An injectable hydrogel based on hyaluronic acid prepared by Schiff base for long-term controlled drug release

Abstract

Drug-loaded injectable hydrogels have been studied widely in biomedical technology while the stable long-term controlled drug release and cytotoxicity are challenges. In this work, an injectable hydrogel with good swelling resistance was in situ synthetized using aminated hyaluronic acid (NHA) and aldehyde β-cyclodextrin (ACD) via Schiff base reaction. The composition, morphology and mechanical property were characterized with FTIR, 13C NMR, SEM and rheology test, respectively. Voriconazole (VCZ) and Endophthalmitis was selected as a model drug and disease, respectively. The drug release, cytotoxicity and antifungal properties were detected in vitro. The results showed a long-term (> 60 days) drug release was realized, the NHA/ACD2/VCZ presented a zero-order release in the later stage. The cytotoxicity of NHA/ACD was detected by live/dead staining assay and Cell Counting Kit-8 (CCK-8). The survival rate of adult retina pigment epithelial cell line-19 (ARPE-19) was over 100 % after 3 d, it indicated a good cytocompatibility. The antifungal experiment presented samples had antifungal property. Biocompatibility in vivo proved NHA/ACD2 had no adverse effects on ocular tissues. Consequently, the injectable hydrogel based on hyaluronic acid prepared by Schiff base reaction provides a new option for long-term controlled drug release in the course of disease treatment from a material perspective.