Niosomal in situ gel enhances the ocular bioavailability of kaempferol and improves therapeutic efficacy in dry eye disease

Dry eye disease (DED) is a common ocular surface disorder characterized by inflammation and oxidative stress. Kaempferol (KAE), a natural flavonoid, exhibits potent anti-inflammatory and antioxidant activities, but its physical and chemical properties limit its clinical application. This study aimed to develop a ion-sensitive in situ gel loaded with kaempferol niosomes (KAE-NIO-ISG) for enhanced DED therapy. KAE niosomes were prepared from tween 80, span 60, cholesterol and kaempferol by the thin-film hydration method and incorporated into an ion-sensitive in situ gel matrix. The prepared KAE-NIO-ISG system exhibited favorable nanoscale properties with particle size of 177.27 ± 1.26 nm. The formulation’s viscosity increased from 27.24 ± 0.49 cp to 238.71 ± 1.75 cp, after adding simulated tear fluid. The storage stability study demonstrated that the formulation possessed good stability and irritation test revealed that the formulation was well tolerated. Ocular pharmacokinetic study indicated that the formulation improved the drug’s bioavailability. Therapeutic efficacy was conducted using a benzalkonium chloride-induced dry eye mouse model and the results demonstrated that the efficacy of KAE exhibited in a dose-dependent manner and the efficacy of high-dose KAE was equivalent to cyclosporine. KAE-NIO-ISG is a promising therapeutic strategy for DED, offering good tolerability and improved bioavailability