Antimicrobial nanocomposite coatings for rapid intervention against catheter-associated urinary tract infections.

Catheter-associated urinary tract infections (CAUTIs) pose a significant challenge in hospital settings. Current solutions available on the market involve incorporating antimicrobials and antiseptics into catheters. However, challenges such as uncontrolled release leading to undesirable toxicity, as well as the prevalence of antimicrobial resistance reduce the effectiveness of these solutions. Additionally, conventional antibiotics fail to effectively eradicate entrenched bacteria and metabolically suppressed bacteria present in the biofilm, necessitating the exploration of alternative strategies. Here, we introduce a novel polymer-nanocomposite coating that imparts rapid antimicrobial and anti-biofilm properties to coated urinary catheters. We have coated silicone-based urinary catheters with an organo-soluble antimicrobial polymer nanocomposite (APN), containing hydrophobic quaternized polyethyleneimine and zinc oxide nanoparticles, in a single step coating process. The coated surfaces exhibited rapid eradication of drug-resistant bacteria within 10-15 min, including E. coli, K. pneumoniae, MRSA, and S. epidermidis, as well as drug-resistant C. albicans fungi. APN coated catheters exhibited potent bactericidal activity against uropathogenic strains of E. coli, even when incubated in human urine. Furthermore, the stability of the coating and retention of antimicrobial activity was validated even after multiple washes. More importantly, this coating deterred biofilm formation on the catheter surface, and displayed rapid inactivation of metabolically repressed stationary phase and persister cells. The ability of the coated surfaces to disrupt bacterial membranes and induce the generation of intracellular reactive oxygen species (ROS) was assessed through different techniques, such as electron microscopy imaging, flow cytometry as well as fluorescence spectroscopy and microscopy. The surface coatings were found to be biocompatible in an in vivo mice model. Our simple one-step coating approach for catheters holds significant potential owing to its ability to tackle multidrug resistant bacteria and fungi, and the challenge of biofilm formation. This work brings us one step closer to enhancing patient care and safety in hospitals.

Multifunctional Suture Coating for Combating Surgical Site Infections and Mitigating Associated Complications.

Despite advancements in preventive measures and hospital protocols, surgical site infections (SSIs) remain a significant concern following surgeries. Sutures, commonly used for wound closure, can serve as a platform for microbial adherence and contamination, leading to extensive debridement and recurrent antibiotic therapy. The emergence of drug resistance and the formation of biofilms on sutures have further complicated the management of SSIs. Drug-eluting sutures incorporating biocides like triclosan have limitations due to uncontrolled release and associated toxicity. Therefore, there is a need for alternative approaches to impart antimicrobial properties to sutures. In this study, we present a one-step covalent cross-linking method to coat surgical sutures with an antimicrobial small molecule, quaternary benzophenone-based antimicrobial (QSM). Additionally, the sutures are dip-coated with ibuprofen, a nonsteroidal anti-inflammatory drug with analgesic properties. The coated sutures maintained their morphological and tensile properties after in vivo implantation. The antimicrobial coating demonstrated efficacy against a broad-spectrum pathogens, including drug-resistant bacteria and fungi. The optimized formulation retained its biodegradability in vivo. Furthermore, the coated sutures exhibited ∼3 log reduction in methicillin-resistant Staphylococcus aureus (MRSA) burden in a subcutaneous implantation mouse model. Overall, this multifunctional coating provides antimicrobial properties to surgical sutures while preserving their mechanical integrity and biodegradability. These coated sutures have the potential to address the challenge of SSIs and contribute to improved surgical outcomes.

Engineering Photo-Crosslinked Antimicrobial Coating to Tackle Catheter-Associated Infections In Vivo.

Microbial colonization on urinary and intravascular catheter surfaces results in steeply rising cases of catheter-associated infections as well as blood stream infections. Currently marketed efforts include impregnation and loading of antimicrobials and antiseptics that leach out into the local environment and inactivate microbes. However, they suffer from uncontrolled release, induction of resistance, and undesired toxicity. Here, in this manuscript, we have developed a photocurable, covalent coating on catheters using quaternary benzophenone-based amide (QSM-1). The coating was found to be active against drug-resistant bacteria and fungi. The coating inactivated stationary and persister cells of superbug MRSA and inhibited the formation of biofilms with retained activity against broad-spectrum bacteria when challenged in realistic urinary conditions. The coating was seen to be biocompatible in vitro and in vivo. Remarkably, the coated catheters showed reduced fouling and >99.9% reduction in bacterial burden when implanted in vivo in a mice model of subcutaneous implantation. We conceive the possibility of application of QSM-1-coated catheters in the healthcare settings to tackle the notorious catheter-associated nosocomial infections.

Polymeric Biomaterials for Prevention and Therapeutic Intervention of Microbial Infections.

The escalating emergence of multidrug-resistant (MDR) pathogens and their ability to colonize into biofilms on a multitude of surfaces have struck global health as a nightmare. The stagnation in the development of antibiotics and the deterioration of clinical pipelines have incited an invigorating search for smart and innovative alternatives in the scientific community. Further, a steep rise in the usage of biomedical devices and implants has resulted in an accelerated occurrence of infections. Toward the goal of mitigation of the aforementioned challenges, antimicrobial polymers have stood out as an astounding option. In this perspective, we highlight our contribution to the field of polymeric biomaterials for tackling antimicrobial resistance (AMR) and infections. Polymers inspired from antimicrobial peptides (AMPs) have been utilized as therapeutic interventions to curb MDR infections and also to rejuvenate obsolete antibiotics. Further, cationic polymers have been used to impart antimicrobial properties to different biomedical surfaces. These cationic polymer-coated surfaces can inactivate pathogens upon contact as well as prevent their biofilm formation. In addition, antimicrobial hydrogels, which are prepared from either inherently antimicrobial polymers or biocide-loaded polymeric hydrogel matrices, have also been engineered. With a brief overview of the progress in the field, detailed elaboration of the polymeric biomaterials for prevention and therapeutic intervention of microbial infections developed by our group is presented. Finally, the challenges in the field of antimicrobial polymers with discussion on the proceedings of polymeric research to alleviate these challenges are discussed.

Advancements in release-active antimicrobial biomaterials: A journey from release to relief.

Escalating medical expenses due to infectious diseases are causing huge socioeconomic pressure on mankind globally. The emergence of antibiotic resistance has further aggravated this problem. Drug-resistant pathogens are also capable of forming thick biofilms on biotic and abiotic surfaces to thrive in a harsh environment. To address these clinical problems, various strategies including antibacterial agent delivering matrices and bactericidal coatings strategies have been developed. In this review, we have discussed various types of polymeric vehicles such as hydrogels, sponges/cryogels, microgels, nanogels, and meshes, which are commonly used to deliver antibiotics, metal nanoparticles, and biocides. Compositions of these polymeric matrices have been elaborately depicted by elucidating their chemical interactions and potential activity have been discussed. On the other hand, various implant/device-surface coating strategies which exploit the release-active mechanism of bacterial killing are discussed in elaboration. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.