Shape Induced Inhibition of Phagocytosis of Polymer Particles (original) (raw)

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.

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Acknowledgements

Authors acknowledge Alejandro Sanchez, Santosh Gupta, and Poornima Kolhar for assistance. JAC acknowledges a graduate fellowship from the National Science Foundation. This research was supported by the Program of Excellence in Nanotechnology by the National Institutes of Health.

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Author notes

1. Julie A. Champion
   Present address: Department of Chemical Engineering, California Institute of Technology, Pasadena, California, 91125, USA

Authors and Affiliations

1. Department of Chemical Engineering, University of California, Santa Barbara, California, 93106, USA
   Samir Mitragotri

Authors

1. Julie A. Champion
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2. Samir Mitragotri
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Corresponding author

Correspondence toSamir Mitragotri.

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Champion, J.A., Mitragotri, S. Shape Induced Inhibition of Phagocytosis of Polymer Particles.Pharm Res 26, 244–249 (2009). https://doi.org/10.1007/s11095-008-9626-z

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• Received: 10 March 2008
• Accepted: 05 May 2008
• Published: 12 June 2008
• Issue Date: January 2009
• DOI: https://doi.org/10.1007/s11095-008-9626-z

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