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Inhalable materials and biologics for lung defence and drug delivery

Nature Reviews Materials volume 11, pages 90–116 (2026)Cite this article

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Abstract

Airway mucus has a crucial role in protecting against inhaled pathogens and regulating water homeostasis, but it can also diminish the efficacy of therapeutic pulmonary delivery. Recent development in inhalable materials and biologics has introduced strategies to modify mucus properties, strengthening mucosal protection, advancing drug delivery and targeting and supporting effective water regulation. In this Review, we thoroughly examine the structure and function of airway mucus, along with the challenges and opportunities it presents for inhaled treatments. We explore new methods that enhance the protective role of mucus through physical reinforcement, pathogen neutralization, muco-trapping and rehydration, as well as strategies that overcome the mucus barrier to improve drug delivery, including physical modulation, mucoadhesive design, muco-penetrating design, mucolytics and active targeting. Finally, we discuss the clinical implications of these promising strategies, emphasizing the need to balance mucosal function with optimized therapeutic delivery. We seek to explore prospective ways to improve inhalation therapies for both infectious and chronic lung diseases by reviewing recent progress in inhalable materials and biologics.

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Fig. 1: Airway mucus structure and function.
Fig. 2: Timeline of inhalable materials and biologics development for mucus barrier enhancement and pulmonary drug delivery.
Fig. 3: Strategies to enhance mucus barrier function.
Fig. 4: Physical and biological barriers for pulmonary drug delivery.
Fig. 5: Strategies for material and biologic pulmonary delivery, categorized by delivered agent type for each strategy.
Fig. 6: Clinical implications and outlook of inhalable materials and biologics of next decade.

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Acknowledgements

K.C. thanks grant support from the US National Institute of Health and American Heart Association. S.W.Z. and K.C. also thank C. Kaganov and her late husband A.L. Kaganov for their generous support that helped to make this work possible.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Columbia University, New York, NY, USA

    Savannah Weihang Zhang  (张苇杭) & Ke Cheng

  2. Center for Nanomedicine, Johns Hopkins University Medical School, Baltimore, MD, USA

    David A. Edwards

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

    David A. Edwards

  4. Sensory Cloud, Boston, MA, USA

    David A. Edwards

  5. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Robert Langer

  6. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Robert Langer

  7. Seymour, Paul and Gloria Milstein Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA

    Ke Cheng

  8. Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA

    Ke Cheng

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Contributions

S.W.Z. searched and summarized literature for the article. All authors contributed substantially to the discussion. S.W.Z. drafted the article. All authors edited and approved the manuscript before submission.

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Correspondence to Robert Langer or Ke Cheng.

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Competing interests

D.A.E. is a co-founder of Sensory Cloud. K.C. is a co-founder of BreStem Therapeutics. A complete list of R.L.’s competing interests is provided in the Supplementary information. S.W.Z. declares no competing interests.

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Zhang, S.W., Edwards, D.A., Langer, R. et al. Inhalable materials and biologics for lung defence and drug delivery. Nat Rev Mater 11, 90–116 (2026). https://doi.org/10.1038/s41578-025-00841-y

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