Advertisement

Utilizing the Lung as a Model to Study Nanoparticle-Based Drug Delivery Systems

  • Dylan K. McDaniel
  • Veronica M. Ringel-Scaia
  • Sheryl L. Coutermarsh-Ott
  • Irving C. AllenEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1831)

Abstract

Intranasal administration is a highly effective route for drug delivery and biodistribution studies. Indeed, this route of delivery has become the method of choice to distribute diverse pharmacological agents both locally and systemically. In the majority of preclinical animal models and in human patients, intranasal administration is the preferred method to deliver therapeutic agents to the airways and lungs. However, issues with drug stability and controlled release in the respiratory tract are common problems with many therapeutic agents. Nanoparticle delivery via intranasal administration has tremendous potential to circumvent these common issues. Over the past 30 years nanoparticles have gained increased interest as therapeutic delivery vehicles and as tools for improved bioimaging. Integral to the success of nanoparticles in drug delivery and biodistribution is the utilization of mouse models to characterize therapeutic strategies under physiologically relevant in situ conditions. Here, we describe a model of nanoparticle administration to the lungs utilizing intranasal administration and discuss a variety of highly useful techniques to evaluate nanoparticle up-take, biodistribution, and immune response. While these protocols have been optimized for intranasal administration of common fluorescently labeled nanoparticles, they can be applied to any nanoparticle or drug delivery system of interest targeting the lungs and airways.

Key words

Biodistribution Intranasal administration Inflammation Airway Flow cytometry 

Notes

Acknowledgments

Funding for this work was provided by the Virginia Tech Institute for Critical Technology and Applied Science and the Virginia Maryland College of Veterinary Medicine. Nanoparticles utilized in this protocol were provided by Prof. Richey M. Davis from the Virginia Tech Department of Chemical Engineering.

References

  1. 1.
    Djupesland PG (2013) Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res 3(1):42–62. https://doi.org/10.1007/s13346-012-0108-9CrossRefPubMedGoogle Scholar
  2. 2.
    Turker S, Onur E, Ozer Y (2004) Nasal route and drug delivery systems. Pharm World Sci 26(3):137–142CrossRefPubMedGoogle Scholar
  3. 3.
    Fortuna A, Alves G, Serralheiro A et al (2014) Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules. Eur J Pharm Biopharm 88(1):8–27. https://doi.org/10.1016/j.ejpb.2014.03.004CrossRefPubMedGoogle Scholar
  4. 4.
    Engelhardt L, Rohm M, Mavoungou C et al (2016) First steps to develop and validate a CFPD model in order to support the Design of Nose-to-Brain Delivered Biopharmaceuticals. Pharm Res. https://doi.org/10.1007/s11095-016-1875-7
  5. 5.
    Muralidharan P, Malapit M, Mallory E et al (2015) Inhalable nanoparticulate powders for respiratory delivery. Nanomedicine 11(5):1189–1199. https://doi.org/10.1016/j.nano.2015.01.007CrossRefPubMedGoogle Scholar
  6. 6.
    Grassin-Delyle S, Buenestado A, Naline E et al (2012) Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol Ther 134(3):366–379. https://doi.org/10.1016/j.pharmthera.2012.03.003CrossRefPubMedGoogle Scholar
  7. 7.
    Fromen CA, Rahhal TB, Robbins GR et al (2016) Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells. Nanomedicine 12(3):677–687. https://doi.org/10.1016/j.nano.2015.11.002CrossRefPubMedGoogle Scholar
  8. 8.
    Ramishetti S, Huang L (2012) Intelligent design of multifunctional lipid-coated nanoparticle platforms for cancer therapy. Ther Deliv 3(12):1429–1445. https://doi.org/10.4155/tde.12.127CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Suk JS, Kim AJ, Trehan K et al (2014) Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier. J Control Release 178:8–17. https://doi.org/10.1016/j.jconrel.2014.01.007CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Mastorakos P, da Silva AL, Chisholm J et al (2015) Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy. Proc Natl Acad Sci U S A 112(28):8720–8725. https://doi.org/10.1073/pnas.1502281112CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Roberts RA, Shen T, Allen IC et al (2013) Analysis of the murine immune response to pulmonary delivery of precisely fabricated nano- and microscale particles. PLoS One 8(4):e62115. https://doi.org/10.1371/journal.pone.0062115CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Dylan K. McDaniel
    • 1
  • Veronica M. Ringel-Scaia
    • 2
  • Sheryl L. Coutermarsh-Ott
    • 1
  • Irving C. Allen
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary MedicineVirginia TechBlacksburgUSA
  2. 2.Graduate Program in Translational Biology, Medicine, and HealthVirginia TechBlacksburgUSA
  3. 3.Department of Biomedical SciencesCarilion School of Medicine, Virginia TechRoanokeUSA

Personalised recommendations