Shape Induced Inhibition of Phagocytosis of Polymer Particles

Pharm Res. 2009 Jan;26(1):244-9. doi: 10.1007/s11095-008-9626-z. Epub 2008 Jun 12.

Abstract

Purpose: To determine if particle shape can be engineered to inhibit phagocytosis of drug delivery particles by macrophages, which can be a significant barrier to successful therapeutic delivery.

Methods: Non-spherical polystyrene particles were fabricated by stretching spherical particles embedded in a polymer film. A rat alveolar macrophage cell line was used as model macrophages. Phagocytosis of particles was assessed using time-lapse video microscopy and fluorescence microscopy.

Results: We fabricated worm-like particles with very high aspect ratios (>20). This shape exhibits negligible phagocytosis compared to conventional spherical particles of equal volume. Reduced phagocytosis is a result of decreasing high curvature regions of the particle to two single points, the ends of the worm-like particles. Internalization is possible only at these points, while attachment anywhere along the length of the particles inhibits internalization due to the low curvature.

Conclusions: Shape-induced inhibition of phagocytosis of drug delivery particles is possible by minimizing the size-normalized curvature of particles. We have created a high aspect ratio shape that exhibits negligible uptake by macrophages.

Publication types

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

MeSH terms

  • Animals
  • Catalase / administration & dosage*
  • Catalase / chemistry*
  • Catalase / pharmacokinetics
  • Chemistry, Pharmaceutical
  • Drug Carriers*
  • Drug Compounding
  • Emulsions
  • Excipients
  • Freezing
  • Hydrogen Peroxide / chemistry
  • Indicators and Reagents
  • Mice
  • Microscopy, Electron, Scanning
  • Nanoparticles / chemistry*
  • Nanotubes / chemistry*
  • Particle Size
  • Peptide Hydrolases / chemistry
  • Polyethylene Glycols / chemistry*
  • Tissue Distribution

Substances

  • Drug Carriers
  • Emulsions
  • Excipients
  • Indicators and Reagents
  • Polyethylene Glycols
  • Hydrogen Peroxide
  • Catalase
  • Peptide Hydrolases