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

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 ti...

Full description

Saved in:
Bibliographic Details
Published in:Biomaterials science 2022-12, Vol.1 (24), p.74-714
Main Authors: Allyn, Megan M, Rincon-Benavides, Maria A, Chandler, Heather L, Higuita-Castro, Natalia, Palmer, Andre F, Swindle-Reilly, Katelyn E
Format: Article
Language:English
Subjects:
Age related diseases
Atrophy
Catabolism
Cytotoxicity
Eye diseases
Macular degeneration
Nanoparticles
Oxidative stress
Proteins
Scavenging
Serum albumin
Sustained release
Toxicity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. ROS-responsive polydopamine nanoparticles sustain release of heme-albumin, increasing HO-1 expression in retinal cells, demonstrating a potential therapeutic approach for treatment of inflammatory conditions such as age-related macular degeneration.
ISSN:2047-4830
2047-4849
DOI:10.1039/d2bm00905f