Engineered chitosan–xanthan gum biopolymers effectively adhere to cells and readily release incorporated antiseptic molecules in a sustained manner

Abstract

The polyelectrolyte complexes that contain anionic xanthan gum and cationic chitosan formed or coalesced into biopolymeric scaffolds. To increase the viscosity and adherent properties of the prepared scaffolds, chitosan–xanthan gum microspheres were prepared by coacervation. The coalesced biopolymer was mixed with CHX to form injectable antibacterial hydrogels. We successfully prepared a biocompatible, antiseptic, chitosan–xanthan gum-based biopolymer with a potential to be used as an effective local antiseptic for acute or chronic periodontitis.

Introduction

Hydrogels are biomaterials used for drug delivery, tissue engineering, and medical devices owing to their high water content and biomimetic properties [1], [2]. Injectable drug-containing hydrogels can be applied to targeted areas for local drug delivery using a syringe, and gelatinized once they are released inside the body [3]. The applied injectable hydrogels can adopt a definite shape and before they are subsequently delivered in a minimally invasive manner, resulting in fast recovery, small scar size, and less pain [4], [5]. The biomedical applications of injectable hydrogels such as in drug delivery have increased owing to their mechanical properties, stability, biocompatibility, and biodegradability [6].

Natural polymers, such as polysaccharides, have diverse structures with different physiological functions and may serve a variety of purposes in biomedical applications owing to their distinctive properties including their pseudoplastic behavior, gelation ability, water binding capacity, and biodegradability [7], [8]. Some polysaccharide-based hydrogels are used to effectively transport pharmaceutical products, and consist of highly hydrophilic polymeric networks into which drugs can be physically incorporated [9].

Xanthan gum, a natural polysaccharide produced by the bacterium Xanthomonas campestris, is used as a thickening agent in food, cosmetic, pharmaceutical, agriculture, textile, and petrochemical industries [10], [11]. It consists of 1,4-linked β-d-glucose residues, and its anionic nature is attributable to the pyruvic acid and glucuronic acid groups in the side chains [10]. Because it is water-soluble and stable at a broad range of temperatures and acidic and alkaline conditions, xanthan gum is used as a gelling agent in aqueous systems for drug delivery [12]. Xanthan gum can retard drug release and exhibit time-independent release kinetics [12]. Xanthan gum-based gel systems are formed by annealing and subsequent cooling [13]. The major rheological properties of xanthan gum include high viscosity at low shear rates, shear-thinning nature, and good resistance to shear degradation [14].

Chitosan is a linear cationic polysaccharide composed of poly-β-(1 → 4)-d-glucosamine and is produced by alkaline deacetylation of chitin [15], [16]. It exhibits excellent biocompatibility, biodegradability, non-toxicity, and adsorption properties [17], [18], [19], [20]. Moreover, chitosan possesses antimicrobial activity [21]. For these reasons, chitosan has been used in several fields such as biomedicine, pharmaceutics, food additives, antimicrobial agents, paper and textiles, and environmental remediation [22], [23], [24], [25], [26], [27]. The polycationic properties of chitosan facilitate the preparation of various polyelectrolyte complexes with natural polyanions such as carboxymethylcellulose [28], alginic acid [29], dextran sulfate [30], carboxymethyl dextran [31], heparin [32], carrageenan [33], and pectin [34]. Chitosan is used as a biomaterial because of these characteristics [35].

Chitosan–xanthan gum biopolymers are formed by ionic interactions between the amino and carboxyl groups of chitosan and xanthan gum, respectively [36]. The biopolymer exhibits pH-sensitive swelling characteristics, which enable the controlled release of entrapped materials (e.g., therapeutic agents, enzymes, and bacteria) [36], [37], [38], [39], [40], [41]. These biopolymers can be converted into various products by modifying the molecular properties of the xanthan gum and chitosan (i.e., molecular weight, degree of acetylation of chitosan, and pyruvic acid content of xanthan gum) and the complexation conditions (i.e., pH of chitosan solution, polymer concentration, complexation time, and mixing ratio [42], [43], [44].

Chlorhexidine (CHX) is a cationic bisbiguanide antiseptic with broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria, yeast, dermatophytes, and some lipophilic viruses [45]. It damages the inner (cytoplasmic) membrane, leading to cell lysis and death [46], [47]. It has low toxicity against mammalian tissue and a strong affinity for skin and mucous membranes [45]. It has been applied in dental treatments for plaque control and gingival inflammation [47].

In this study, we developed a chitosan–xanthan gum biopolymer as a polyelectrolyte complex (PEC) gel, formed by electrostatic attractions in an aqueous solution carrying CHX molecules. The PEC gel was designed to attach the biopolymer to gum tissues effectively and thereby successfully deliver an antiseptic agent.