Oxidized cyclodextrin-functionalized injectable gelatin hydrogels as a new platform for tissue-adhesive hydrophobic drug delivery

摘要

A practical approach toward developing dual-functional hydrogels with high adhesiveness and hydrophobic drug delivery is described. An additional Schiff base reaction was introduced into a phenol–phenol crosslinked gelatin hydrogel to markedly increase adhesiveness. Oxidized β-cyclodextrin (oβ-CD) functionalized with aldehyde groups and possessing a hydrophobic cavity was exploited as a crosslinker in the Schiff base reaction to solubilize the hydrophobic drug. Simply blending gelatin–tyramine (GTA) and oβ-CD in the presence of horseradish peroxidase (HRP)/H₂O₂ rapidly and controllably formed GTA–oβ-CD hydrogels in situ. The optimal composition of GTA–oβ-CD hydrogels was found to be 5 wt% GTA (GTA5) with 1 wt% oβ-CD. Their adhesiveness was 2.3- and 6.2-fold higher than those of GTA-only hydrogels and fibrin glue, respectively. Their elastic modulus and degradation rate were 1.8- and 1.5-fold higher than those of GTA hydrogels owing to additional imine bonds. Hydrophobic drugs (dexamethasone and curcumin) could be dissolved homogeneously in GTA–oβ-CD matrices with greater loading efficiencies than in GTA matrices. An in vitro test of cell viability using human dermal fibroblasts demonstrated that GTA–oβ-CD hydrogels were cytocompatible. In summary, dual-functional injectable GTA–oβ-CD hydrogels can be used as a promising platform to improve tissue adhesion and hydrophobic drug delivery.