Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles

Timothy J. Merkel, Stephen W. Jones, Kevin P. Herlihy, Farrell R. Kersey, Adam R. Shields, Mary Napier, J. Christopher Luft, Huali Wu, William C. Zamboni, Andrew Z. Wang, James E. Bear, Joseph M. DeSimone

Research output: Contribution to journalArticlepeer-review

420 Scopus citations

Abstract

It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.

Original languageEnglish (US)
Pages (from-to)586-591
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number2
DOIs
StatePublished - Jan 11 2011
Externally publishedYes

Keywords

  • Biomimetic
  • Deformability
  • Drug carriers
  • Long circulating
  • Red blood cell mimic

ASJC Scopus subject areas

  • General

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