Issue 24, 2022

Sustained release of heme–albumin as a potential novel therapeutic approach for age-related macular degeneration

Abstract

Globally, age-related macular degeneration (AMD) is the third most common visual impairment. Most often attributed to cellular fatigue with aging, over expression of reactive oxygen species (ROS) causes ROS accumulation in the retina, leading to chronic inflammatory immune signaling, cellular and tissue damage, and eventual blindness. If left uncontrolled, the disease will progress from the dry form of AMD to more severe forms such as geographic atrophy or wet AMD, hallmarked by choroidal neovascularization. There is no cure for AMD and treatment options are limited. Treatment options for wet AMD require invasive ocular injections or implants, yet fail to address the disease progressing factors. To provide more complete treatment of AMD, the application of a novel anti-inflammatory heme-bound human serum albumin (heme–albumin) protein complex delivered by antioxidant ROS scavenging polydopamine (PDA) nanoparticles (NPs) for sustained treatment of AMD was investigated. Through the induction of heme oxygenase-1 (HO-1) by heme–albumin in retinal pigment epithelial (RPE) cells, anti-inflammatory protection may be provided through the generation of carbon monoxide (CO) and biliverdin during heme catabolism. Our results show that the novel protein complex has negligible cytotoxicity towards RPE cells (ARPE-19), reduces oxidative stress in both inflammatory and ROS in vitro models, and induces a statistically significant increase in HO-1 protein expression. When incorporated into PDA NPs, heme–albumin was sustainably released for up to 6 months, showing faster release at higher oxidative stress levels. Through its ability to react with ROS, heme–albumin loaded PDA NPs showed further reduction of oxidative stress with minimal cytotoxicity. Altogether, we demonstrate that heme–albumin loaded PDA NPs reduce oxidative stress in vitro and can provide sustained therapeutic delivery for AMD treatment.

Graphical abstract: Sustained release of heme–albumin as a potential novel therapeutic approach for age-related macular degeneration

Supplementary files

Article information

Article type
Paper
Submitted
08 iyn 2022
Accepted
18 okt 2022
First published
02 noy 2022

Biomater. Sci., 2022,10, 7004-7014

Sustained release of heme–albumin as a potential novel therapeutic approach for age-related macular degeneration

M. M. Allyn, M. A. Rincon-Benavides, H. L. Chandler, N. Higuita-Castro, A. F. Palmer and K. E. Swindle-Reilly, Biomater. Sci., 2022, 10, 7004 DOI: 10.1039/D2BM00905F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements