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Challenges and Future Prospects for the Delivery of Biologics: Oral Mucosal, Pulmonary, and Transdermal Routes

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Abstract

Biologic products are large molecules such as proteins, peptides, nucleic acids, etc., which have already produced many new drugs for clinical use in the last decades. Due to the inherent challenges faced by biologics after oral administration (e.g., acidic stomach pH, digestive enzymes, and limited permeation through the gastrointestinal tract), several alternative routes of administration have been investigated to enable sufficient drug absorption into systemic circulation. This review describes the buccal, sublingual, pulmonary, and transdermal routes of administration for biologics with relevant details of the respective barriers. While all these routes avoid transit through the gastrointestinal tract, each has its own strengths and weaknesses that may be optimal for specific classes of compounds. Buccal and sublingual delivery enable rapid drug uptake through a relatively permeable barrier but are limited by small epithelial surface area, stratified epithelia, and the practical complexities of maintaining a drug delivery system in the mouth. Pulmonary delivery accesses the highly permeable and large surface area of the alveolar epithelium but must overcome the complexities of safe and effective delivery to the alveoli deep in the lung. Transdermal delivery offers convenient access to the body for extended-release delivery via the skin surface but requires the use of novel devices and formulations to overcome the skin’s formidable stratum corneum barrier. New technologies and strategies advanced to overcome these challenges are reviewed, and critical views in future developments of each route are given.

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Acknowledgments

J.O. Morales and M. Montenegro-Nicolini thank the financial support from FONDECYT 11130235 and FONDAP 15130011.

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Authors and Affiliations

  1. Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, 8380494, Santiago, Chile

    Javier O. Morales & Miguel Montenegro-Nicolini

  2. Advanced Center for Chronic Diseases (ACCDiS), 8380494, Santiago, Chile

    Javier O. Morales

  3. Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas, 78712, USA

    Kristin R. Fathe, Ashlee Brunaugh, Silvia Ferrati & Hugh D. C. Smyth

  4. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA

    Song Li & Mark R. Prausnitz

  5. Public Health Institute of Chile, 7780050, Santiago, Chile

    Miguel Montenegro-Nicolini

  6. Chemical & Petroleum Engineering Department, Sharif University of Technology, Tehran, Iran

    Zeynab Mousavikhamene

  7. College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, 87131, USA

    Jason T. McConville

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  1. Javier O. Morales
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Morales, J.O., Fathe, K.R., Brunaugh, A. et al. Challenges and Future Prospects for the Delivery of Biologics: Oral Mucosal, Pulmonary, and Transdermal Routes. AAPS J 19, 652–668 (2017). https://doi.org/10.1208/s12248-017-0054-z

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