In situ forming gelatin: Cyclodextrin hydrogels prepared by “click chemistry” to improve the sustained release of hydrophobic drugs

Injectable hydrogels offer a wide range of attractive benefits in drug delivery applications, such as non-invasive administration, easy drug incorporation and locally controlled release at the target sites. Herein, we designed a simple and efficient method to prepare injectable hydrogels composed of gelatin and cyclodextrin (CD) for high loading capacity of hydrophobic drugs. The hydrogels were formed by thiol-functionalized gelatin (GSH) and βCD-vinyl sulfone (βCD-VS) as cross-linker, via thiol-ene “click” chemistry. Hydrogels comprising of different cross-linker feed amount were investigated in terms of their physico-chemical properties, such as gelation time, mechanical strength, swelling ratio, porosity and degradation rates. For the use as a drug delivery vehicle, dexamethasone (DEX), a commonly anti-inflammatory, immunosuppressive but poorly water soluble drug was chosen to show the high drug loading capacity and prolonged drug release of hydrogels. The drug release was found to be depended on the concentration of βCD-VS due to the drug-CD interaction. In vitro cytotoxicity experiment also showed the cell compatibility of these hydrogels against human dermal fibroblasts. In summary, we expect this gelatin-CD “click” hydrogel will be a promising candidate for localized and long-term delivery of hydrophobic drugs. Graphical Abstract