Nanoemulsion-based pseudopolyrotaxane hydrogel for enhanced corneal bioavailability and treatment of corneal inflammation.

Corneal inflammation, a condition that can potentially lead to blindness, is often treated with topical eye drops. However, the limited ocular drug bioavailability of the eye drops necessitates frequent dosing. Herein, a nanoemulsion-based pseudopolyrotaxane hydrogel was fabricated to improve corneal bioavailability and thereby suppress inflammation. In this approach, dexamethasone was encapsulated into a nanoemulsion emulsified by Tween 80. The nanoemulsion was then mixed with γ-Cyclodextrin (γ-CD) aqueous solution to produce dexamethasone-loaded nanoemulsion-based pseudopolyrotaxane hydrogel (DEX-NPH) via host-guest interaction between Tween 80 and γ-CD. The hydrogel exhibited a shear-thinning and thixotropy character. In vitro drug release and hydrogel dissolution studies showed that drugs released from hydrogel predominantly in the form of nanoemulsion. The ocular surface fluorescence imaging and tear pharmacokinetics indicated that the hydrogel could significantly prolong precorneal residence time. The corneal pharmacokinetics suggested that DEX-NPH with 35 % γ-CD improved corneal bioavailability by 1.29-fold compared with nanoemulsion and by 4.09-fold compared with free drug solution. In particular, the precorneal retention capacity and corneal bioavailability could be adjusted by changing the γ-CD content in the hydrogel. Moreover, ocular irritation evaluation confirmed the excellent safety of such hydrogel. In an alkali burn-induced corneal inflammation model, the hydrogel exhibited a superior anti-inflammatory effect compared to nanoemulsion or free drug solution alone. In summary, the nanoemulsion-based pseudopolyrotaxane hydrogel is promising for enhancing corneal bioavailability and treating corneal inflammation.