Abstract

Natural polymer-based films, due to their favorable biological and mechanical properties, have demonstrated great potential as coatings for biomedical applications. Among them, chitosan films have been widely studied both as coating materials and as controlled drug release systems. Crosslinkers are often used to tune chitosan’s crosslinking degree and thus to control the drug release kinetics. For this purpose, quercetin, a plant-derived natural polyphenol, has gained attention as a crosslinker, mainly for its intrinsic anti-inflammatory, antioxidant, and antibacterial features. In this study, chitosan films crosslinked with three different concentrations of quercetin (10, 20, and 30% w/w) have been used as controlled release systems for the delivery of the antibacterial drug trimethoprim (TMP, 10% w/w). Physicochemical and antimicrobial properties were investigated. Surface wettability and composition of the films were assessed by contact angle measurements, X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR), respectively. The release kinetic of TMP in phosphate-buffered saline (PBS) and 2-(N-morpholino) ethanesulfonic acid (MES) was studied over time. Finally, antibacterial properties were assessed on E. coli and S. aureus through Kirby–Bauer disc diffusion and micro-dilution broth assays. Results show that quercetin, at the tested concentrations, clearly increases the crosslinking degree in a dose-dependent manner, thus influencing the release kinetic of the loaded TMP while maintaining its bactericidal effects. In conclusion, this work demonstrates that quercetin-crosslinked chitosan films represent a promising strategy for the design of antibiotic-releasing coatings for biomedical applications.

Highlights

  • Healthcare-associated infections (HAIs) are defined as all infections occurring in patients while receiving treatment for other conditions

  • Increasing the amount of quercetin leads to higher water contact angle values, which may be explained by the hydrophobic nature of the aromatic rings present in the quercetin structure

  • Quercetin-crosslinked chitosan films have been proposed as short-term antibiotic-release systems

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Summary

Introduction

Healthcare-associated infections (HAIs) are defined as all infections occurring in patients while receiving treatment for other conditions. According to the Center for Diseases Control and Prevention (CDC), HAIs account for an estimated 1.7 million infections and 99,000 associated deaths each year in the United States alone (Healthcare-Associated Infections, 2021). Statistics show that 1 of every 25 patients admitted to a hospital will acquire an HAI, leading to longer hospitalization, readmissions, and, in a worst-case scenario, death. The estimated direct medical cost of HAIs exceeds $30 billion annually in the United States alone (Scott 2009; ODPHP 2021). Chitosan Films for Controlled Release and $3.4 million per year in expenditures reported by the Canadian government (Health Canada 2018). Among the HAIs, biomaterial-associated infections (BAIs) account for more than half of the total infections (Van Epps and Younger 2016). The use of medical devices (such as catheters and implants) is hampered by biofilm-forming microorganisms’ high rate of colonization of their surfaces

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