Engineered Nanomicelles Delivering the Combination of Steroids and Antioxidants Can Mitigate Local and Systemic Inflammation, Including Sepsis.

Summary

Chimeric nanomicelles co-delivering dexamethasone and vitamin E accumulate at inflamed sites, reduce immune cell infiltration and proinflammatory cytokines, and prevent vascular injury. In both LPS endotoxemia and CLP sepsis models, they improved survival, supporting combined anti-inflammatory and antioxidant delivery to blunt hyperinflammation.

Key Findings

• DEX–VITE nanomicelles preferentially accumulated at inflamed sites via EPR effect and reduced acute inflammation in paw, lung, and liver models.
• In LPS-induced endotoxemia and CLP-induced sepsis, nanomicelles improved survival.
• Treatment reduced immune cell infiltration (neutrophils, macrophages), lowered proinflammatory cytokines, and prevented vascular damage.

Clinical Implications

If safety and pharmacokinetics are favorable, such combination nanotherapy could reduce steroid burden and adverse effects while controlling cytokine storm and vascular leakage in sepsis.

Limitations

• Preclinical stage without formal toxicity, biodistribution, and steroid-related adverse effect profiling
• Long-term outcomes and dosing strategies not defined

Future Directions

Conduct PK/toxicology studies, optimize dosing, and test efficacy with antibiotics/standard sepsis care in large-animal models before first-in-human trials.