Hexahistidine-metal assembly encapsulated fibroblast growth factor 21 for lipopolysaccharide-induced acute lung injury.
Summary
A pH-responsive hexahistidine-metal nano-assembly encapsulating FGF21 achieved high loading and stability and outperformed free FGF21 in LPS-induced ALI, decreasing edema (wet/dry ratio), BALF protein, and cell counts via both airway and intravenous delivery. This platform addresses key translational barriers for FGF21 in ARDS/ALI.
Key Findings
- HmA@FGF21 achieved >90% entrapment efficiency and >35% loading capacity with ~130 nm size, PDI ~0.28, and +24 mV zeta potential.
- In LPS-induced ALI, HmA@FGF21 reduced lung wet/dry ratio, BALF total protein, and total cell counts versus free FGF21.
- Therapeutic benefit was observed with both airway and intravenous administration routes.
Clinical Implications
Preclinical only; no immediate practice change. If safety and efficacy translate, targeted FGF21 delivery could become an adjunctive therapy for ALI/ARDS.
Why It Matters
Introduces a generalizable pulmonary delivery platform that enhances efficacy of a promising biologic (FGF21) across routes, potentially enabling translational advancement in ARDS therapeutics.
Limitations
- Preclinical LPS model only; lack of infection- or ventilation-related ARDS models.
- No data on pharmacokinetics, immunogenicity, or long-term safety.
Future Directions
Evaluate in infectious and ventilator-induced ARDS models, perform PK/toxicity studies, dose optimization, and assess scalability and manufacturability.
Study Information
- Study Type
- Case-control
- Research Domain
- Treatment
- Evidence Level
- V - Preclinical animal experiment comparing treated versus control groups; no human data.
- Study Design
- OTHER