Natural components, including biopolymers and bioactive compounds isolated from different natural resources, such as plants, animals, and microbes, have been widely used for biomedical applications [1,2]. A wide range of bioactive molecules and phytochemicals have been used to treat several types of diseases such as diabetes, chronic inflammation, skin infections, ulcers, metabolic deformities and specifically targeting abnormal cell growth in cancer. Quercetin is a natural polyphenolic component or flavonoid classified as a phytoestrogen of biochemical origin. It is also known as vitamin P because of its wide availability in primary natural dietary sources, such as red onion, red grapes, tea, green leafy vegetables, apples, and citrus fruits [3]. A potent flavonoid inhibits the activity of several enzymes such as acetylcholinesterase and cyclo-oxygenase. Moreover, these flavonoids possess antioxidant, anti-inflammatory, anticarcinogenic, anti-thrombin, anti-hypertensive, antiviral, and antibacterial activity [4,5]. Therefore, quercetin has been widely used as a therapeutic drug molecule to treat cancer, heart disease, and UV-induced damage [6,7].The poor solubility and degradation of the Quercetin molecule during the local administration inside the host body reduce its therapeutic potential and efficiency [8]. The drug delivery system, i.e., biocompatible, biodegradable, controlled drug release, showed the prolonged effect of the drug with maximum therapeutic index and reduced the side-effects [9,10]. 3D matrices fabricated from polymers and composites are widely used as a model to study drug release profiles, in vivo tissue–drug interactions, and targeted drug delivery systems [11,12]. Hence, quercetin is efficiently loaded in the different polymeric systems and studied for its effect on the therapeutic index [13,14,15].Different polymers have been studied and used as carriers for quercetin to enhance its therapeutic activity. Micro-emulsions of quercetin were prepared for the local administration of the drug molecule to study their effects under in vitro and in vivo animal systems to prevent UV-induced skin damage [16,17]. Fahlman and Krol reported that the plants and animal tissue treated with quercetin resist UV-induced mutations, and after the UV treatment, the Quercetin molecules slowly decompose into the non-toxic products [18]. Dias et al. fabricated quercetin-impregnated N-carobxylbutyl chitosan and agarose films for sustained release profiles and faster wound healing [19]. Natarajan et al. synthesized quercetin-containing polycaprolactone (PCL)–gelatin microspheres, coated with collagen to enhance the bio-adhesion of the microsphere and to prolong control drug release [20]. Another polymeric drug delivery system, polyethylene glycol (PEG)-12-hydroxy stearate, also improved the solubilization of quercetin up to five times [21]. Several studies reported that nanoemulsion as a drug delivery system increased the bio-accessibility of drugs. Pool et al. also reported that quercetin in nanoemulsions showed better bio-accessibility when compared to crystalline quercetin [22]. Wang et al., 2016, fabricated quercetin-loaded nanoliposomes (QUE-NLs) to study apoptotic cell death of cancerous tissue at a low concentration of 100 μM [16,23]. The polyvinylpyrrolidone (PVP)–quercetin composite microparticles were fabricated by coaxial electrospraying methods to enhance the solubility and infusion properties for oral or sublingual administration [24]. Polylactic acid (PLA) and polylactic co-glycolic acid (PLGA) are biodegradable and biocompatible polymers used to encapsulate and deliver the bioactive molecule Quercetin. Polymer-encapsulated Quercetin molecules strongly induced apoptosis of cancer cells [25].Physical entrapment of bioactive molecules or drugs into the biopolymeric matrices provides a biocompatible, bio-accessible, controlled drug-delivery system. The loading or entrapment of biomolecules in polymeric matrices is usually done by mixing, immersion, and physical adsorption [26]. Three-dimensional (3D) polymeric foam scaffolds are the simplest and cheapest extracellular matrix (ECM)–biomimetic matrix used for tissue engineering studies [27]. The various natural high foam-generating polymers, such as alginate, gelatin, and silk, were used to form foam scaffolds, with or without surfactant [28].Alginate is a polysaccharide isolated from seaweed, commonly used as a biopolymer, and has a more comprehensive application. Alginate has good mechanical and foam stability but poor surface functionality for cellular adherence, which limits its applicability [29]. In recent studies, different types of polymeric blends and composites of alginate with other polymers and non-polymeric components were designed to overcome the abovementioned limitations of alginate [30,31].Correspondingly, gelatin is hydrolyzed from collagen protein, having a short peptide Arg–Gly–Asp (arginine–glycine–aspartate) sequence, which helps in cell attachment and proliferation [32]. It is biocompatible, biodegradable, and one of the most potent clinically approved biomaterials. In earlier studies, to overcome the limitation of both natural polymers, alginate and gelatin blends were used to fabricate polymeric matrices or scaffolds, having significant biocompatibility due to the presence of gelatin short peptides and improving biomechanical strength of alginate [33,34,35].Therefore, gelatin and alginate are used as a polymeric matrix for the entrapment of drugs and bioactive components to improve their shelf life and enhance activity and efficiency under in situ conditions [33,36,37]. Pindolol-loaded alginate–gelatin polymeric cross-linked beads fabricated by solvent-free techniques showed the controlled release of pindolol with improved retention within the bead’s matrix [38]. Subsequently, alginate–gelatin microsphere beads were designed for the controlled release of endosulfan [39].

In this study, we fabricated a Quercetin-loaded biopolymeric foam scaffold to protect the therapeutic compound during passage through the body as a carrier and mediator/activator of controlled release. Here, we used alginate–gelatin foaming used for the entrapment of the quercetin as a polysaccharide–protein porous matrix for the drug-delivery system and a tissue-engineered scaffold for better cell signaling. Subsequently, the combination of polysaccharide and protein molecules enhances the drug encapsulation and release efficiency. However, quercetin, as a bio-active molecule, protects the healthier cell from oxidative damage and enhances cell growth, and the synergistic effect of polymeric components with quercetin could enhance the biocompatibility and anti-inflammatory and anti-oxidative effects.