Self-assembled rapamycin prodrug nanoparticles for posterior segment targeting and effective treatment of experimental uveitis

The treatment of posterior uveitis remains challenging due to the need for long-term medication and the limited efficacy of current therapies. In this study, we developed an injectable rapamycin-based nanoparticle formulation designed to extend intraocular residence time and enhance retinal penetration, thereby improving therapeutic outcomes. The nanoparticles were formed via self-assembly of rapamycin conjugated with a hydrophobic alkyl chain, yielding uniformly spherical particles with an average diameter of approximately 90 nm. In vitro experiments confirmed that the formulation exhibited minimal cytotoxicity, potent anti-inflammatory effects, inhibition of endothelial cell migration, and efficient uptake by retinal pigment epithelial (RPE) cells. In vivo imaging demonstrated that the nanoparticles rapidly localized to the RPE layer of the posterior segment following intravitreal injection, in contrast to the free drug. Moreover, experimental autoimmune uveoretinitis (EAU) rats treated with nanoparticles exhibited a substantial alleviation of ocular inflammation and a concomitant reduction in the expression of inflammatory markers, including CD45, CD68, IBA-1, and IL-17.