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Materials and methods for delivery of biological drugs

Nature Chemistry volume 8, pages 997–1007 (2016)Cite this article

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Abstract

Biological drugs generated via recombinant techniques are uniquely positioned due to their high potency and high selectivity of action. The major drawback of this class of therapeutics, however, is their poor stability upon oral administration and during subsequent circulation. As a result, biological drugs have very low bioavailability and short therapeutic half-lives. Fortunately, tools of chemistry and biotechnology have been developed into an elaborate arsenal, which can be applied to improve the pharmacokinetics of biological drugs. Depot-type release systems are available to achieve sustained release of drugs over time. Conjugation to synthetic or biological polymers affords long circulating formulations. Administration of biological drugs through non-parenteral routes shows excellent performance and the first products have reached the market. This Review presents the main accomplishments in this field and illustrates the materials and methods behind existing and upcoming successful formulations and delivery strategies for biological drugs.

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Figure 1: Biodegradable organic polymers can be used to engineer implantable depots for controlled release of biological drugs over extended periods of time.
Figure 2: Assembly of surface coatings.
Figure 3: Conjugation of biological drugs with synthetic non-ionic water-soluble polymers.
Figure 4: Recombinant techniques constitute a highly successful approach to engineer derivatives of biological drugs with markedly extended blood residence time.
Figure 5: Physiological recycling of albumin and immunoglobulins.
Figure 6: Examples of non-invasive drug administration routes.
Figure 7: Transdermal administration of biological drugs.

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Acknowledgements

We wish to thank Anton A.A. Smith, Lucy Kate Ladefoged, Cecilie Domar (Aarhus University), Helga Jonuschat (InnoZ), Uli Binder and Arne Skerra (XL-protein) for assistance in preparation of the illustrative material, Søren Ostegaard and Stephen Buckley (Novo Nordisk) for stimulating discussions. We also wish to acknowledge financial support from: the Danish Council for Independent Research, Technology and Production Sciences, Denmark (A.N.Z.), the European Research Council Consolidator grant (A.N.Z., ERC-2013-CoG 617336 BTVI), Science Foundation Ireland (A.M.H., SFI/12/RC/2275, SFI/12/RC2278, SFI/12/IP/1408) and the Flight Attendant Medical Research Institute (C.E., FAMRI CIA 130016). The contribution of the COST Actions BM1201 and MP1404 is also acknowledged.

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Authors and Affiliations

  1. Department of Chemistry, Aarhus University, Aarhus, C 8000, Denmark

    Alexander N. Zelikin

  2. iNano Interdisciplinary Nanoscience Centre, Aarhus University, Aarhus, C 8000, Denmark

    Alexander N. Zelikin

  3. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, 2, Ireland

    Carsten Ehrhardt & Anne Marie Healy

  4. Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, 2, Ireland

    Carsten Ehrhardt

  5. Synthesis and Solid State Pharmaceutical Centre, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, 2, Ireland

    Anne Marie Healy

  6. Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity College Dublin, Dublin, 2, Ireland

    Anne Marie Healy

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Correspondence to Alexander N. Zelikin or Carsten Ehrhardt.

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Zelikin, A., Ehrhardt, C. & Healy, A. Materials and methods for delivery of biological drugs. Nature Chem 8, 997–1007 (2016). https://doi.org/10.1038/nchem.2629

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