Ultra-small-size Astragaloside-IV loaded lipid nanocapsules eye drops for the effective management of dry age-related macular degeneration

Background Age-related macular degeneration (AMD) is a major cause of severe visual loss in elderly people. The treatments for dry AMD (dAMD) are severely limited so far. In this work, we aim to develop an eye drop to protect retinal functions against oxidative stress and apoptosis for improving dAMD management. Methods Astragaloside-IV (ASIV) was prepared into phospholipid complex and loaded into three sizes (20, 50 and 90 nm) of ASIV lipid nanocapsules (ASIV-LNCs). The penetration and distribution of LNCs were investigated. DAMD mice model was induced by NaIO₃, and therapeutic effect was evaluated by electroretinography (ERG), histological examination, apoptosis and ROS detection. Results The ocular penetration and pharmacokinetic studies corroborated the feasibility of the LNCs to reach the fundus, and ultra-small-size LNCs (ASIV-LNCs-20) had the best delivery effect. ASIV-LNCs-20 was able to decrease ROS production and reduce the apoptosis rate from 5.12% to 0.533%. ERG and H&E staining results confirmed ASIV-LNCs-20 had a good protective effect on the morphology and function of the retina. Conclusions These results suggest that ASIV-LNCs can be a promising therapy approach for dAMD, and this research also offers new possibilities for further applications of LNCs as a drug delivery system for other eye diseases. Abbreviations AMD: Age-related macular degeneration;AREDS Age-related eye disease study; ASIV: Astragaloside-IV;AUC: Area under the concentration-time curve; dAMD: Dry age-related macular degeneration; DHE: Dihydroethidium; DL: Drug Loading; DLS: Dynamic light scattering; DSC: Differential scanning calorimetry; EE: Entrapment efficiency; ELSD: Evaporative light scattering detector; ERG: Electroretinographic; H&E: Hematoxylin and Eosin; I.S.: Internal standard; LB: Langmuir-Blodgett; LNCs: Lipid nanocapsules; MCT: Medium-chain triacylglycerol; ONL: Outer nuclear layer; OPL: Outer plexiform layer; PDI: Polydispersity index; PR: Photoreceptor;ROS: Reactive oxygen species; RPE: Retinal pigment epithelium; TEM: Transmission electron microscope; wAMD: Wet age-related macular degeneration.

Keywords: Dry age-related macular degeneration; astragaloside-IV; eye drops; lipid nanocapsules; ultra-small size.