Shape induced inhibition of phagocytosis of polymer particles - PubMed (original) (raw)

Shape induced inhibition of phagocytosis of polymer particles

Julie A Champion et al. Pharm Res. 2009 Jan.

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.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

A schematic diagram illustrating how local shape is defined. T̄ represents the average of tangential angles near the point of cell contact. Ω is the angle between T̄ and the membrane normal at the site of attachment, N̄. A _Ω_=2.5° for cell attachment at end of worm. B _Ω_=87.5° for cell attachment on side of worm.

Fig. 2

Fig. 2

Scanning electron micrographs of polystyrene A worms stretched from 3 μm spheres and B worms stretched from 1 μm spheres. Scale bars = 10 μm (A) and 2 μm (B).

Fig. 3

Fig. 3

Time-lapse video microscopy clips at 0, 1, 2, 3, 4 and 32 min after attachment of IgG-adsorbed PS particles to alveolar macrophages. A Macrophage internalizes 3 μm sphere quickly following attachment. B Macrophage attaches to side of worm, but does not internalize it. Images have been cropped and magnified identically to show cell/particle detail. Scale bars = 5 μm.

Fig. 4

Fig. 4

Average number of spherical and worm-like IgG-adsorbed particles internalized in 22 h as determined by fluorescence microscopy. Patterned bars indicate particle volumes equivalent to 3 μm spheres (p<0.0000031) and solid bars indicate particle volumes equivalent to 1 μm spheres (p<0.000024). At least 50 cells were counted for each sample.

Fig. 5

Fig. 5

Colored scanning electron micrographs demonstrate the flexibility of IgG-adsorbed (A–C 1μm volume; D 3 μm volume) worm-like particles and ability of macrophages to bend worms by attachment at different points. Scale bars = 2 μm.

Fig. 6

Fig. 6

Colored scanning electron micrograph shows macrophage internalizing an IgG-adsorbed worm (3 μm volume) and the effect of internalization on cell shape. Scale bar = 5 μm.

Similar articles

Cited by

References

    1. Langer R. New methods of drug delivery. Science. 1990;249:1527–1533. - PubMed
    1. Koval M, Preiter K, Adles C, Stahl PD, Steinberg TH. Size of IgG-opsonized particles determines macrophage response during internalization. Exp Cell Res. 1998;242:265–273. - PubMed
    1. Xiang SD, Scholzen A, Minigo G, David C, Apostolopoulos V, Mottram PL, Plebanski M. Pathogen recognition and development of particulate vaccines: Does size matter. Methods. 2006;40:1–9. - PubMed
    1. Illum L, Davis SS, Wilson CG, Thomas NW, Frier M, Hardy JG. Blood clearance and organ deposition of intravenously administered colloidal particles—the effects of particle size, nature and shape. Int J Pharm. 1982;12:135–146.
    1. Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: Theory to practice. Pharm Rev. 2001;53:283–318. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources