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

ABSTRACT

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

Graphical abstract

KEYWORDS:

• Dry age-related macular degeneration
• astragaloside-IV
• lipid nanocapsules
• eye drops
• ultra-small size

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was supported by the National Mega-project for Innovative Drugs [2019ZX09721001], Major Project of National Science and Technology ‘Creation of Major New Drugs’ from China [2018ZX09721002-002], China Postdoctoral Science Foundation Grant [2019M651149], Liaoning Revitalization Talents Program [XLYC1907111, XLYC1908031], Liaoning Province Doctoral Start-up Fund Program [2019-BS-226], Liaoning Province Natural Science Fund Project [20180551031], Overseas Returnees Start-up Fund from Shenyang Pharmaceutical University [GGJJ2018102].