Surface engineering of biomedical catheters using N-acetyl cysteine functionalized carboxymethyl chitosan nanosystems to combat biofouling and device-associated infections

Functionalized anti-biofouling nanosystems were developed to engineer the surface of silicone catheters for mitigating the incidence of device-associated infections (DAIs). These infections are typically a consequence of microbial biofilms and antimicrobial resistance (AMR) which lead to increased hospitalization costs and mortality rates. Covalent coupling of N-acetyl cysteine (NAC) with O-carboxymethyl chitosan (O-CMC) was optimized to develop NAC-functionalized CMC nanosystems (NAC-CMC-NS). The coupling was confirmed by nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy and 4, 6-trinitrobenzene sulfonic acid (TNBS) assay indicating 80 f 2 % functionalization efficacy. Subsequently, meropenemloaded NAC-CMC NS exhibited an average particle size of 273 f 4.2 nm with 0.4 f 0.03 polydispersity index (PDI), a zeta potential of-9.15 f 0.5 mV and encapsulation efficiency (EE) of 67 f 3.2%. These functionalized NS employing the dual strategy of contact-killing and meropenem-release, exhibited exceptional antimicrobial activity leading to the 76 f 1.5% and 60 f 1 % inhibition of E. coli and P. aeruginosa biofilms, respectively. After the successful grafting of functionalized NS onto silicone catheters, the resulting substrate remarkably reduced the bacterial colonization, offering a promising solution for reducing DAIs like ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTI). Moreover, the excellent hemocompatibility and low cytotoxicity of these nanovesicles highlight their potential applications for clinical use.