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Polymer Chemistry Influences Monocytic Uptake of Polyanhydride Nanospheres

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Abstract

Purpose

To demonstrate that polyanhydride copolymer chemistry affects the uptake and intracellular compartmentalization of nanospheres by THP-1 human monocytic cells.

Methods

Polyanhydride nanospheres were prepared by an anti-solvent nanoprecipitation technique. Morphology and particle diameter were confirmed via scanning election microscopy and quasi-elastic light scattering, respectively. The effects of varying polymer chemistry on nanosphere and fluorescently labeled protein uptake by THP-1 cells were monitored by laser scanning confocal microscopy.

Results

Polyanhydride nanoparticles composed of poly(sebacic anhydride) (SA), and 20:80 and 50:50 copolymers of 1,6-bis-(p-carboxyphenoxy)hexane (CPH) anhydride and SA were fabricated with similar spherical morphology and particle diameter (200 to 800 nm). Exposure of the nanospheres to THP-1 monocytes showed that poly(SA) and 20:80 CPH:SA nanospheres were readily internalized whereas 50:50 CPH:SA nanospheres had limited uptake. The chemistries also differentially enhanced the uptake of a red fluorescent protein-labeled antigen.

Conclusions

Nanosphere and antigen uptake by monocytes can be directly correlated to the chemistry of the nanosphere. These results demonstrate the importance of choosing polyanhydride chemistries that facilitate enhanced interactions with antigen presenting cells that are necessary in the initiation of efficacious immune responses.

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Acknowledgments

B.N. and M.J.W. acknowledge financial support from the US Department of Defense—Office of Naval Research (ONR Award no. N00014-06-1-1176) and the Grow Iowa Values Fund. B.H.B. acknowledges startup funds provided by Iowa State University-College of Veterinary Medicine and the Office of Biotechnology. B.D.U acknowledges financial support from the Aileen S. Andrew Foundation. The authors acknowledge useful discussions with Dr. Amanda Ramer-Tait and Jenny Wilson-Welder. B.N. dedicates this work to Nicholas A. Peppas on the wonderful occasion of his sixtieth birthday.

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Authors and Affiliations

  1. Department of Chemical and Biological Engineering, Iowa State University, Ames, IOWA, 50011, USA

    Bret D. Ulery & Balaji Narasimhan

  2. Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IOWA, 50011, USA

    Yashdeep Phanse, Avanti Sinha, Michael J. Wannemuehler & Bryan H. Bellaire

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  1. Bret D. Ulery
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  2. Yashdeep Phanse
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Correspondence to Balaji Narasimhan or Bryan H. Bellaire.

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Ulery, B.D., Phanse, Y., Sinha, A. et al. Polymer Chemistry Influences Monocytic Uptake of Polyanhydride Nanospheres. Pharm Res 26, 683–690 (2009). https://doi.org/10.1007/s11095-008-9760-7

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  • DOI: https://doi.org/10.1007/s11095-008-9760-7

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