Mechanoresponsive Drug Loading System with Tunable Host–Guest Interactions for Ocular Disease Treatment

Conventional administration of eye drops often requires high dosages and/or repetitive treatments to achieve therapeutic efficacy. This is inefficient and may result in side effects or even toxicity. Although many delivery systems of ophthalmic drugs have been reported, most of them work in a fixed format in which both the type and dose of the loaded drugs cannot be changed upon demand. To overcome this limitation, a hybrid double network hydrogel system composed of methacryloyl gelatin, pluronic F127 diacrylate, and β-cyclodextrin-modified oxidized dextran was developed. The hydrogels presented good mechanical strength and biocompatibility. In vitro assessments demonstrated that the hydrogels loaded with commonly used ophthalmic drugs could sustain the drug release for more than 21 days. This hydrogel system exhibited features of mechanoresponsive drug loading, and the capacity of drug loading could be significantly enhanced by macroscopically mechanical compression. Further in vivo evaluation of the drug delivery capacity showed that a dexamethasone-loaded hydrogel as a fornix insert effectively suppressed upregulation of proangiogenic factors and suture-induced corneal neovascularization in rats. This novel hydrogel system represents a promising drug delivery platform, which could potentially improve the treatments of ocular surface and other diseases.