Orally deliverable sequence-targeted astaxanthin nanoparticles for colitis alleviation.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacology

Background:

• Ulcerative colitis (UC) poses significant healthcare costs and requires efficient interventions.
• Orally targeted anti-inflammatory agents are crucial for effective UC management.
• Astaxanthin shows potential therapeutic benefits but requires optimized delivery.

Purpose of the Study:

• To develop sequence-targeted astaxanthin nanoparticles for enhanced UC treatment.
• To evaluate the targeting efficiency, drug release, and anti-inflammatory effects of the nanoparticles in vivo.
• To investigate the impact of the nanoparticles on gut microbiota and short-chain fatty acid production.

Main Methods:

• Astaxanthin nanoparticles were synthesized using whey protein isolate-dextran conjugates and coated with lipoic acid-hyaluronic acid.
• Macrophage and mitochondria targeting abilities were assessed using Pearson's correlation coefficient.
• In vivo imaging tracked nanoparticle accumulation in the colon of UC mice.
• In vitro studies evaluated reduction-stimulus release in the presence of glutathione (GSH).
• In vivo experiments assessed anti-inflammatory effects via the TLR4/MyD88/NF-κB pathway and analyzed gut microbiota composition.

Main Results:

• The nanoparticles demonstrated excellent targeting to macrophages (PCC=0.84) and mitochondria (PCC=0.92).
• Significant accumulation of nanoparticles was observed in the colon tissues of UC mice.
• Astaxanthin release was triggered by reduction stimulus (10 mM GSH at pH 7.4).
• The nanoparticles effectively alleviated inflammation by modulating the TLR4/MyD88/NF-κB signaling pathway.
• UC mice treated with nanoparticles showed improved gut microbiota composition and short-chain fatty acid production.

Conclusions:

• Sequence-targeted astaxanthin nanoparticles exhibit excellent targeting and reduction-responsive release properties.
• These nanoparticles effectively alleviate UC inflammation and positively modulate gut microbiota.
• This novel nanoparticle system represents a promising strategy for ulcerative colitis therapy.