Rational design and testing of new urease inhibitors to prevent urinary catheter blockage.

Catheter associated urinary tract infections (CAUTI) caused by urease-positive organisms can lead to catheter blockage: urease metabolizes urea in urine to ammonia causing an increase in pH and hence precipitation of struvite and apatite salts into the catheter lumen and bladder leading to blockage. Acetohydroxamic acid (AHA) is the only urease inhibitor currently approved for patient use, however, it is rarely used owing to its side effects. Here, we report the identification and development of new urease inhibitors discovered using a rational drug design approach.

A new catheter-integrated drug-delivery system for controlled intravesical mitomycin C release.

Background: Intravesical treatment of bladder cancer is preferred over systemic administration. However, the efficacy of intravesical instillations is challenged by the periodic voiding that flushes out the instilled drug and ultimately reduces drug exposure to the bladder epithelium. Here, we demonstrate a new catheter-integrated drug-delivery concept that utilizes a silicone-based interpenetrating polymer network (IPN) as material for the catheter balloon, to facilitate continuous release of the bladder cancer adjuvant, Mitomycin C, from a balloon-reservoir to the urinary bladder.

Enhanced Antibiotic Tolerance of an Multispecies Uropathogen Biofilm Model, Useful for Studies of Catheter-Associated Urinary Tract Infections.

Catheter-associated urinary tract infections (CAUTI) are a common clinical concern as they can lead to severe, persistent infections or bacteremia in long-term catheterized patients. This type of CAUTI is difficult to eradicate, as they are caused by multispecies biofilms that may have reduced susceptibility to antibiotics. Many new strategies to tackle CAUTI have been proposed in the past decade, including antibiotic combination treatments, surface modification and probiotic usage.

Molecular-Gated Drug Delivery Systems Using Light-Triggered Hydrophobic-to-Hydrophilic Switches.

A photoresponsive molecular-gated drug delivery system (DDS) based on silicone-hydrogel (poly(HEMA--PEGMEA)) interpenetrating polymer networks (IPNs) functionalized with carboxylated spiropyran (SPCOOH) was designed and demonstrated as an on-demand DDS. The triggered-release mechanism relies on controlling the wetting behavior of the surface by light, exploiting different hydrophobicities between the "closed" and "open" isomers of spiropyran as a photoswitchable molecular gate on the surface of IPN (SP-photogated IPN). Light-triggered release of doxycycline (DOX) as a model drug indicated that the spiropyran (SP) molecules provide a hydrophobic layer around the drug carrier and have a good gate-closing efficiency for IPNs with 20-30% hydrogel content.

A Novel Device-Integrated Drug Delivery System for Local Inhibition of Urinary Tract Infection.

Catheter-associated urinary tract infection (CAUTI) is a frequent community-acquired infection and the most common nosocomial infection. Here, we developed a novel antimicrobial catheter concept that utilizes a silicone-based interpenetrating polymer network (IPN) as balloon material to facilitate a topical slow-release prophylaxis of antibacterial agents across the balloon to the urinary bladder. The balloon material was achieved by modifying low shore hardness silicone tubes with a hydrogel interpenetrating polymer in supercritical CO using the sequential method.

Evaluating Efficacy of Antimicrobial and Antifouling Materials for Urinary Tract Medical Devices: Challenges and Recommendations.

In Europe, the mean incidence of urinary tract infections in intensive care units is 1.1 per 1000 patient-days. Of these cases, catheter-associated urinary tract infections (CAUTI) account for 98%.

Controlled Release of Plectasin NZ2114 from a Hybrid Silicone-Hydrogel Material for Inhibition of Staphylococcus aureus Biofilm.

is a major human pathogen in catheter-related infections. Modifying catheter material with interpenetrating polymer networks is a novel material technology that allows for impregnation with drugs and subsequent controlled release. Here, we evaluated the potential for combining this system with plectasin derivate NZ2114 in an attempt to design an biofilm-resistant catheter.

Enhanced plasmid loss in bacterial populations exposed to the antimicrobial compound irgasan delivered from interpenetrating polymer network silicone hydrogels.

The spread of antimicrobial resistance, usually mediated by horizontal transfer of plasmids, limits the options of treating bacterial infections and thereby poses a crucial human health problem. The disturbance of plasmid stability within bacterial species in clinical environments serves as a novel strategy to reduce the development and dissemination of antibiotic resistance. We tested the ability of irgasan to destabilize plasmids from Escherichia coli K-12 cells when added directly into liquid growth medium at concentrations below levels of marked bacterial growth inhibition, or when released into liquid growth medium from irgasan-impregnated Interpenetrating Polymer Network (IPN) silicone hydrogel objects, a novel technology developed as drug-delivery platform.

Co-release of dicloxacillin and thioridazine from catheter material containing an interpenetrating polymer network for inhibiting device-associated Staphylococcus aureus infection.

Approximately half of all nosocomial bloodstream infections are caused by bacterial colonization of vascular catheters. Attempts have been made to improve devices using anti-adhesive or antimicrobial coatings; however, it is often difficult to bind coatings stably to catheter materials, and the low amounts of drug in thin-film coatings limit effective long-term release. Interpenetrating polymer networks (IPNs) are polymer hybrid materials with unique drug release properties.

Investigation of pharmaceuticals in processed animal by-products by liquid chromatography coupled to high-resolution mass spectrometry.

There is an on-going trend for developing more sustainable salmon feed in which traditionally applied marine feed ingredients are replaced with alternatives. Processed animal products (PAPs) have been re-authorized as novel high quality protein ingredients in 2013. These PAPs may harbor undesirable substances such as pharmaceuticals and metabolites which are not previously associated with salmon farming, but might cause a potential risk for feed and food safety.

3D Printed Silicone-Hydrogel Scaffold with Enhanced Physicochemical Properties.

Scaffolds with multiple functionalities have attracted widespread attention in the field of tissue engineering due to their ability to control cell behavior through various cues, including mechanical, chemical, and electrical. Fabrication of such scaffolds from clinically approved materials is currently a huge challenge. The goal of this work was to fabricate a tissue engineering scaffold from clinically approved materials with the capability of delivering biomolecules and direct cell fate.

Sustained prevention of biofilm formation on a novel silicone matrix suitable for medical devices.

Bacterial colonization and biofilm formation on medical devices constitute major challenges in clinical long-term use of e.g. catheters due to the risk of (re)infection of patients, which would result in additional use of antibiotics risking bacterial resistance development.

Soft hydrogels interpenetrating silicone--A polymer network for drug-releasing medical devices.

Materials for the next generation of medical devices will require not only the mechanical stability of current devices, but must also possess other properties such as sustained release of drugs in a controlled manner over a prolonged period of time. This work focuses on creating such a sophisticated material by forming an interpenetrating polymer network (IPN) material through modification of silicone elastomers with a poly(2-hydroxyethyl methacrylate) (PHEMA)-based hydrogel. IPN materials with a PHEMA content in the range of 13%-38% (w/w) were synthesized by using carbon dioxide-based solvent mixtures under high pressure.

Safety evaluation for a biodiesel process using prion-contaminated animal fat as a source.

Background: Due to the bovine spongiform encephalopathy (BSE), specified risk material (SRM) as well as animal meat and bone meal (MBM) are banned from the food and feed chain because of a possible infection with pathogenic prions (PrP(Sc)). Nowadays, prions are widely accepted to be responsible for TSE(transmissible spongiform encephalopathies)-caused illnesses like BSE and scrapie, and especially for the occurrence of the new variant of CJD in humans. Presently, SRM and MBM are burnt under high temperatures to avoid any hazards for humans, animals or the environment.