Nominal Dose Does Not Equal Effective Dose
Preclinical studies of inhaled therapies, including those using nanotechnology, often report the total dose administered to animals, such as the amount delivered by a nebulizer or inhaler. However, significant portions can be lost due to device retention, exhalation, or deposition in the upper airways.
The comment stresses that the critical factor is the dose that reaches lung tissue, and particularly where in the lung the drug deposits. Without precise measurement, comparisons across animal models and predictions of human outcomes remain uncertain.
Implications for Translational Research
Focusing on lung-deposited dose allows for:
- Consistent comparisons across models: Different species have distinct airway structures and breathing patterns, making measurements of actual lung dose essential to align therapeutic exposure.
- Improved prediction of efficacy and safety: The fraction of drug reaching the lung determines both therapeutic and potential side effects.
- Better understanding of treatment outcomes: Accurate dosimetry helps identify whether treatment failure is due to drug properties or delivery limitations.
Advancing Therapeutic Development
The comment suggests strategies to improve drug development and clinical translation:
- Direct measurement of lung-deposited dose rather than relying on nominal dose.
- Assessment of deposition patterns to determine where drugs accumulate in the lung.
- Design of clinical trials that reflect precise preclinical exposures.
- Tailored therapies targeting specific lung regions depending on the disease.
- Transparent reporting to enhance reproducibility and reliability of findings.
Precise dosimetry is particularly relevant for complex therapies such as inhaled biologics, nanomedicines, and mRNA vaccines. Accurate measurement of lung-deposited doses could accelerate the development of more effective treatments including asthma, COPD, lung fibrosis, and chronic lung infections.
The comment was authored by Dr. Lin Yang, together with Dr. Otmar Schmid (group leader) and Dr. Lianyong Han from the Institute of Lung Health and Immunity (LHI) at Helmholtz Munich, and Prof. Chunying Chen from the National Center for Nanoscience and Technology in China.
Original Publication
Yang et al., 2025: Precision dosimetry in pulmonary drug delivery. Nature Reviews Bioengineering. DOI: 10.1038/s44222-025-00356-9
