Pulmonary biodistribution and cellular uptake of intranasally administered monodisperse particles

Timothy M. Brenza, Latrisha K. Petersen, Yanjie Zhang, Lucas M. Huntimer, Amanda E. Ramer-Tait, Jesse M. Hostetter, Michael J. Wannemuehler, Balaji Narasimhan

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1368-1382
Number of pages15
JournalPharmaceutical Research
Volume32
Issue number4
DOIs
StatePublished - Apr 2015

Keywords

  • biodistribution
  • histology
  • nanoparticle
  • polyanhydrides
  • pulmonary
  • vaccines

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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  • Cite this

    Brenza, T. M., Petersen, L. K., Zhang, Y., Huntimer, L. M., Ramer-Tait, A. E., Hostetter, J. M., Wannemuehler, M. J., & Narasimhan, B. (2015). Pulmonary biodistribution and cellular uptake of intranasally administered monodisperse particles. Pharmaceutical Research, 32(4), 1368-1382. https://doi.org/10.1007/s11095-014-1540-y