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Bio-inspired, bioengineered and biomimetic drug delivery carriers

Nature Reviews Drug Discovery volume 10, pages 521–535 (2011)Cite this article

Subjects

Key Points

  • There are various challenges and limitations associated with the delivery of free drugs. These include poor solubility, poor stability, unwanted toxicity and/or an inability to cross cell membranes.

  • Although there have been considerable advances in the development of synthetic drug carriers, it has emerged that natural carrier systems — such as those used by bacteria, viruses and various cells within the body — have the potential to be therapeutically exploited and may be highly effective in addressing these challenges.

  • Several strategies have been proposed that are based on the engineering of bacteria and viruses for therapeutic functions, including recombinant bacteria for protein delivery, tumour-targeting bacteria for chemotherapeutic applications, and viral gene vectors and virus-like particles for vaccination.

  • Pathogens such as bacteria and viruses induce diseases by evading immune responses and inducing favourable interactions with target cells, a mechanism that bears a striking resemblance to the action of many drug delivery carriers. Several synthetic carriers attempt to mimic these features to enhance their therapeutic function, especially for vaccination.

  • Various types of cells — including red blood cells, macrophages, dendritic cells and stem cells — have been used as carriers or they have inspired the design of new carriers.

  • Technologies that take advantage of the complex structural features that are seen in biological systems as well as precision engineering and production (as seen in synthetic carriers) have great potential for the advancement of effective drug delivery strategies.

Abstract

Synthetic carriers such as polymer and lipid particles often struggle to meet clinical expectations. Natural particulates — that range from pathogens to mammalian cells — are therefore worth examining in more depth, as they are highly optimized for their specific functions in vivo and possess features that are often desired in drug delivery carriers. With a better understanding of these biological systems, in conjunction with the availability of advanced biotechnology tools that are useful for re-engineering the various natural systems, researchers have started to exploit natural particulates for multiple applications in the delivery of proteins, small interfering RNA and other therapeutic agents. Here, we review the natural drug delivery carriers that have provided the basis and inspiration for new drug delivery systems.

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Figure 1: Bioengineered pathogens for drug delivery.
Figure 2: Virus-mimicking synthetic drug carriers.
Figure 3: Bioengineered eukaryotic cells for drug delivery.
Figure 4: Cell-mimicking synthetic drug particles.
Figure 5: Bioengineered, bio-inspired and biomimetic systems.

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Acknowledgements

D.E.D. acknowledges support from the US National Science Foundation (University of Pennsylvania's Materials Research Science and Engineering Center and Nano/Bio Interface Center) and the US National Institutes of Health (National Institute of Biomedical Imaging and Bioengineering and National Heart, Lung and Blood Institute). D.J.I. is an investigator of the Howard Hughes Medical Institute, and acknowledges support from the US National Institutes of Health (CA140476) and the US Department of Defense (Prostate Cancer Research Program). J.-W.Y. and S.M. acknowledge support from the University of California Discovery program.

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Authors and Affiliations

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

    Jin-Wook Yoo & Samir Mitragotri

  2. College of Pharmacy, Chosun University, 501–759, Gwangju, South Korea

    Jin-Wook Yoo

  3. Department of Materials Science & Engineering, Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Darrell J. Irvine

  4. Ragon Institute of MGH, MIT and Harvard, Boston, 02139, Massachusetts, USA

    Darrell J. Irvine

  5. Howard Hughes Medical Institute, Chevy Chase, 20815, Maryland, USA

    Darrell J. Irvine

  6. Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Dennis E. Discher

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  4. Samir Mitragotri
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Correspondence to Samir Mitragotri.

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Glossary

Free drugs

Drugs that are not modified or processed to improve their physicochemical properties and pharmacokinetics profile.

Natural tropisms

The natural movement of a biological organism preferentially towards specific cell types in response to environmental stimuli.

Attenuated bacteria

Viable bacteria with a reduced degree of pathogenicity.

Photothermal therapy

A novel therapeutic use of electromagnetic radiation (for example, infrared) that is proposed to treat various medical conditions, including cancer, by producing heat to kill target cells.

Capsid

The protein shell of a virus that encloses and protects the genetic material inside the virus.

Reticuloendothelial system

(RES). A component of the immune system, which consists of phagocytic cells that are capable of engulfing abnormal cells) and foreign substances. Also called the mononuclear phagocyte system.

Tumour-associated macrophages

(TAMs). Macrophages that are derived from peripheral blood monocytes and recruited into the tumour stroma. Following their activation, TAMs release various growth factors, cytokines and inflammatory mediators for tumour progression.

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Yoo, JW., Irvine, D., Discher, D. et al. Bio-inspired, bioengineered and biomimetic drug delivery carriers. Nat Rev Drug Discov 10, 521–535 (2011). https://doi.org/10.1038/nrd3499

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