The impact of size and charge on the pulmonary pharmacokinetics and immunological response of the lungs to PLGA nanoparticles after intratracheal administration to rats

• Published in: Nanomedicine Vol. 30; p. 102291
• Main Authors: Haque, Shadabul, Pouton, Colin W., McIntosh, Michelle P., Ascher, David B, Keizer, David W, Whittaker, Michael R., Kaminskas, Lisa M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2020
• Subjects: Clearance; Lungs; Nanoparticles; Pharmacokinetics; PLGA; Nanoparticles; PLGA; Clearance; Lungs; Pharmacokinetics
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2020.102291

Polylactide-co-glycolide (PLGA) nanoparticles are one of the most commonly explored biodegradable polymeric drug carriers for inhaled delivery. Despite their advantages as inhalable nanomedicine scaffolds, we still lack a complete understanding of the kinetics and major pathways by which these materials are cleared from the lungs. This information is important to evaluate their safety over prolonged use and enable successful clinical translation. This study aimed to determine how the size and charge of 3H-labeled PLGA nanoparticles affect the kinetics and mechanisms by which they are cleared from the lungs and their safety in the lungs. The results showed that lung clearance kinetics and retention patterns were more significantly defined by particle size, whereas lung clearance pathways were largely influenced by particle charge. Each of the nanoparticles caused transient inflammatory changes in the lungs after a single dose that reflected lung retention times.
The particle size and charge significantly impact the clearance kinetics and lung clearance mechanisms of inhaled PLGA nanoparticles. The surface charge influences the lung clearance pathways whereas particle size defines the lung retention patterns and clearance kinetics of PLGA nanoparticles. PLGA nanoparticle caused transient but reversible inflammatory changes in the lungs after a single dose that reflected lung retention times. [Display omitted]