Pulmonary Biodistribution and Cellular Uptake of Intranasally Administered Monodisperse Particles
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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.
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.
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.
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.
KEY WORDSpolyanhydrides nanoparticle biodistribution vaccines pulmonary histology
Antigen presenting cell
Hematoxylin and eosin
Mean fluorescence intensity
The authors wish to acknowledge funding from the ONR-MURI Award (NN00014-06-1-1176), the U.S. Army Medical Research and Materiel Command (Grant no. W81XWH-09-1-0386), and HRSA (Grant no. C76HF19578). The authors would also like to thank Shawn Rigby of the Iowa State Flow Cytometry Facility for his expertise in flow cytometry. BN acknowledges the Vlasta Klima Balloun Professorship in Chemical and Biological Engineering. The authors wish to thank Dr. Paola Boggiatto for useful discussions on the analysis of the flow cytometric data.
- 28.Roberts JR, Antonini JM, Porter DW, Chapman RS, Scabilloni JF, Young S-H, et al. Lung toxicity and biodistribution of Cd/Se-ZnS quantum dots with different surface functional groups after pulmonary exposure in rats. Part Fibre Toxicol. 2013;10(5).Google Scholar
- 40.Marsh LM, Cakarova L, Kwapiszewska G, von Wulffen W, Herold S, Seeger W, et al. Surface expression of CD74 by type II alveolar epithelial cells: a potential mechanism for macrophage migration inhibitory factor-induced epithelial repair. Am J Physiol Lung Cell Mol Physiol. 2009;296(3):L442–52.CrossRefPubMedGoogle Scholar
- 44.Geiser M, Kreyling WG. Deposition and biokinetics of inhaled nanoparticles. Part Fibre Toxicol. 2010;7(2).Google Scholar
- 59.Chavez-Santoscoy AV, Roychoudhury R, Pohl NLB, Wannemuehler MJ, Narasimhan B, Ramer-Tait AE. Tailoring the immune response by targeting C-type lectin receptors on alveolar macrophages using “pathogen-like” amphiphilic polyanhydride nanoparticles. Biomaterials. 2012;33:4762–72.CrossRefPubMedGoogle Scholar