Niosomal In Situ Gel Enhances the Ocular Bioavailability of Kaempferol and Improves Therapeutic Efficacy in Dry Eye Disease

Background Conventional dry eye formulations frequently demonstrate low bioavailability and necessitate high dosing frequency, resulting in poor patient compliance. This is largely due to the ocular physiological barrier. Aim of the study We developed a novel ophthalmic formulation, kaempferol-loaded niosomal in situ gel (KAE-NIO-ISG), to improve the treatment of dry eye disease by increasing the ocular bioavailability and therapeutic efficacy. Materials and methods KAE-NIO-ISG was prepared by thin-film hydration and incorporated into an ion-sensitive in situ gel. Results The optimized KAE-NIO-ISG exhibited nanoscale characteristics particle size (PS) 177.27± 1.26 nm; polydispersity index (PDI) 0.21±0.03. The viscosity increased markedly upon dilution with simulated tear fluid (from 27.24±0.49 cP to 238.71±1.75 cP), indicating effective in situ gelation. Approximately 60% of the kaempferol（KAE） was released after 72 h, which is substantially greater than that of the KAE suspension (16.62±5.74%). The formulation demonstrated robust storage stability, no cytotoxicity in Human corneal epithelial cells (HCE-2) or Rat conjunctival epithelial cells (rPCEC), and excellent ocular tolerance. Pharmacokinetic analysis revealed that compared with the KAE suspension, KAE-NIO-ISG increased AUC _{0-180 min} values in the rabbit cornea and conjunctiva by 23.52-fold and 3.98-fold, respectively. In vivo pharmacodynamics revealed dose-dependent efficacy, with the high-dose group achieving effects comparable to those of cyclosporine A (CsA). Conclusions In summary, KAE-NIO-ISG is a well-tolerated, efficient therapeutic approach for dry eye disease that significantly enhances ocular bioavailability and therapeutic outcomes.