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.
Lung-to-blood deliveryLow-hydrophilic liposomes crossed alveolar epithelial cells to deliver GLP-1 agonists systemically, achieving effective blood glucose control without injection
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
Who was studied
Mouse models (type 2 diabetes and OVA-induced allergic asthma)
What this study cannot 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.
How to read the evidence
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.
When this study was published
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.
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.
Questions still open
- 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?
Common questions
Could you eventually inhale semaglutide instead of injecting it?
Why is inhaled peptide delivery so difficult?
Read the original research
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
Citation
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