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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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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DOI: https://doi.org/10.1007/s11095-008-9626-z