Nanoparticle diffusion in respiratory mucus from humans without lung disease

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Respiratory Physiology

Background:

• Respiratory mucus acts as a critical defense mechanism, trapping inhaled particles like pathogens and pollutants.
• Understanding particle transport within respiratory mucus is crucial for assessing health risks and developing targeted therapies.
• Current knowledge gaps exist regarding the influence of particle size and surface chemistry on mucus mobility in healthy human airways.

Purpose of the Study:

• To investigate the effect of particle size and polyethylene glycol (PEG) coating on nanoparticle transport within human respiratory mucus.
• To determine the muco-penetration capabilities of engineered nanoparticles in healthy respiratory mucus.
• To establish design criteria for therapeutic nanoparticles aimed at breaching the respiratory mucus barrier.

Main Methods:

• Collected human respiratory mucus from surgical patients without respiratory comorbidities.
• Prepared polymeric nanoparticles with and without dense low molecular weight polyethylene glycol (PEG) coatings.
• Compared the transport rates of 100 nm, 200 nm, and ≥500 nm PEG-coated nanoparticles versus uncoated nanoparticles within the mucus.
• Utilized bulk rheometry to characterize the macroscopic viscoelastic properties of the respiratory mucus.

Main Results:

• PEG-coated nanoparticles of 100 nm and 200 nm diameters exhibited rapid mucus penetration, with speeds 15- and 35-fold higher than uncoated particles, respectively.
• PEG-coated nanoparticles ≥500 nm in diameter were immobilized by the mucus mesh, indicating steric hindrance.
• Despite mucus's macroscopic viscoelasticity, small, muco-inert nanoparticles behaved as if penetrating a viscous liquid.

Conclusions:

• Nanoparticle size and surface chemistry (muco-inertness) are critical determinants of penetration through respiratory mucus.
• Small (100-200 nm) PEG-coated nanoparticles can effectively overcome the respiratory mucus barrier.
• These findings provide essential design principles for developing advanced nanoparticle-based drug delivery systems targeting the airway epithelium.