ salt formation of acidic indomethacin (IND). Moreover, it could improve the chemical stability of the drug and the dissolution performance of compacts relative to classical moisture-based compacts upon microwaving. Further mechanistic study suggested that the in situ amorphization occurred prior to the in situ salt formation, especially in formulations with low drug loadings and high solid salt mass ratios. For compacts with low polymer ratios, in situ salt formation took place subsequently, where the previously amorphized IND within compacts could interact with the NH3 gas produced in situ by the decomposition of NH4HCO3 and form the ammonium IND salt. Microwaving time showed great impacts on the decomposition of NH4HCO3 and the in situ generation of water and NH3, which indirectly affected the amorphization and salt formation of IND. In comparison to the moisture-based systems, the NH4HCO3-based system showed a number of advantages, including the reduced potential of IND hydrolysis due to the absence of absorbed moisture, a wider category of applicable polymeric carriers other than hygroscopic polymers, and an increase in drug loading up to 50% (w/w).

Comparing an Integrated Amphiphilic Surfactant to Traditional Hydrophilic Coatings for the Reduction of Catheter-Associated Urethral Microtrauma.

Hydrophilic-coated intermittent catheters have improved the experience of intermittent urinary catheterization for patients compared to conventional gel-lubricated uncoated catheters. However, the incorporation of polyvinylpyrrolidone (PVP) within hydrophilic coatings can lead to significant issues with coating dry-out. Consequently, increased force on catheter withdrawal may cause complications, including urethral microtrauma and pain. Standard methods of evaluating catheter lubricity lack physiological relevance and an understanding of the surface interaction with the urethra. The tribological performance and urethral interaction of commercially available hydrophilic PVP-coated catheters and a coating-free integrated amphiphilic surfactant (IAS) catheter were evaluated by using a biomimetic urethral model designed from a modified coefficient of friction (CoF) assay. T24 human urothelial cells were cultured on customized silicone sheets as an alternate countersurface for CoF testing. Hydrophilic PVP-coated and coating-free IAS catheters were hydrated and the CoF obtained immediately following hydration, or after 2 min, mimicking in vivo indwell time for urine drainage. The model was observed for urethral epithelial cell damage postcatheterization. The majority of hydrophilic PVP-coated catheters caused significantly greater removal of cells from the monolayer after 2 min indwell time, compared to the IAS catheter. Hydrophilic PVP-coated catheters were shown to cause more cell damage than the coating-free IAS catheter. A biomimetic urethral model provides a more physiologically relevant model for understanding the factors that govern the frictional interface between a catheter surface and urethral tissue. From these findings, the use of coating-free IAS catheters instead of hydrophilic PVP-coated catheters may help reduce urethral microtrauma experienced during catheter withdrawal from the bladder, which may lead to a lower risk of infection.

Dual stimuli-responsive delivery system for self-regulated colon-targeted delivery of poorly water-soluble drugs.

Inflammatory bowel disease (IBD) are chronic inflammatory conditions which cause significant patient morbidity. Local drug delivery to the colon can improve treatment efficacy and reduce side effects associated with IBD treatment. Smart drug delivery systems are designed to regulate the release of therapeutic agents at the desired site of action. pH-responsive drug carriers have been previously utilised for improved oral drug delivery beyond stomach harsh conditions. Additionally, the colon possesses a diverse microbiome secreting bioactive molecules e.g., enzymes, that can be exploited for targeted drug delivery. We herein synthesised and characterised a 2-hydroxyethyl methacrylate and methacrylic acid copolymer, crosslinked with an azobenzyl crosslinker, that displayed pH- and enzyme-responsive properties. The swelling and drug release from hydrogel were analysed in pH 1.2, 6.5 and 7.4 buffers, and in the presence of rat caecal matter using metronidazole and mesalamine as model BCS Class I and IV drugs, respectively. Swelling studies displayed pH-responsive swelling behaviour, where swelling was maximum at pH 7.4 and minimum at pH 1.2 (69 % versus 32 %). Consequently, drug release was limited in gastric and small intestinal conditions but increased significantly when exposed to colonic conditions containing caecal matter. This system displays promising capacity for achieving colon-targeted drug delivery with enhanced dissolution of poorly water-soluble drugs for local treatment of IBD and other colon-targeted therapies.

Infection-responsive drug delivery from urinary biomaterials controlled by a novel kinetic and thermodynamic approach.

PURPOSE: The pH-dependent physicochemical properties of the antimicrobial quinolone, nalidixic acid, were exploited to achieve 'intelligent' drug release from a potential urinary catheter coating, poly(2-hydroxyethylmethacrylate) (p(HEMA)), in direct response to the elevated pH which occurs at the onset of catheter infection. METHODS: p(HEMA) hydrogels, and reduced-hydrophilicity copolymers incorporating methyl methacrylate, were loaded with nalidixic acid by a novel, surface particulate localization method, and characterized in terms of pH-dependent drug release and microbiological activity against the common urease-producing urinary pathogen Proteus mirabilis. RESULTS: The pH-dependent release kinetics of surface-localized nalidixic acid were 50- and 10-fold faster at pH 9, representing the alkaline conditions induced by urease-producing urinary pathogens, compared to release at pH 5 and pH 7 respectively. Furthermore, microbiological activity against P. mirabilis was significantly enhanced after loading surface particulate nalidixic acid in comparison to p(HEMA) hydrogels conventionally loaded with dispersed drug. The more hydrophobic methyl methacrylate-containing copolymers also demonstrated this pH-responsive behavior, but additionally exhibited a sustained period of zero-order release. CONCLUSIONS: The paradigm presented here provides a system with latent, immediate infection-responsive drug release followed by prolonged zero-order antimicrobial delivery, and represents an 'intelligent', infection-responsive, self-sterilizing biomaterial.

Photosensitiser-incorporated microparticles for photodynamic inactivation of bacteria.

Antimicrobial resistance is an ever-growing global concern, making the development of alternative antimicrobial agents and techniques an urgent priority to protect public health. Antimicrobial photodynamic therapy (aPDT) is one such promising alternative, which harnesses the cytotoxic action of reactive oxygen species (ROS) generated upon irradiation of photosensitisers (PSs) with visible light to destroy microorganisms. In this study we report a convenient and facile method to produce highly photoactive antimicrobial microparticles, exhibiting minimal PS leaching, and examine the effect of particle size on antimicrobial activity. A ball milling technique produced a range of sizes of anionic p(HEMA-co-MAA) microparticles, providing large surface areas available for electrostatic attachment of the cationic PS, Toluidine Blue O (TBO). The TBO-incorporated microparticles showed a size-dependent effect on antimicrobial activity, with a decrease in microparticle size resulting in an increase in the bacterial reductions achieved when irradiated with red light. The >6 log10Pseudomonas aeruginosa and Staphylococcus aureus reductions (>99.9999%) achieved within 30 and 60 min, respectively, by TBO-incorporated >90 µm microparticles were attributed to the cytotoxic action of the ROS generated by TBO molecules bound to the microparticles, with no PS leaching from these particles detected over this timeframe. TBO-incorporated microparticles capable of significantly reducing the bioburden of solutions with short durations of low intensity red light irradiation and minimal leaching present an attractive platform for various antimicrobial applications.

The effects of surfactants on the performance of polymer-based microwave-induced in situ amorphization.

Microwave-induced in situ amorphization is a novel technology for preparing amorphous solid dispersions (ASDs) to address the challenges of their long-term physical stability and downstream processing. To date, only few types of dielectric materials have been reported for microwave-induced in situ amorphization, which restricted the extensive research of this technology. This study aimed to investigate the feasibility and mechanisms of utilizing the non-ionic surfactants, i.e. Kollisolv P124, Kolliphor RH40, D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), Tween (T) 60 (T60), T65, T80 and T85, as plasticizers to facilitate microwave-induced in situ amorphization. It was found that the successful application of surfactants could be related with their low Tm, low Mw and high HLB. Kolliphor RH40 was selected as a typical surfactant due to its excellent dielectric heating ability, plasticizing effect and solubilizing effect when facilitating amorphization. Then, the dissolution-mediated in situ amorphization mechanism was investigated and intuitively demonstrated. For the most promising formulation, i.e. microwaved systems with Korlliphor RH40 at 1.5 (w/w) plasticizer/polymer ratio, a complete and fast in vitro dissolution was observed relative to the untreated systems. In conclusion, non-ionic surfactants had the potential to facilitate microwave-induced in situ amorphization, which provided a new direction in the formulation designation for microwave-able systems.

Understanding the properties of intermittent catheters to inform future development.

Despite the extensive use of intermittent catheters (ICs) in healthcare, various issues persist for long-term IC users, such as pain, discomfort, infection, and tissue damage, including strictures, scarring and micro-abrasions. A lubricous IC surface is considered necessary to reduce patient pain and trauma, and therefore is a primary focus of IC development to improve patient comfort. While an important consideration, other factors should be routinely investigated to inform future IC development. An array of in vitro tests should be employed to assess IC's lubricity, biocompatibility and the risk of urinary tract infection development associated with their use. Herein, we highlight the importance of current in vitro characterisation techniques, the demand for optimisation and an unmet need to develop a universal 'toolkit' to assess IC properties.

Tetrasodium EDTA for the prevention of urinary catheter infections and blockages.

Long-term catheterised individuals are at significant risk of developing catheter-associated urinary tract infections (CAUTIs), with up to 50% of patients experiencing recurrent episodes of catheter encrustation and blockage. Catheter blockage is a result of accumulation of carbonate apatite and struvite formed upon precipitation of ions within urine due to an infection-induced rise in pH. The aim of this study was to investigate the antimicrobial and anti-encrustation activities of tetrasodium ethylenediaminetetraacetic acid (tEDTA) to evaluate its potential efficacy in preventing CAUTIs and catheter blockages. The antimicrobial activity of tEDTA against uropathogens was assessed using time kill assays performed in artificial urine (AU). Crystallisation studies and in vitro bladder model assays were conducted to investigate the effect of tEDTA on struvite crystallisation and catheter blockage. tEDTA displayed bacteriostatic activity against Proteus mirabilis and prevented precipitation of ions in the AU. Crystallisation studies confirmed tEDTA inhibits struvite nucleation and growth via Mg2+ chelation with 7.63 mM tEDTA, equimolar to the concentration of divalent cations in AU, preventing the formation of crystalline deposits and blockage of Foley catheters for ≥168 h. The promising chelating abilities of low tEDTA concentrations could be exploited to inhibit encrustation and blockage of indwelling catheters. The fundamental research presented will inform our future development of an effective tEDTA-eluting catheter coating aimed at preventing catheter encrustation.

Infection-Triggered, Self-Cleaning Surfaces with On-Demand Cleavage of Surface-Localized Surfactant Moieties.

Biofouling of surfaces is a major cause of infection and leads to significant patient morbidity and mortality within healthcare settings. With ever-increasing concerns over antibiotic resistance and associated challenges in eradicating surface-attached biofilm communities, efficacious antifouling materials are urgently required. We herein describe the development of an inherently antiadherent polymer system with the capacity for on-demand cleavage of surface-localized surfactant moieties. The nonionic surfactant, Triton X-100, was linked to hydrogel monomers via hydrolytically labile ester bonds. Synthesized copolymers exhibited pH-dependent switching of surfactant release, with elution triggered under the alkaline conditions characteristic of catheter-associated urinary tract infections and subsequently slowed down as the pH decreased, representing eradication of infection. In addition, the materials demonstrated complete resistance to adherence of Staphylococcus aureus following 24 h incubation in infected artificial urine, with reductions in adherence of Proteus mirabilis of up to 89% also observed. This dual-pronged approach with active, infection-responsive cleavage of surfactant to enhance the antiadherent properties of the surfactant-modified surfaces represents a promising self-cleaning strategy without associated concerns over bacterial resistance.