Shape induced inhibition of phagocytosis of polymer particles.
OBJECTIVE
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.
Department of Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA. jchampio@caltech.edu
Julie A
JA
Champion
Samir
S
Mitragotri
D000818:Animals; D002374:Catalase / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D005079:Excipients; D005615:Freezing; D006861:Hydrogen Peroxide / Q000737:chemistry; D007202:Indicators and Reagents; D051379:Mice; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D043942:Nanotubes / Q000737:chemistry*; D010316:Particle Size; D010447:Peptide Hydrolases / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution
D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D007202:Indicators and Reagents; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase; D010447:Peptide Hydrolases