TIPS pentacene loaded PEO-PDLLA core-shell nanoparticles have similar cellular uptake dynamics in M1 and M2 macrophages and in corresponding in vivo microenvironments

Nanomedicine. 2017 Apr;13(3):1255-1266. doi: 10.1016/j.nano.2016.12.015. Epub 2016 Dec 29.

Abstract

Nanoparticle based drug delivery platforms have the potential to transform disease treatment paradigms and therapeutic strategies, especially in the context of pulmonary medicine. Once administered, nanoparticles disperse throughout the lung and many are phagocytosed by macrophages. However, there is a paucity of knowledge regarding cellular up-take dynamics of nanoparticles due largely to macrophage heterogeneity. To address this issue, we sought to better define nanoparticle up-take using polarized M1 and M2 macrophages and novel TIPS-pentacene loaded PEO-PDLLA nanoparticles. Our data reveal that primary macrophages polarized to either M1 or M2 phenotypes have similar levels of nanoparticle phagocytosis. Similarly, M1 and M2 polarized macrophages isolated from the lungs of mice following either acute (Th1) or allergic (Th2) airway inflammation also demonstrated equivalent levels of nanoparticle up-take. Together, these studies provide critical benchmark information pertaining to cellular up-take dynamics and biodistribution of nanoparticles in the context of clinically relevant inflammatory microenvironments.

Keywords: Asthma; Inflammation; LPS; Nanoparticle; Pulmonary drug delivery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma
  • Cells, Cultured
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / metabolism*
  • Lung / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Organosilicon Compounds / administration & dosage*
  • Organosilicon Compounds / pharmacokinetics*
  • Polyesters / chemistry
  • Polyesters / metabolism*
  • Tissue Distribution

Substances

  • Drug Carriers
  • Epoxy Compounds
  • Organosilicon Compounds
  • PEO-poly(lactide)
  • Polyesters
  • bis(triisopropylsilylethynyl)pentacene