Inflammation-Responsive Drug-Conjugated Dextran Nanoparticles Enhance Anti-Inflammatory Drug Efficacy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Stimuli-responsive nanoparticles (NPs) offer enhanced drug delivery specificity for biomedical applications.
• Targeting inflammatory diseases requires precise drug release mechanisms.
• Reactive oxygen species (ROS) and low pH are characteristic of inflammatory environments.

Purpose of the Study:

• To design a stable, inflammation-specific drug release system.
• To create dual-responsive nanoparticles (NPs) utilizing ROS and pH triggers.
• To develop a dextran-drug conjugate for targeted delivery of naproxen.

Main Methods:

• Synthesized a reactive oxygen species (ROS)-responsive dextran-drug conjugate (Nap-Dex) using naproxen and phenylboronic acid (PBA).
• Formulated dual-responsive NPs by blending Nap-Dex with acid-sensitive acetalated dextran.
• Evaluated drug release kinetics and anti-inflammatory efficacy in lipopolysaccharide (LPS)-activated macrophages.

Main Results:

• Naproxen conjugation reached up to 87% functionalization on dextran units.
• Complete drug release was achieved within 20 minutes at 10 mM H2O2.
• Dual-responsive NPs demonstrated significantly higher reduction of proinflammatory cytokines (IL-6 and TNFα) compared to free naproxen.
• ROS-scavenging effects contributed to the enhanced anti-inflammatory activity.

Conclusions:

• Functionalized carbohydrate polymer-drug conjugates, particularly using PBA, offer a promising strategy for enhanced drug efficacy.
• The developed dual-responsive NPs show high specificity for inflammatory environments, improving therapeutic outcomes.
• This approach holds potential for various drug delivery applications in inflammatory diseases.