Quercetin-Crosslinked Chitosan Films for Controlled Release of Antimicrobial Drugs

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.

Prolonged Antibacterial Activity in Tannic Acid–Iron Complexed Chitosan Films for Medical Device Applications

“…This was also observed by Siripatrawan and Harte [ 23 ], who highlighted that due to high intramolecular interactions between polyphenol and CS, the hydrophilicity of the film decreased. Moreover, the contact angle values obtained here are close to those observed in a previous work with CS and quercetin, a polyphenolic molecule, whose values were about 104 ± 5° [ 13 ].…”

“…The FTIR analyses ( Figure 2 ) show the expected bands of TA, which are the hydroxyl groups (O-H) H-bonded around 3600–3000 cm −1 , the characteristic bands of aromatic esters with carbonyl groups C=O stretching at 1716 cm −1 and C–O stretching at 1199 cm −1 , and C=C aromatic ring stretching between 1600 and 1500 cm −1 . For films crosslinked with TA, without and with Fe, the main peaks corresponding to the CS sugar unit are unchanged, meaning that the sugar structure of CS itself is not affected, as already observed in a previous work with quercetin, a polyphenol used as crosslinker [ 13 ]. By comparing the films with and without TA (CS-TA and CS), some differences are observed in the amide bands at 1644 and 1540 cm −1 ; the amide I band appears enlarged and the amide II band is slightly shifted, suggesting an interaction between CS nitrogen atoms and TA.…”

“…Different approaches have been developed to overcome this problem, which are mainly based on the use of molecules inducing ionic interactions and crosslinkers [ 9 , 10 ]. However, despite the promising results, short-lasting releases and antimicrobial effects (usually within the first week) were obtained [ 11 , 12 , 13 ]. Thus, there is still the need for a solution able to efficiently address infection prevention for longer periods than what is normally reported (i.e., one week).…”

A Bioengineered Quercetin-Loaded 3D Bio-Polymeric Graft for Tissue Regeneration and Repair

“…The interconnected polymeric 3D ultrastructure between alginate, gelatin, and calcium chloride was established due to cross-linkage for the entrapment of the quercetin drug molecule in the matrix. It was reported that quercetin also has a cross-linking property and is widely used for the cross-linking of polymers to enhance the stability of the polymer [ 45 , 46 , 47 ].…”

Validation of Spectrophotometric Method to Quantify Quercetin in the in Vitro Dissolution Study of Self Nano-Emulsifying Drug Delivery System (Snedds)

“…It is contained in abundance in consumable plants in Indonesia, such as onions, apples, various types of berries, nuts, seeds, and various types of leaves and vegetables. Quercetin has been reported to have anticarcinogenic, anti-inflammatory, antiulcer, hypoallergenic, antiviral, and antidiabetic activities (Mukhopadhyay & Prajapati, 2015;Nguyen & Bhattacharya, 2022;Vipin et al, 2020;Wiggers et al, 2022).…”