Enhanced ocular delivery of rapamycin prodrug for the treatment of corneal alkali burns

Corneal alkali burns often result in blindness due to impaired healing processes. The primary contributing factors include inflammatory reactions, corneal neovascularization, and corneal stromal fibrosis following injury. Currently, glucocorticoids are widely employed to alleviate symptoms associated with corneal alkali burns. However, their use is limited to 1–2 weeks post-injury due to the risk of inducing corneal melting, which poses a significant safety concern. Rapamycin, a well-established immunosuppressive agent, exhibits anti-angiogenic and anti-fibrotic properties beneficial for corneal health. Nevertheless, its poor water solubility and ocular barriers limit its bioavailability, as only a minimal amount of the drug can penetrate the eye. To address these limitations, we developed a delivery system utilizing Sodium taurocholate (NaTC) to encapsulate rapamycin prodrugs, thereby enhancing their water solubility and ocular permeability, and consequently improved bioavailability. Our findings demonstrate that this delivery system significantly enhanced rapamycin’s solubility and effectively mitigated post-injury inflammatory responses, corneal neovascularization, and corneal stromal fibrosis. Compared with glucocorticoids, this system offered superior therapeutic efficacy and a longer duration of action. These results provide promising alternatives for treating corneal alkali burns and may also be applicable to other anterior segment diseases.