Polysaccharides-Catechols Films Loaded with Antibiotic as Antibacterial Drug Release System

Natural polymer-based films, due to their favorable biological and mechanical properties, have demonstrated great potential as coatings for biomedical applications. Among them, polysaccharides, e.g. agarose, dextran and chitosan, have been both widely studied as films, coating materials and as drug controlled release systems [1]. However, in order to control the release kinetic, crosslinkers are usually added to these natural polymers since the crosslinking degree is known to greatly influence the release kinetic. In this light, crosslinkers have been used, ranging from surfactants (e.g. tween, pluronic), chemicals (e.g. glutaraldehyde, citric acid) or natural ones, such as genipin, and phenolic compounds, in particular catechols such as dopamine, tannic acid, and quercetin [2]. These natural crosslinkers are of particular interest because they have been demonstrated to have of their own antibacterial and anti-inflammatory properties. Furthermore, natural catechol moieties can be also used for surface functionalization, once again more ecofriendly than common silanization, phosphonate chemistry approaches. Adding phenolic compounds to natural polymers would be beneficial for the film cohesion, the control of the release and its link to the implant’s surface, ensuring its biological properties and stability at longer term.<br/>In this study, different biopolymers, herein chitosan (CHI) and agarose (AG), and catechols tannic acid (TA) and quercitin (Q) have been investigated. Different formulations and two antibiotics, gentamicin (GS) and trimethoprim (TMP), have been tested. Films were obtained by solvent casting from agarose or chitosan solution (1% w/v) mixed with catechol solutions at different percentage and antibiotic. The resulting films have been evaluated in terms of their release kinetic and their efficiency to be antibacterial at short and medium term (from hours to one month). The antibiotic release has been tested over 1 month in phosphate buffer solution (PBS), and its quantification evaluated by ELISA test or HPLC. The antibacterial effects exerted by the produced films have been assessed against S. aureus and E. Coli by Kirby-Bauer disc diffusion and micro-dilution broth. Physicochemical characterizations of the films have been performed. The surface was composition assessed by XPS-ray photoelectron and FTIR spectroscopies, and the wettability by contact angle.<br/>Results show how quercetin concentrations, ranging from 1 up 30% w/v, when added to chitosan are able to increase the crosslinking degree of the films in a dose-dependent way, influencing the release kinetic of the loaded TMP within the first 6 hours compared to un-crosslinked chitosan. Moreover, high crosslinker concentrations have been found to limit the TMP release, since only 35% of the loaded TMP was released for CHI-30Q. The effectiveness against the tested bacteria was maintained for 6 hours for CHI-30Q-TMP loaded films whereas it reached one day with GS films done in the same condition. When TA was used as crosslinker, the antibacterial effect was sustained up to 7 days with TMP, and for GS an effect was still noticed at day 14 (only 50% of bacterial survival). AG-TA-GS coatings applied on titanium alloy displayed a pronounced controlled release effect for up to 7 days, with GS release concentrations higher than the MIC. Moreover, this coating, grafted through catechol moieties, was stable up to 4 weeks, and efficiently inhibit bacterial activity up to 7 days [3].<br/>Polysaccharides-catechols films loaded with antibiotic appears as a promising approach for antibacterial drug release system. By fine-tuning their composition, they may be a viable and ecofriendly platform to address biomaterial-related infections at medium term.<br/>[1] Barclay et al. – Carbohyd. Polym. 221 (2019) 94<br/>[2] Xu et al. – Prog. Polym. Sci. 87 (2018) 165<br/>[3] Soylu et al. – Frontiers 11 (2021) 678081