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  • Review Article
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Non-invasive delivery strategies for biologics

Nature Reviews Drug Discovery volume 18, pages 19–40 (2019)Cite this article

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Abstract

Biologics now constitute a significant element of available medical treatments. Owing to their clinical and commercial success, biologics are a rapidly growing class and have become a dominant therapeutic modality. Although most of the successful biologics to date are drugs that bear a peptidic backbone, ranging from small peptides to monoclonal antibodies (~500 residues; 150 kDa), new biologic modalities, such as nucleotide-based therapeutics and viral gene therapies, are rapidly maturing towards widespread clinical use. Given the rise of peptides and proteins in the pharmaceutical landscape, tremendous research and development interest exists in developing less-invasive or non-invasive routes for the systemic delivery of biologics, including subcutaneous, transdermal, oral, inhalation, nasal and buccal routes. This Review summarizes the current status, latest updates and future prospects for such delivery of peptides, proteins and other biologics.

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Figure 1: Subcutaneous barriers, products and new approaches.
Figure 2: Transdermal barriers, products and new approaches.
Figure 3: Oral barriers, products and new approaches.
Figure 4: Inhalable barriers, products and new approaches.

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Acknowledgements

S.M. acknowledges support from the National Institutes of Health, Grant R01DK097379.

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Authors and Affiliations

  1. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Aaron C. Anselmo

  2. Biologics Drug Product Development, Sanofi Research and Development, Framingham, MA, USA

    Yatin Gokarn

  3. John A. Paulson School of Engineering and Applied Sciences, Wyss Institute of Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA

    Samir Mitragotri

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Correspondence to Samir Mitragotri.

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Competing interests

S.M. is a shareholder of, consultant to and recipient of research grants from several drug delivery, pharmaceutical and biotechnology companies, including those active in the general area of research discussed in this article. The authors are inventors on several patents in the field of drug delivery and formulations that are owned by their current or former employers. The views presented here should not be considered as endorsements of any specific product or company.

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Current clinical landscape for subcutaneous biologics (PDF 55 kb)

Glossary

PEGylation

The attachment of polyethylene glycol to a biologic to shield it from the immune system and thereby increase its half-life.

First-pass metabolism

The biological process by which the delivered biologic is metabolized by the liver or gastrointestinal tract before reaching systemic circulation.

Iontophoresis

The application of an electrical current to a biologic formulation at the surface of the skin. The current improves transport of the biologic across the skin via electrophoresis.

Liposomes

Phospholipid-based nanoparticles with tuneable physicochemical parameters that are designed to encapsulate and deliver biologics.

Excipients

Inactive substances found in pharmaceutical formulations. Excipients can include absorption enhancers, stability enhancing agents or anticaking agents.

Pulmonary surfactant

Lipid and protein secreted by type II alveolar cells that adsorb to the air–water interface in the lungs. Pulmonary surfactant is a required biological fluid that reduces the surface tension in lung alveoli to facilitate inhalation and exhalation.

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Anselmo, A., Gokarn, Y. & Mitragotri, S. Non-invasive delivery strategies for biologics. Nat Rev Drug Discov 18, 19–40 (2019). https://doi.org/10.1038/nrd.2018.183

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