# Polysaccharide Hydrogels Based on Cellulose and Chitosan for Drug Sustained-Release Applications
## 1 Introduction  
Low-dose cytokine drugs have demonstrated promising therapeutic potential in the treatment of various autoimmune disease [1, 2, 3]. Given the short half-life of cytokines in vivo, frequent injections are necessary to maintain therapeutic concentrations, which can lead to a range of adverse reactions [2, 4]. Therefore, developing injectable drug-loaded sustained-release materials represents an effective strategy to enhance therapeutic efficacy while mitigating side effects. Drug-loaded sustained-release materials can be categorized into organic polymer-based and inorganic non-metallic-based systems. Organic polymers, particularly hydrogels derived from natural sources (e.g., gelatin, cellulose, sodium alginate, hyaluronic acid, and chitosan) and synthetic polymers (e.g., polyacrylic acid [PAA], polyacrylamide [PAM]), dominate this field [5]. However, synthetic organic polymers oftensuffer from issues such as residual toxic cross-linking agents, poor biocompatibility, and lower drug loading capacity compared to their natural counterparts.  
Hydrogels, as three-dimensional porous hydrophilic polymer networks, exhibit superior properties including high water content, flexibility, mechanical strength, biocompatibility, and degradability [6; 7; 8]. Injectable hydrogels, in particular, offer enhanced tissue and physiological adaptability, adjustable physical and chemical properties, low toxicity, good compatibility, and controllable degradation performance [9; 10; 11; 12; 13]. When used in drug delivery systems, injectable hydrogels enable localized drug release at the target site, thereby improving therapeutic outcomes and reducing systemic side effects [14; 15; 16]. Cellulose, rich in hydroxyl groups and hydrogen bonds [17; 18; 19], possesses excellent mechanical strength and properties. Cellulose hydrogels are advantageous for their hydrophilicity, biodegradability, biocompatibility, transparency, low cost, and non-toxicity [20], making them valuable for oral, ocular, and topical drug delivery systems [21]. Chitosan, a natural cationic polysaccharide with favorable biocompatibility and degradability, is an ideal material for hydrogel preparation [22; 23; 24]. Acetylated cellulose acetate (CAA), a derivative of cellulose acetylated with acetoacetic acid, features highly reactive acetyl groups that can form stable dynamic enamine bonds with amino groups under mild conditions [6; 7; 14]. The introduction of acetoacetyl groups into natural polymers significantly enhances the modification of polysaccharides and expands research possibilities.  
In this study, water-soluble cellulose acetate acetoacetate (CAA) with dynamic enamine bonds was synthesized under mild conditions and cross-linked with chitosan to prepare CAA-CS polysaccharide hydrogels with a three-dimensional network structure. The morphological characteristics were analyzed by scanning electron microscopy, and rheological analysis was conducted to evaluate mechanical properties and stability. Under simulated physiological conditions, IL-2 was encapsulated, and the drug encapsulation rate, release rate, and biocompatibility were evaluated [25].