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Principles of nanoparticle design for overcoming biological barriers to drug delivery

Nature Biotechnology volume 33, pages 941–951 (2015)Cite this article

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Abstract

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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Figure 1: Framework of sequential biological barriers to nanoparticle drug delivery.
Figure 2: Strategies for nanoparticle biomimicry for MPS avoidance and prolonged circulation.
Figure 3: Nanoparticle flow, margination and adhesive properties in blood vessels are dependent on particle size and geometry.
Figure 4: Determinants of enhanced permeability of nanoparticles into tumor tissues.
Figure 5: Nanoparticle size, shape and surface charge dictate biodistribution among the different organs including the lungs, liver, spleen and kidneys.

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Acknowledgements

M.F. is grateful for the Ernest Cockrell Jr. Distinguished Endowed Chair in the Department of Nanomedicine at the Houston Methodist Research Institute. The authors acknowledge financial support from Department of Defense grant W81XWH-12-1-0414, and US National Institutes of Health grants NIH U54CA143837 and NIH U54CA151668. E.B. is grateful for the support of the Susan G. Komen Breast Cancer Foundation (grant KG101394). The authors are grateful for the assistance of F.E. Cara, V. Segura-Ibarra and Suhong Wu in manuscript preparation. M.G. Landry is acknowledged for manuscript schematics.

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Authors and Affiliations

  1. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA

    Elvin Blanco, Haifa Shen & Mauro Ferrari

  2. Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA

    Haifa Shen

  3. Department of Medicine, Weill Cornell Medical College, New York, New York, USA

    Mauro Ferrari

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  1. Elvin Blanco
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  2. Haifa Shen
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  3. Mauro Ferrari
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Correspondence to Mauro Ferrari.

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Blanco, E., Shen, H. & Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol 33, 941–951 (2015). https://doi.org/10.1038/nbt.3330

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