Pulmonary Biodistribution and Cellular Uptake of Intranasally Administered Monodisperse Particles

• Published in: Pharmaceutical research Vol. 32; no. 4; pp. 1368 - 1382
• Main Authors: Brenza, Timothy M., Petersen, Latrisha K., Zhang, Yanjie, Huntimer, Lucas M., Ramer-Tait, Amanda E., Hostetter, Jesse M., Wannemuehler, Michael J., Narasimhan, Balaji
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.04.2015; Springer Nature B.V
• Subjects: Administration, Intranasal; Anhydrides - chemical synthesis; Anhydrides - chemistry; Anhydrides - pharmacokinetics; Animals; Biochemistry; Biocompatible Materials - chemical synthesis; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacokinetics; Biodegradable materials; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Decanoic Acids - chemical synthesis; Decanoic Acids - chemistry; Decanoic Acids - pharmacokinetics; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug delivery systems; Female; Histology; Lung - immunology; Lung - metabolism; Medical Law; Mice, Inbred C57BL; Nanoparticles; Particle Size; Phagocytes - immunology; Phagocytes - metabolism; Phagocytosis; Pharmacology; Pharmacology/Toxicology; Pharmacy; Research Paper; Surface Properties; Tissue Distribution; Vaccines; Vaccines - administration & dosage; nanoparticle; pulmonary; biodistribution; histology; vaccines; polyanhydrides
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-014-1540-y

Purpose For the rational design of nanovaccines against respiratory pathogens, careful selection of optimal particle size and chemistry is paramount. This work investigates the impact of these properties on the deposition, biodistribution, and cellular interactions of nanoparticles within the lungs. Method In this work, biodegradable poly(sebacic anhydride) (poly(SA)) nanoparticles of multiple sizes were synthesized with narrow particle size distributions. The lung deposition and retention as well as the internalization by phagocytic cells of these particles were compared to that of non-degradable monodisperse polystyrene nanoparticles of similar sizes. Results The initial deposition of intranasally administered particles in the lungs was dependent on primary particle size, with maximal deposition occurring for the 360–470 nm particles, regardless of chemistry. Over time, both particle size and chemistry affected the frequency of particle-positive cells and the specific cell types taking up particles. The biodegradable poly(SA) particles associated more closely with phagocytic cells and the dynamics of this association impacted the clearance of these particles from the lung. Conclusions The findings reported herein indicate that both size and chemistry control the fate of intranasally administered particles and that the dynamics of particle association with phagocytic cells in the lungs provide important insights for the rational design of pulmonary vaccine delivery vehicles.