The effect of particle size on the biodistribution of low-modulus hydrogel PRINT particles

J Control Release. 2012 Aug 20;162(1):37-44. doi: 10.1016/j.jconrel.2012.06.009. Epub 2012 Jun 15.

Abstract

There is a growing recognition that the deformability of particles used for drug delivery plays a significant role on their biodistribution and circulation profile. Understanding these effects would provide a crucial tool for the rational design of drug delivery systems. While particles resembling red blood cells (RBCs) in size, shape and deformability have extended circulation times and altered biodistribution profiles compared to rigid, but otherwise similar particles, the in vivo behavior of such highly deformable particles of varied size has not been explored. We report the fabrication of a series of discoid, monodisperse, low-modulus hydrogel particles with diameters ranging from 0.8 to 8.9 μm, spanning sizes smaller than and larger than RBCs. We injected these particles into healthy mice, and tracked their concentration in the blood and their distribution into major organs. These deformable particles all demonstrated some hold up in filtration tissues like the lungs and spleen, followed by release back into the circulation, characterized by decreases in particles in these tissues with concomitant increases in particle concentration in blood. Particles similar to red blood cells in size demonstrated longer circulation times, suggesting that this size and shape of deformable particle is uniquely suited to avoid clearance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acrylates / chemistry
  • Acrylates / pharmacokinetics
  • Animals
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacokinetics
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics*
  • Elastic Modulus
  • Erythrocytes / cytology
  • Female
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacokinetics*
  • Mice
  • Mice, Inbred BALB C
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics
  • Tissue Distribution

Substances

  • Acrylates
  • Drug Carriers
  • polyethylene glycol-dihydroxyl
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Polyethylene Glycols