Table 5.

Potential application of chemically cross-linked CD-containing hydrogels.

No.	Drug	Formation Materials	Hydrogel State	Types of Cell	Summary	Potential Application	Ref.
1	5-Fluorouracil	β-CD; N-vinylcaprolactam; N, N′-methylene bisacrylamide	Nanogel	Human colon cancer cell lines (HCT 116); MRC-5 normal cells	The hydrogel had the best drug loading (659.7 mg/g) after controlling the feeding ratio. The drug release curve showed that the hydrogel could continue to release drugs for up to 30 h; especially in the intestinal juice with pH = 7.4, the 5-fluorouracil drug molecules contained therein were not completely released; and the maximum release rate was 68%.	Implantable hydrogels	[93]
2	Coumarin	β-CD; alginate; calcium homopoly-L-guluronate	Supramolecular hydrogel	RAW 264.7 cells; T. cruzi cells	The lowest release of substituted amidocoumarins from the hydrogels occurred at pH = 1.2 whereas the maximum release (34%) was observed at pH 8.0.	Biomedicine	[94]
3	Curcumin	β-CD; epiclon	Nanosponge	Non-tumorigenic human breast; invasive mouse breast cell lines (4T1)	The high degree of cross-linking led to the formation of mesoporous having high specific surface area and high loading capacity. Nanosponge showed no toxicity against MCF 10A and 4T1 cells as normal and cancerous cells, respectively.	Cancer therapy	[95]
4	Curcumin	Carboxymethyl-β-CD; gelatin; methacrylic anhydride	Microneedle arrays	B16F10 melanoma cell	The inclusion complex of curcumin maintained 90% of the initial concentration. Besides, the hydrogel could enhance the drug loading and adjust release. In vivo study showed that hydrogel had good biocompatibility and degradability.	Transdermal drug delivery	[96]
5	Dexamethasone	β-CD; low-acyl gellan gum; EDC	Injectable hydrogel	NIH/3T3 mouse embryo fibroblast	After drug loading, the gel-forming temperature of the modified hydrogel was reduced and the mechanical properties are improved. Hydrogel had a high affinity and release rate for drugs. In vivo studies had shown that the drug-loaded hydrogel improved the anti-inflammatory response.	Tissue engineering and regenerative medicine	[52]
6	Dexamethasone	β-CD; sodium hyaluronate	Delivery hydrogel	3T3 cells	The novel hydrogels significantly improved the therapeutic effect of dexamethasone in burn wound healing.	Wound healing	[58]
7	Dexibuprofen	β-CD; acrylic acid; methylene bisacrylamide	Nanosponges	Not mentioned	The solubility of ibuprofen in the hydrogel was increased 6.3 times. In vitro release experiments demonstrated that the drug release rate of β-CD nanosponges reached 89% within 30 min under the condition of pH = 6.8.	Oral administration of lipophilic drugs	[97]
8	Diclofenac sodium	β-CD; sodium hyaluronan; EDC;	Contact lens materials	S. aureus; 3T3 fibroblasts	The hydrogel not only reduced the adsorption of tearing proteins due to electrostatic mutual repulsion but also improved encapsulation capacity and sustainable release of diclofenac (t > 72 h). In vitro cell viability analysis displayed that all hydrogels were non-toxic to 3T3 mouse fibroblasts.	Ophthalmic diseases	[66]
9	Doxorubicin	β-CD; 2-ethyl-2-oxazoline; aminopropyltriethoxy silane; FeCl2.4H2O; FeCl3.6H2O	Magnetic nanohydrogel	MCF7 cells	The magnetic nanohydrogel had a good drug loading rate (74%) and encapsulation rate (81%). Under acidic conditions (pH = 5.3), adding a small amount of GSH (10 mM) increased the release value (89.21%). The magnetic nanohydrogel had good cell compatibility even at high concentrations (10 mg/mL).	Implantable hydrogels	[98]
10	Doxorubicin	β-CD; agarose	Injectable hydrogel	Human embryonic kidney 239 cells; HeLa cells	The hydrogel was able to easily and uniformly load a drug at 30 °C. The drug-loaded hydrogel maintained the drug’s anti-cancer activity. In addition, the hydrogels did not exhibit toxicity toward the HEK-293 and HeLa cells.	Injectable hydrogel	[59]
11	Doxorubicin	β-CD; hyaluronic acid; bis(4-nitrophenyl) carbonate	Injectable hydrogel	Human colorectal cancer cells HCT-116	Rheological tests showed that this hydrogel could be easily prepared and used on a schedule compatible with normal operating room procedures. In vitro experiments showed that the unique physical and chemical properties of the hydrogel ensured the sustained release of anticancer drugs (t > 32 d) and prevented the growth of colorectal cancer micelles under 3D culture conditions.	Device for localized chemotherapy of solid tumors	[99]
12	Doxorubicin; curcumin	β-CD; multiwalled carbon nanotubes; maleic anhydride; folic acid; hexamethylene diisocyanate	Nanocarrier	Not mentioned	This injectable hydrogel exhibited pH/thermo response and exerted a deleterious effect on the tumor. A sustained release of the two drugs was observed over a period of 30 h. The release rate of doxorubicin reached 90% under tumor microenvironmental conditions, and the release rate of curcumin reached 85% under high temperature and physiological pH conditions.	Injectable nanocarriers	[100]
13	Doxorubicin	β-CD; tetronic; adamantane	Injectable shear-thinning hydrogels	HeLa cell	The hydrogels showed shear-thinning behaviors, rapid recovery properties, pH-responsive properties, and long-term release of the hydrophobic drug.	Embolic material	[101]
14	Insulin	Carboxymethyl β-CD; carboxymethyl chitosan	Microparticles	Caco-2 cells	The insulin was loaded into the hydrogel, and the results of the drug release experiment found that the insulin was successfully retained in the stomach environment and slowly released after passing through the intestine. In vitro studies had shown that the hydrogel particles exhibited non-cytotoxicity and were mainly transported in the Caco-2 cell monolayer through paracellular pathways.	Oral drug delivery	[102]
15	Vitamin E	β-CD; soy soluble polysaccharides; galacturonic acid	Core-shell bionanomaterials hydrogel	Not mentioned	The hydrogel exhibited significant swelling adsorption and sustained release (t > 230 h) for the release of vitamin E in vitro. The encapsulation efficiency and drug loadings were 79.10% and 16.04%, respectively. In addition, after oral administration of the vitamin E-loaded hydrogel in rats, the vitamin E level in the plasma continued to increase within 12 h.	Oral drug carrier	[56]