Ophthalmic Drops with Nanoparticles Derived from a Natural Product for Treating Age-Related Macular Degeneration
- 15 December 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Applied Materials & Interfaces
- Vol. 12 (52), 57710-57720
- https://doi.org/10.1021/acsami.0c17296
Abstract
There is a continuing, urgent need for an ophthalmic (eye) drop for the clinical therapy of age-related macular degeneration (AMD), a leading cause of blindness. Here, we report the first formulation of an eye drop that is effective via autophagy for AMD treatment. This eye drop is based on a single natural product derivative (ACD), which is an amphiphilic molecule containing a 6-aminohexanoate group (H2N(CH2)5COO−). We demonstrate that this eye drop reverses the abnormal angiogenesis induced in a primate model of AMD that has the pathological characteristics close to that of human AMD. The ACD molecule was self-assembled in an aqueous environment leading to nanoparticles (NPs) about 9.0 nm in diameter. These NPs were encapsulated in calcium alginate hydrogel. The resulting eye drop effectively slowed the release of ACD and displayed extended release periods in both simulated blood (pH 7.4) and inflammatory (pH 5.2) environments. We show that the eye drop penetrated both the corneal and blood–eye barriers and reached the fundus. With low cellular toxicity, the drop targeted S1,25D3-membrane-associated rapid response steroid-binding protein (1,25D3-MARRS) promoting autophagy in a dose-dependent manner. In addition, the drop inhibited cell migration and tubular formation. On the other hand, when protein 1,25D3-MARRS was knocked down, the eye drop did not exhibit such inhibition functionalities. Our study indicates that the 6-aminohexanoate group on self-assembled NPs encapsulated in hydrogel leads to the positive in vivo outcomes. The present formulation offers a promising approach for clinical treatment of human AMD.Keywords
Funding Information
- Sichuan University (2019JCXK3245)
- Ministry of Science and Technology of the People's Republic of China (2019ZX09201005-005-001, 2019ZX09201005-005-002, 2019ZX09201005-005-004)
- China Postdoctoral Science Foundation (2018M640932, 2019T120854)
- Department of Science and Technology of Sichuan Province (2019YJ0095, 2020YFS0554)
- National Natural Science Foundation of China (81673710, 81803866, 81973580)
- West China Hospital, Sichuan University (2018HXBH061, 2019HXBH024)
- West China Innovative Chinese Medicine and Health Products Research Academician Workstation of Academician Zhang Boli and Academician Zhu Beiwei, West China Hospital, Sichuan University (HXYS19001, HXYS19002)
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