Next-Generation Hydrogels as Biomaterials for Biomedical Applications: Exploring the Role of Curcumin

Since the first report on the pharmacological activity of curcumin in 1949, enormous amounts of research have reported diverse activities for this natural polyphenol found in the dietary spice turmeric. However, curcumin has not yet been used for human application as an approved drug. The clinical translation of curcumin has been hampered due to its low solubility and bioavailability. The improvement in bioavailability and solubility of curcumin can be achieved by its formulation using drug delivery systems. Hydrogels with their biocompatibility and low toxicity effects have shown a substantial impact on the successful formulation of hydrophobic drugs for human clinical trials. This review focuses on hydrogel-based delivery systems for curcumin and describes its applications as anti-cancer as well as wound healing agents.


INTRODUCTION
1.1. Hydrogels. Hydrogels are three-dimensional crosslinked polymeric networks with the ability to absorb water due to the presence of hydrophilic functional groups in their structure. 1,2 This hydrophilic property enables hydrogels to absorb water tens to thousands of times of their dry weight. 3,4 Hydrogels can be classified into two main categories including chemically or physically cross-linked networks. 5 Chemically cross-linked hydrogels consist of a polymeric network with covalent bonds making them stable during swelling while physically cross-linked hydrogels degrade and dissolve during the water absorption due to the presence of noncovalent, reversible interactions in their polymeric network. 5,6 Synthetic and natural-derived polymers can be used to prepare hydrogels. 7−9 The source of these polymers determines several characteristics of hydrogels including their capacity for water absorption, mechanical properties, degradation behavior, and half-life in biological media. 10,11 Despite significant advantages of natural-derived polymers to make hydrogels, great attention has been directed to synthetic polymers. 12 This is the result of various parameters including enhanced mechanical characteristics and degradation of hydrogels in a finely tuned, highly controlled manner. The most frequently investigated natural polymers used for hydrogel preparation are chitosan, dextrin, lignin, hyaluronic acid, carrageenan, tannic acid, alginic acid, and collagen. 13−20 Synthetic and semisynthetic polymers can also be used for hydrogel preparation. 21 These polymers mainly include polyethylene glycol (PEG), poly lactic acid, poly lactic coglycolic acid (PLGA), and poly vinyl alcohol (PVA) as well as carboxymethyl cellulose (CMC), hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose. 21−29 Based on the monomers used for the preparation of the polymeric network, hydrogels may contain homo-polymeric, co-polymeric, or multi-polymeric networks. 30,31 While polymerization of a single type of monomers results in the formation of homo-polymeric networks, copolymeric or multi-polymeric networks result from the polymerization of two or more types of monomers. 32,33 The biocompatibility, swelling behavior, and low toxicity of hydrogels make them suitable candidates for biomedical applications including drug delivery. 34−37 One of the major obstacles for drug development is the administration of hydrophobic drugs with low solubility in aqueous media. 38 Considering the unique properties of hydrogels, this delivery system can be used as a promising vehicle for formulation of low soluble hydrophobic therapeutics. 21,39,40 This approach enables researchers and patients to apply these therapeutic agents via oral, topical or parenteral routes of administration. 41 1.2. Curcumin. Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3methoxyphenyl)-1,6 heptadiene-3,5-dione) is a bright yellow polyphenol extracted from the roots of Curcuma longa species. 42 From ancient days, it has been using in Asian food and traditional medicine. 43 As earlier defined, two chemical units (2 o-methoxy phenol) of the molecule are connected by a seven-carbon linker with an α,β-unsaturated diketone moiety. 44,45 Curcumin acts as an electron donor, and the π electron cloud stabilizes its chemical structure. The resonance structure exhibited inside the molecule is responsible for its contribution to many electron transfer reactions. 46,47 Lampe first described the procedure for the synthesis of synthetic curcumin in 1913. 48 Later on, several scientists developed methods for high yield synthesis of curcumin which are in use today. 49 Curcumin is the most widely used plant-based drug with various pharmacological benefits, including anti-inflammatory, antioxidant, anti-viral, anti-bacterial, anti-fungal, antiparasite, and anti-cancer. 50−59 Numerous preclinical studies have proven curcumin to be effective in several cancers because of curcumin's capability to induce G2/M cell cycle arrest, trigger apoptosis, induce autophagy, disturb molecular signal-ing, inhibit invasion and metastasis, and increase the efficiency of existing chemotherapeutics. 60,61 The inflammatory response of curcumin is often steered by the radical production of proinflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). 62,63 Consequently, the downregulation of pro-inflammatory cytokines may effectively reduce the incidence of inflammation. 64 Curcumin is also involved in other signaling pathways like it induces degranulation in human neutrophils by increasing the cell surface expression of clusters of differentiation 35 (CD35), CD66b, and CD63. 65 However, its clinical usage is limited due to its low bioavailability and poor water solubility. 43,66,67 Further, curcumin utilization in food supplements and nutraceutical products is challenging due to its high chemical instability. 68 Curcumin shows a tendency to crystallize in aqueous acidic conditions and is unstable to chemical degradation in basic aqueous conditions, which is attributed to changes in the molecular structure of curcumin. 69  78−86 The biological activity of curcumin was first reported by Schraufstaẗter and Bernt, where they showed the anti-bacterial activity of the compound against Staphylococcus aureus. 87 Despite promising biological properties, low cost, and availability in bulk, a limited number of human clinical trials have been reported for curcumin and its derivatives. 68,88 The major challenge for human application of curcumin is its poor bioavailability resulting from low solubility and stability. 61 Following the administration of substantial doses of curcumin, its plasma level becomes negligible within hours. 89,90 Considering the unique properties of hydrogels, they can improve the bioavailability, solubility, and stability of curcumin for medical applications 48,64,91−96 (Table 1). This delivery system also provides the opportunity to be decorated with specific targeting ligands directing the payload to the precise site of action. 97,98 This leads to the reduction of side effects while it increases the pharmacological activity in the target site. 99 Moreover, stimuli-responsive hydrogels provide the opportunity to transfer the payload in a highly controlled manner. 100 Furthermore, the use of hydrogel as a vehicle for curcumin delivery enables researchers to apply the drug via different routes of administration such as oral, topical, nasal, or parenteral ways. 101,102 Since various pharmacological activities have been reported for curcumin (e.g., anti-cancer, wound healing, anti-inflammation, and antimicrobial), preparation of diverse formulations for different routes of administration may facilitate their bench to bedside translation. 12,103,104

CURCUMIN-LOADED HYDROGELS FOR CANCER THERAPY
Curcumin can influence a variety of cell signaling pathways and negatively affect cancer cells; 123 for example, it inhibits vascular endothelial growth factor (VEGF) and its receptor VEGR-2 and fibroblast growing-factor 2 (FGF2) and downregulates matrix metalloproteinases (MMPs) 2 and 9 ( Figure 1). 124,125 Since the epithelial-mesenchymal transition (EMT) plays a significant role in cancer invasion and metastasis in epithelialderived cancers, curcumin might represent a promising therapeutic agent in human hepatocellular carcinoma by inhibiting the transforming growth factor-β1 (TGF-β1)induced EMT in liver cells ( Figure 1). 98,126,127 There are several approaches to improve the solubility and stability of curcumin, including encapsulating curcumin in lipid carriers and binding to nanoparticles (NPs). 68,128 As of late, a complex series of nanotechnology and polymer biomaterials have spoken to the development of more common golden methods. 129 Nanoformulations are used as curcumin delivery systems including polymeric NPs, liposomes, hydrogels, nanoemulsions, nanofibers, lipid transferors, and membranes of polymer mixtures. 61,130,131 The advanced curcumin delivery system can increase efficiency, solubility, and bioavailability as well as raising blood half-life, and reduce deterioration rate. 132 Currently, a mixed synthetic and natural polymer hybrid nanocomposite hydrogel film is introduced as a new drug delivery method for biomedical applications This system is mainly used for cancer diagnosis and treatment due to its satisfactory spontaneous properties and biological compatibility, low cost, and the sustained release of the biological materials (Table 2). 133,134 Various recently developed curcumin-loaded hydrogels have been made known with great therapeutic effects in cancer treatment. 135 Here, some of the main types of curcumin-loaded hydrogels used for cancer therapy are discussed.
2.1. Curcumin-Loaded Injectable Thermo-sensitive Hydrogels. Injectable thermo-sensitive hydrogels display a sol−gel phase transition upon injection in rejoinder to temperature and have been known as an attractive drug delivery system which provides high local drug concentration, sustained release, and low systemic toxicity. 136,137 The gelation mechanism of injectable hydrogels is further categorized into chemical and physical cross-linked hydrogels. 138 There are also several injectable curcumin hydrogels developed for effective cancer therapy. For example, to promote the water solubility and bioavailability of curcumin, it is encapsulated in liposome (Cur-Lip). A curcumin liposome hydrogel (CSSH/Cur-Lip Gel) is formed through the biochemical cross-connection of free thiol groups and thermoregulation during the addition of β-glycerol phosphate, which can be used as an injectable hydrogel ( Figure 1). The liposome hydrogel can modify the dose, form, size, and release profile and reduces the side effects of drugs. The injectable, in situ formable, as well as thermosensitive curcumin and chitosan thiol coated liposome hydrogel is designed as a promising drug carrier for sustained local drug delivery. This system can also transfer a high concentration of drugs constantly to minimize burst release and suppress breast cancer reappearance both in vitro and in vivo. Curcumin prevents MCF7 cell proliferation in a dose-/ time-dependent manner. 139 In a study, a curcumin-encapsulated injectable thermoreversible self-assembled supramolecular hydrogel was developed for sustained release of curcumin and enhanced antitumor activity in vivo. 140 Sarika et al. also developed a gelatin-based curcumin-loaded nanogel for breast cancer therapy. 141 As shown in Figure 2, Ning et al. developed a novel strategy based on injectable hydrogels to enhance drug encapsulation efficiency and increase localized drug concentration. They used a thiolated chitosan (TCS) and poly-(ethylene glycol) diacrylate (PEGDA) to develop these hydrogels. Further, lysozyme was introduced into the system to enhance its antitumor activity. 142

Curcumin-Loaded Peptide Hydrogels.
The developing field of peptide-based hydrogels makes the available material definition and design appropriate for future clinical biomedical endeavors and provides new scaffolds for drug delivery and tissue engineering. 143,144 Peptides tend to be amphiphilic and depend on intramolecular folding as well as physical intra-and intermolecular interactions. The major advantages of using synthetic peptides are the easy introduction of alterations into the hydrogel scaffold through amino acid addition or substitution, shortening/extension of the peptide sequence, and functional epitope addition at the termini of peptide chains or as side chains to a peptide sequence. 145 For example, the healing effect of a self-assembled peptide hydrogel used for continuous delivery of doxorubicin and curcumin was evaluated in head and neck tumor cells. 146 The codelivery system showed superior apoptosis-associated cell reaction and led to the stop of cells in the S and G2/M phases ( Figure 1). 146 In a study, the curcumin-loaded selfassembling peptide hydrogel was developed as an effective localized delivery system of curcumin over sustained intervals. 147 Yang et al. also developed a RADA16-I peptidebased hydrogel to introduce curcumin and paclitaxel into tumors. RADA16-I is a nanofiber scaffold derived from selfassembling peptide RADA16-I, which is widely used in regenerative medicine and tissue repair. 148 2.3. Curcumin-Loaded Polymer-Based Hydrogels. Polymers such as poly(vinyl alcohol) have shown proper film-forming properties due to the abundance of OH groups in their structure. 149 According to El-Nashar et al.'s study, poly(vinyl alcohol) and curcumin, as a composite film, can be used for liver cancer. 150 The curcumin-loaded film can be used as a promising delivery system against breast and liver cancers. Thanks to the incorporation of cellulose nanocrystals (CNCs), the objective was fulfilled by improving the encapsulation efficiency and maximizing the efficacy of loaded curcumin through a sustained release profile. Curcumin showed a slow release profile leading to improved bioavailability and prevented rapid metabolism and clearance from blood. 151 Polyethylene glycol D-α-tocopheryl succinate 1000 (TPGS) is a water-soluble formulation derived from vitamin E that acts as a surfactant. This material is able to form micellar NPs in water. 152 Delivery of curcumin using this system resulted in a slow release of the drug and showed substantial effects on decreasing ROS concentration and developing apoptosis of HT-29 colon cancer cells in vitro. In addition, it seems that the bioavailability of oral curcumin formulation by TPGS can be increased compared with free curcumin. 132 A promising new approach to overcome the hydrophobicity of curcumin is the application of injectable thixotropic hydrogels made from silk fibroin/hydroxyl propyl cellulose. In vitro and in vivo drug release and cytotoxicity studies showed long-term sustained antitumor effects compared to the free drug or single drug-loaded hydrogel formulation. 152 Polymeric micelles are commonly used as drug delivery systems to overcome the low solubility of hydrophobic drugs. 153 Encapsulated into polymeric micelles, hydrophobic drugs form stable water-based formulations used for intravenous or intraperitoneal applications. In vitro tests suggest that the hydrogel system can release curcumin in a controlled manner. In addition, curcumin hydrogels can significantly suppress tumor growth and metastasis in a mouse model of colorectal and peritoneal carcinomatosis. Furthermore, curcumin hydrogels suppressed proliferation, induced apoptosis, and reduced angiogenesis of tumors. 154 In order to develop a liver-targeted delivery system for curcumin, 155 glycyrrhetinic acid was employed to prepare supramolecular curcumin pro-gelator (GA-Cur). The targeted delivery system showed continuous release of the drug from the formulation through hydrolysis of the ester bond. GA-Cur is a promising targeted approach for hepatic delivery of curcumin. 156 Many other types of curcumin-loaded hydrogels are listed in Table 2. In summary, curcumin-loaded hydrogels demonstrated excellent improvement in the therapeutic effects in various cancers with diminished side effects.

CURCUMIN-LOADED HYDROGELS FOR WOUND HEALING
Wound healing consists of three phases including inflammation, proliferation plus the formation of granulation tissue, and medium formation and conversion. 78,168−171 Curcumin represses the action of the inflammatory transcript factor NF-κB, which is responsible for controlling several genes involved in the initial onset of the inflammatory reaction. 172 Curcumin effectiveness for wound healing has been limited in the clinical trials due to its poor solubility and fast metabolism as well as low uptake and poor pharmacokinetic properties and bioavailability. 168,173,174 Various biopolymers for the delivery of curcumin have been investigated, including chitosan, starch, zein, alginate, and silk. 172,175 These systems have shown various characteristics including biodegradability and biocompatibility, as well as a wide range of commercial applications, making them ideal candidates for drug delivery applications. 176 These unique properties allow drugs or cells to be simply combined into aqueous polymer solutions via simply mixing and then adding the formulations into target tissue to form a gel in situ to act as a drug delivery system. 177 Poor water solubility of curcumin and its low bioavailability restrict its applications. To overcome these limitations, encapsulating curcumin in a hydrogel network is a helpful strategy. 178 The formation of an absorbent hydrogel is important for wound healing since it provides oxygen and stores large amounts of water. 174 In addition, a thin layer of hydrogel on the wound surface protects it from air damage. 168 Lack of moisture in wound surroundings is a problem in stimulating the perfect wound healing process. 179 Therefore, the humid environment provided by the hydrogel helps skin regeneration. In addition, hydrogels absorb growth factors and cytokines from plasma or wound exudate and promote cell proliferation and relocation besides their angiogenesis to enhance wound healing (Figure 3). 168 Hydrogels are perfect dressings for extremely damaged orthopedic injuries or surgeries, as they can incorporate medications and growth factors that accelerate wound healing. 180 Below, there are some examples of research on curcumin-loaded hydrogels and other healing materials (Table 3). Several studies have also been conducted to improve wet dressings to overcome the deficiencies of dry dressings and improve soft tissue repair. 181 Classification is summarized according to various functional aspects of curcumin-loaded hydrogels including anti-inflammatory, antibacterial, and angiogenesis promotion.
3.1. Anti-inflammatory and Antioxidant Effects of Curcumin-Loaded Hydrogels in Wound Healing. Chitosan-pluronic P123-curcumin-gelatin is a promising candidate for the development of injectable hydrogels designed for wound healing. 182 Chitosan hydrogel is useful for wound healing. 183 Chitosan can be conjugated to a cross-linking agent through its amine functional groups to form a threedimensional hydrogel system. 184 Curcumin-loaded chitosan NPs (167−251 nm) showed higher tightening efficiency, significant transdermal permeability, enhanced drug release, and high cell viability for transdermal application. 185 The swelling behavior of the dual loaded hydrogel was more than 1.2 times that of the gelatin-free hydrogel. This system increases the water absorption with mixed gelatin. 186 Since gelatin is dispersed throughout the polymer grid and acts as a cell glue 182 and the antioxidant properties of curcumin can provide additional assistance for wound dressings, 187 chitosan-P123 nano curcumin-gelatin showed enhanced wound dressing properties compared to single loaded hydrogels. This injectable, biocompatible, biodegradable, and thermo-reversible hydrogel can be used as optimal promising biomaterial for controlled drug delivery, tissue restoration, or other therapeutic applications. 182 A curcumin and 2-hydroxypropyl gamma ring-shaped cyclodextrin (Cur/HP-γ-CDS) complex in a Sacran hydrogel film (Sac-HGF) shows the highest wound healing capability in nude mice due to the increased solubility of curcumin and its antioxidant action. Therefore, Sac-HGF can be used as a candidate biomaterial for wound dressings. 188 Loading curcumin into amphiphilic alkylated cerium oxide NPs improved its bioavailability and use at the wound location. These NPs show improved bioavailability and antioxidant properties. The hydrogel has multiple properties, illustrates continuous drug release (approximately 63% in 108 h), accelerates cell movement, and provides a remarkable antioxidant and anti-inflammatory activity in vivo (approximately 39%). NPs and NP-loaded hydrogel systems showed potential antioxidant effects and increased cell migration. Furthermore, the results of the protein reactivity of carrageenan as a model for inflammation showed the development of effective anti-inflammatory effects of NPs which can be considered as candidates for wound healing. 189 The honey-curcumin hydrogel sponge can be formulated by easy addition and in situ polymerization. Due to its high fluid absorption capacity, the hydrogel matrix provides a dry wound area. Chitosan and honey contribute to faster wound healing. The prepared sponge is highly flexible and has fine mechanical strength. It permits low penetration of moisture and shows controlled diffusion of curcumin. 190 Wounds healed with micellar curcumin-loaded thermo-sensitive hydrogel (Cur-MH) showed significant dehydration with no sign of pathological fluid leakage commencing the wound. In summary, compared to the normal saline-treated wound (NS treatment), the wound had no sign of inflammation or infection. In vitro experiments show that Cur-MH compound gel exchanges at about body temperature. Follow-up in vivo experiments found Cur-MH effective in rats. In full-thickness in line cut and removal wound models, it has a good effect. 179 Researchers developed a curcumin-loaded nanoemulgel (Cur-NEG) through high-energy ultrasonic emulsification to improve wound healing in vivo. They used a minimum concentration of surfactant to prepare nanogels. 191 As shown in Figure 4, the results demonstrated that Cur-NEG showed complete wound healing in Wistar rats. The authors used a conventional curcumin gel as a control.

Angiogenic Effect of Curcumin-Loaded Hydrogels in Wound
Healing. Curcumin nanomicelles can prevent curcumin degradation. Curcumin nanomicelles combined with dextran hydrogel are used to enhance continuous release of curcumin from hydrated dressings in order to reduce inflammation, promote fibroblast proliferation and collagen synthesis, as well as promote full-thickness wound healing and improve angiogenesis (Figure 2). 192 The nanocurcumin-loaded hydrogel can effectively improve wound healing by enhancing early the re-epithelialization process. Various properties of procurcumin and nanocurcumin hydrogels on wound healing can be elucidated by in vitro firmness examinations. 193 In addition, collagen deposition in the wound was stained with Masson's Trichrome, indicating that N,O-carboxymethyl chitosan/ oxidized alginate hydrogel (CCS/OA) can effectively improve collagen deposition in granulation tissue. Nanocurcumin/ CCS/OA hydrogel therapy significantly increases DNA and protein content in the wound tissue, indicating frequent cell Table 3. continued  221 proliferation in the wound tissue as a result of promoted wound healing. 194 In-situ-forming hydrogels (ISGs) are usually fluid liquids, and as they come into contact with physiological surroundings such as ions, pH, and temperature, they suddenly turn into gels. 195 In-situ-forming hydrogels can completely cover the wound area. 196 In an investigation, the curcumin-phospholipid complex (CPC) was prepared by the interaction between the choline-containing phospholipids (CCPLs) and the hydroxyl groups of curcumin. In this study, in vitro tests showed suitable curcumin release. CPC-ISG significantly improved the epidermis healing, which is quite significant for primitive skin formation. 168 Recent studies show that curcumin NPs have a substantial effect on the formation of new blood vessels and endothelial cells, which accelerate wound healing. 186 This develops organized deposition of collagen plus VEGF synthesis and expression of Aquaporin-3 in diabetic wounds. 197 To extend the method for efficient and safe affixing wound healing in diabetics, a thermoresponsive hydrogel containing nanomedicine, loaded in gelatin microspheres (GMs), was designed and developed to transport curcumin as a wound healing agent. 186 Curcumin was then joined to shape self-assembled nanoparticles (CNPs) using reprecipitation to improve its solubility and stability. CNPs, coated with GMs, might be able to react with matrix metalloproteinase 9 (MMP-9), which is often overexpressed and persists at the site of non-healing skin lesions in diabetes. 198 As a result, the skin recovery process demands an equilibrium between the collagen breakdown and the production of new components of the extracellular matrix, 199 as determined by substrate MMP and tissue metalloproteinase inhibitors. 186 3.3. Antibacterial Effect of Curcumin-Loaded Hydrogels in Wound Healing. The main cause of delayed wound healing is the infection of a wound due to bacterial growth around the wound. Therefore, it is essential to design hydrogels with high antibacterial activity. 200 As shown by the curcumin hydrogel formulation by PVA, the hydrogel has great antibacterial efficacy compared to the PVA hydrogel alone. The designed curcumin-PVA hydrogel has shown increased antibacterial activity with increasing curcumin concentration. This hydrogel formulation was tested against S. aureus and E. coli. 174,201 Gelatin hydrogel dressings are made of ion-adapted self-organized bacterial cellulose extracted from Glucanoacetobacter xylinus. The curcumin-loaded membranes were capable of diminishing the growth of Gram-positive and Gram-negative bacteria. This was also shown by the morphological study of living and dead bacteria and by fluorescence color analysis. 202 Several similar curcumin hydrogels are studied in wound healing applications. 203−205 Various wound healing applications of curcumin-loaded hydrogels are listed in Table 3.

CONCLUSIONS
Curcumin has an outstanding safety profile among all the nutraceuticals with numerous pleiotropic biological activities such as anti-inflammatory, antioxidant, and anti-cancer effects. It is a readily available, low-priced compound that can cross the BBB and is helpful for neurodegenerative diseases. Its pharmacological properties are becoming more interesting recently as the applications of curcumin are a fast-growing, improving, and escalating enterprise, as evidenced by the studies. Curcumin exhibits a variety of pharmacological activities as evidenced by its uses in many diseases like cancer, diabetes, wound healing, arthritis, Alzheimer's, Parkinson, inflammation, angiogenesis, atherosclerosis, hypertension, etc. Curcumin is enriched with many valuable phytoconstituents, which are responsible for its efficacy and are proven experimentally and clinically. 57 It has been recognized as beneficial in treating anti-inflammatory, anti-allergic, antioxidant, anti-hyperglycaemic, anti-cancer, antimicrobial, antiatherosclerosis, and anti-hypertension properties. Curcumin's ability to affect a large variety of molecular targets and its good safety profile established it to be a potential candidate for the treatment of many diseases. Over the decade curcumin received extensive consideration due to advances in its potential therapeutic applications. Nevertheless, clinical applications of curcumin are minimal due to its poor solubility and bioavailability. To overcome these problems, the development of specific curcumin-encapsulated nanocarriers (nanocurcumin) has tremendous interest and enhances its applications. With detailed literature investigation, nanocurcumins, including curcumin hydrogels, improve the pharmacokinetic properties of curcumin that offer better therapeutic value. So far, many hydrogels mediated nanocurcumin and other nanocurcumins, studied for the proof of concept only. Very few clinical studies of nanocurcumins have been conducted, which showed favorable features such as bioavailability and retention time compared to curcumin alone and systemic safety. Still, there is a significant gap in the research field to assess the safety and efficacy of nanocurcumin formulations in humans. It requires thoughtful and dedicated research efforts. We believe that our present review article on hydrogel-based nanocurcumins will give detailed information on recent updates to the audience and be helpful for future developments.