Inhibition of Corneal Neovascularization and Pharmacokinetic Study of Cyclodextrin Inclusion of Oroxin B Eye Drops

The aim of this study was to develop an eye drop formulation of Oroxin B, assess its stability and local tolerability, and evaluate its therapeutic efficacy against corneal neovascularization (CNV) along with its ocular pharmacokinetic profile.

The anti-angiogenic activity of Oroxin B was assessed in VEGF-induced human umbilical vein endothelial cells (HUVECs). Oroxin B eye drops (0.2%, 0.5%, 1.0% w/v) were prepared using hydroxypropyl-β-cyclodextrin (HP-β-CD). Their stability was tested under stress and long-term conditions, and ocular tolerance was evaluated in a 21-day rabbit study (1.0% drops). Efficacy was then tested in an alkali-burn rat CNV model. Ocular pharmacokinetics and metabolites were analyzed in rabbits using UPLC-MS/MS.

Oroxin B demonstrated dose-dependent anti-angiogenic effects in VEGF-induced HUVECs. A corresponding 25% HP-β-CD eye drop formulation was developed and shown to be stable under stress testing. All concentrations remained stable for 3 months at 25°C, though the 1.0% formulation precipitated at 2-8°C. In rabbits, the drops were well-tolerated, causing no ocular irritation or damage. In an alkali-burn rat model, they significantly reduced CNV and inflammation. Pharmacokinetic studies confirmed rapid corneal absorption, high local exposure, partial metabolism to baicalein, and negligible systemic absorption.

Oroxin B shows potent anti-angiogenic properties. The developed cyclodextrin-based eye drops are stable at room temperature and well-tolerated. They effectively reduced CNV through targeted corneal delivery of the active parent compound and its local bioactive metabolite, with minimal systemic exposure. These findings establish Oroxin B as a viable candidate for anti-angiogenic therapy.