Inhaled Nanoparticles Could Deliver Semaglutide and Liraglutide Through Your Lungs
By adjusting the surface properties of inhaled nanoparticles, researchers successfully delivered GLP-1 agonists like semaglutide through the lungs into the bloodstream, lowering blood sugar in diabetic mice without injections.
Quick Facts
What This Study Found
By tuning the surface hydrophilicity of inhaled liposome nanoparticles, researchers achieved two distinct delivery outcomes from the same lung-based platform. Low-hydrophilic liposomes loaded with GLP-1 receptor agonists (liraglutide or semaglutide) delivered the peptides systemically into the bloodstream, producing excellent blood sugar-lowering effects in diabetic mice. High-hydrophilic liposomes loaded with budesonide stayed in the lungs longer, treating asthma while reducing dosing frequency.
The mechanism: less hydrophilic particles crossed through alveolar epithelial cells more efficiently for systemic absorption, while more hydrophilic particles resisted both cellular transport and macrophage clearance, staying in the lungs longer.
Key Numbers
Liposomes with varying hydrophilicity levels tested · Liraglutide and semaglutide loaded · Type 2 diabetes mouse model · OVA-induced asthma mouse model · Reduced dosing frequency for budesonide
How They Did This
Researchers created a series of liposome nanoparticles with different surface hydrophilicity levels and loaded them with either GLP-1 agonists (liraglutide/semaglutide) or budesonide (an asthma drug). These were delivered by inhalation to mice in two disease models: type 2 diabetes and allergic asthma. Systemic absorption, pulmonary residence time, blood glucose levels, asthma symptom relief, and biocompatibility were all measured. Mechanistic studies examined transcellular transport through alveolar cells and macrophage clearance.
Why This Research Matters
GLP-1 drugs like semaglutide and liraglutide currently require injections, which remains a barrier for many patients. Inhaled delivery through the lungs could offer a needle-free alternative with rapid absorption. This study provides a design framework for creating inhaled GLP-1 formulations by controlling nanoparticle surface properties — a significant step toward making these peptide drugs more accessible.
The Bigger Picture
The race to develop non-injectable GLP-1 drugs is intense, with oral semaglutide already on the market. Inhaled delivery represents another frontier — the lungs have a massive surface area and thin epithelial barrier, making them ideal for rapid peptide absorption. This nanoparticle surface-tuning approach could accelerate the development of inhaled versions of semaglutide and other peptide drugs.
What This Study Doesn't Tell Us
This is an animal study in mice — lung anatomy and physiology differ between mice and humans, and inhaled delivery scaling to human lungs is a major challenge. Long-term safety of repeated liposome inhalation was not assessed. The specific doses and blood glucose reductions are not detailed in the abstract.
Questions This Raises
- ?Can this inhaled liposome technology scale to human lung delivery with sufficient bioavailability to match injectable GLP-1 doses?
- ?What are the long-term pulmonary safety implications of repeated nanoparticle inhalation?
- ?Could this approach be combined with dry powder inhaler technology for room-temperature-stable GLP-1 formulations?
Trust & Context
- Key Stat:
- Lung-to-blood delivery Low-hydrophilic liposomes crossed alveolar epithelial cells to deliver GLP-1 agonists systemically, achieving effective blood glucose control without injection
- Evidence Grade:
- This is a preclinical animal study demonstrating proof-of-concept for a drug delivery platform. While the results are promising, the technology has not been tested in humans and faces significant translational hurdles.
- Study Age:
- Published in 2025, this is a very recent study at the cutting edge of peptide drug delivery research, reflecting strong interest in non-injectable GLP-1 formulations.
- Original Title:
- Harnessing Surface Hydrophilicity of Inhalable Nanoparticles for Precision Delivery of Glucagon-like Peptide-1 Receptor Agonists or Anti-Asthmatic Therapeutics.
- Published In:
- ACS nano, 19(24), 22357-22375 (2025)
- Authors:
- Liu, Xi(2), Zhang, Lie, Li, Sa, Xing, Liyun, Ni, Mingjie, Huang, Minyi, Huang, Yuan
- Database ID:
- RPEP-12246
Evidence Hierarchy
Frequently Asked Questions
Could you eventually inhale semaglutide instead of injecting it?
This study provides early evidence that it's scientifically possible. The researchers successfully delivered semaglutide and liraglutide through the lungs of mice using specially designed nanoparticles. However, translating this to a human inhaler product would require years of further development and clinical trials.
Why is inhaled peptide delivery so difficult?
Peptides like semaglutide are large molecules that don't easily cross cell barriers. The lungs also have immune cells (macrophages) that clear foreign particles. This study solved both problems by tuning the nanoparticle surface to enhance transport through lung cells while avoiding immune clearance.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-12246APA
Liu, Xi; Zhang, Lie; Li, Sa; Xing, Liyun; Ni, Mingjie; Huang, Minyi; Huang, Yuan. (2025). Harnessing Surface Hydrophilicity of Inhalable Nanoparticles for Precision Delivery of Glucagon-like Peptide-1 Receptor Agonists or Anti-Asthmatic Therapeutics.. ACS nano, 19(24), 22357-22375. https://doi.org/10.1021/acsnano.5c05745
MLA
Liu, Xi, et al. "Harnessing Surface Hydrophilicity of Inhalable Nanoparticles for Precision Delivery of Glucagon-like Peptide-1 Receptor Agonists or Anti-Asthmatic Therapeutics.." ACS nano, 2025. https://doi.org/10.1021/acsnano.5c05745
RethinkPeptides
RethinkPeptides Research Database. "Harnessing Surface Hydrophilicity of Inhalable Nanoparticles..." RPEP-12246. Retrieved from https://rethinkpeptides.com/research/liu-2025-harnessing-surface-hydrophilicity-of
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.