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Edaravone-loaded ROS-responsive nanosystem for targeted ischemic stroke therapy by crossing the gut-brain barrier.

Wujing Cao¹, Xinxin Liu², Wensheng Wang¹

¹College of Life Sciences, Henan Normal University, Xinxiang, 453007, China.

Materials Today. Bio

|June 29, 2026

Summary

A novel nanoplatform enhances oral ischemic stroke therapy by improving drug absorption and brain delivery. This engineered system targets specific transporters and responds to oxidative stress for effective neuroprotection.

Keywords:

Equilibrative nucleoside transporters Gut–brain barrier Ischemic stroke Lipoic acid ROS-responsive

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Published on: January 18, 2016

Area of Science:

Nanotechnology
Neuroscience
Pharmacology

Background:

Oral drug delivery for ischemic stroke is limited by poor absorption, blood-brain barrier (BBB) penetration, and insufficient brain retention.
Developing effective oral therapies requires overcoming these barriers to achieve sustained therapeutic levels in the brain.

Purpose of the Study:

To engineer a dual-targeting, size-transformable nanoplatform for enhanced oral delivery of neuroprotectants for ischemic stroke treatment.
To overcome limitations in intestinal absorption, BBB penetration, and brain retention of therapeutic agents.

Main Methods:

Development of a nanoplatform (LAG-PA/PMP NPs) from lipoic acid-guanine (LAG) and phenylboronic acid (PA), encapsulating edaravone (PMP).
Utilizing guanine for targeting equilibrative nucleoside transporter 2 (ENT2) and exploiting ROS-responsive cleavage for controlled release and size transformation.
Evaluating oral bioavailability, toxicity, and therapeutic efficacy in MCAO rat models of ischemic stroke.

Main Results:

The nanoplatform demonstrated high oral bioavailability (86.1%) with no significant toxicity.
LAG-PA/PMP NPs successfully crossed the intestinal barrier and BBB, facilitated by ENT2 targeting.
The system showed enhanced brain retention and controlled PMP release triggered by ROS, leading to reduced cerebral infarction, inflammation, and oxidative stress in MCAO rats.

Conclusions:

The engineered dual-targeting, morphology-adaptable nanoplatform offers a promising strategy for highly efficient oral ischemic stroke therapy.
This approach significantly improves neuroprotection compared to free drug administration.
The nanoplatform overcomes key challenges in oral drug delivery for neurological disorders.