Aortic plaque-targeted andrographolide delivery with oxidation-sensitive micelle effectively treats atherosclerosis via simultaneous ROS capture and anti-inflammation

Nanomedicine. 2018 Oct;14(7):2215-2226. doi: 10.1016/j.nano.2018.06.010. Epub 2018 Jun 30.

Abstract

Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Andrographolide-loaded micelle was assembled from the block copolymer of poly(ethylene glycol) and poly(propylene sulphide) (PEG-PPS) for the purpose of simultaneously decreasing inflammatory response and the level of reactive oxygen species (ROS) to treat atherosclerosis. Owing to the ROS-responsive nature of PEG-PPS, the micelle not only serves as a stimuli-responsive drug carrier to quickly release the encapsulated drug, andrographolide, but also consumes ROS by itself at the pathologic sites, upon which the expressions of pro-inflammatory cytokines are effectively suppressed and oxidative stress is alleviated. Consequently, the andrographolide-loaded micelle demonstrated remarkable therapeutic effects both in vitro and in vivo. In conclusion, the andrographolide-loaded PEG-PPS micelle can synchronically alleviate inflammation and oxidative stress, providing a promising and innovative strategy against atherosclerosis.

Keywords: Andrographolide; Atherosclerosis; Inflammation; Oxidative stress; ROS-responsive polymers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / pathology
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Diterpenes / administration & dosage
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Female
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Mice, Knockout, ApoE
  • Micelles
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Plaque, Atherosclerotic / drug therapy*
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Polyethylene Glycols / chemistry
  • Polymers / administration & dosage
  • Polymers / chemistry
  • Reactive Oxygen Species / metabolism*

Substances

  • Diterpenes
  • Drug Carriers
  • Micelles
  • Polymers
  • Reactive Oxygen Species
  • Polyethylene Glycols
  • andrographolide