Why Drug Delivery Remains a Major Challenge
How Nanoparticles Can Improve Drug Delivery
The Opportunity of Precision Targeting
Why Inhaled Delivery Is Attractive
Supporting Emerging RNA and Gene Therapies
Key Challenges for Clinical Implementation
Conclusion
References and Further Reading
Treating lung disease is often limited not by the drug's effectiveness, but by the challenge of getting it to the right place at the right concentration. Recent advances in precision nanomedicine suggest that nanoparticles may help overcome many of the biological barriers that have historically limited respiratory therapies.1 Researchers are increasingly exploring whether engineered nanocarriers can improve the delivery of drugs, genes, and RNA-based therapies to specific cells within the lung while reducing unwanted effects elsewhere in the body.
Image Credit: Jo Panuwat D/Shutterstock.com
Why Drug Delivery Remains a Major Challenge
The lungs appear to be an ideal treatment target because they are directly accessible through inhalation. However, their complex anatomy and sophisticated defense mechanisms make effective drug delivery surprisingly difficult. Therapeutic agents must navigate mucus layers, airway branching structures, immune surveillance systems, and cellular barriers before reaching their intended targets.
Many conventional medicines penetrate poorly into diseased tissues or distribute widely throughout the body after administration. This can reduce therapeutic effectiveness while increasing the risk of systemic side effects. Typically, less than 1% of the injected dose reaches the target tissue.1,2
The challenge is even greater for newer therapeutic approaches such as messenger RNA (mRNA), where these molecules are often unstable and have a short half-life, which can limit their ability to reach their targets.3
Want to save this article for later? Click here.
How Nanoparticles Can Improve Drug Delivery
Nanoparticles are engineered structures that typically measure between 1 and 100 nanometres. At this scale, materials exhibit unique characteristics that can be exploited for medical applications.
One of their most important functions is protecting therapeutic cargo during transport. Fragile molecules such as mRNA can be enclosed within lipid nanoparticles to protect the nucleic acids from degradation and allow cellular uptake.3 This protective effect can significantly improve the stability and bioavailability of therapeutics before they reach diseased tissue.1
Nanoparticles can also be engineered to release their contents in a controlled manner. Rather than releasing a drug immediately after administration, the carrier can be designed to respond to intracellular/microenvironmental stimuli such as pH, hypoxia, specific enzymes, temperature, magnetic fields, and light via bio-responsive moieties.4 This enables treatment to be concentrated at the site of disease while reducing exposure to healthy tissues.
Another advantage is their ability to facilitate cellular uptake when a cationic polymer coating such as polyethyleneimine (PEI) is used to aid drug delivery.5 Many therapeutic molecules cannot cross cell membranes efficiently on their own. Nanoparticles are widely used to deliver various therapeutic agents to target locations due to their unique physicochemical properties and ability to overcome lysosomal barriers.5
The Opportunity of Precision Targeting
A major goal of precision nanomedicine is tissue and cell-specific targeting. Rather than delivering a drug broadly throughout the respiratory system, researchers aim to direct therapies toward the cells driving disease.
For instance, decorating nanoparticle surfaces with functional ligands that selectively bind to receptors unique to target cells ensures cellular specificity.1 This strategy may improve local drug accumulation while sparing healthy tissue. Similarly, nanoparticles can selectively localize within tumor lung tissue and myeloid cells adjacent to fibrotic areas via their respective folate receptors.1
Asthma presents another interesting application. Many existing asthma treatments rely on inhaled corticosteroids that affect broad regions of the respiratory tract. Future nanoparticle systems could deliver therapies more selectively to inflammatory immune cells, potentially improving efficacy while lowering side effects. These approaches remain under active investigation, but their rationale reflects the wider trend toward personalized medicine.1
Why Inhaled Delivery Is Attractive
One of the most promising aspects of pulmonary nanomedicine is the possibility of inhalation-based administration.
Delivering nanoparticles directly through the airways may offer several advantages over intravenous injection. Inhaled therapies can potentially achieve high local concentrations while requiring smaller overall doses.
Direct delivery also reduces first-pass metabolism and may limit systemic exposure.1,6 For diseases primarily located within the lungs, this localized approach is particularly appealing.
However, inhalation introduces its own challenges. Particle size, shape, surface charge, and aerodynamic properties must be carefully controlled to ensure deposition in the desired regions of the respiratory tract.1
Particles that are too large may become trapped in the upper airways, while those that are too small may be exhaled before deposition occurs.1 Furthermore, mucociliary clearance mechanisms continuously work to remove foreign materials from the lungs.1,7
Supporting Emerging RNA and Gene Therapies
The success of lipid nanoparticle technology in vaccine delivery has increased interest in applying similar approaches to pulmonary diseases.
Many RNA and gene-based therapies depend on efficient delivery systems because naked nucleic acids are highly vulnerable to degradation.
Nanocarriers can encapsulate mRNA and other genetic cargo while improving transport to target cells.3 This capability has relevance for inherited respiratory disorders, inflammatory diseases, and certain cancers.
Without advanced delivery platforms, many of these therapies would struggle to achieve meaningful clinical benefit. Consequently, improvements in nanoparticle design are increasingly viewed as a critical enabling technology rather than merely a supporting component of treatment development.1,3
Key Challenges for Clinical Implementation
Despite impressive progress, significant barriers remain before precision nanomedicine becomes a routine clinical tool.
While nanoparticles can improve drug delivery, researchers must demonstrate that they do not cause unacceptable toxicity, chronic inflammation, or unintended accumulation in organs over long periods.
Another challenge involves translating results from animal studies to humans.8 Translation from animal studies to successful human therapies remains a major challenge; an umbrella review found that although many animal-tested interventions progressed to human studies, only around 5% ultimately obtained regulatory approval.
Manufacturing presents an additional challenge, as nanoparticles must be produced consistently at scale while maintaining strict control over size and reproducibility.9 Addressing these technical and practical challenges is essential for the successful translation of nanomedicine from research to clinical application.
Conclusion
Nanoparticles will not eliminate every challenge associated with treating lung disease, but they offer powerful tools for overcoming some of the most persistent drug-delivery barriers.
Because nanocarriers can protect therapeutic cargo, improve cellular uptake, enable controlled release, and support tissue-specific targeting, nanomedicine has the potential to make treatments more precise and effective.
Research has highlighted how these technologies are advancing across a wide range of pulmonary diseases.1 Yet, clinical adoption will depend on demonstrating long-term safety, reproducible manufacturing, regulatory compliance, and consistent performance in human patients. If these hurdles can be addressed, precision nanomedicine may help transform how respiratory diseases are treated in the coming decades.
References and Further Reading
- Deng, Z., et al. (2026). Precision nanomedicine for pulmonary diseases: from molecular targeting to clinical translation. Signal Transduction and Targeted Therapy, 11, 358. https://doi.org/10.1038/s41392-026-02982-0
- Zelepukin, I. V., Shevchenko, K. G. & Deyev, S. M. (2024). Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery. Nat. Commun. 15, 4366. https://doi.org/10.1038/s41467-024-48838-5
- Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021). Lipid nanoparticles for mRNA delivery. Nature Reviews Materials, 6(12), 1078-1094. https://doi.org/10.1038/s41578-021-00358-0
- Yang, J., des Rieux, A., & Malfanti, A. (2025). Stimuli-Responsive Nanomedicines for the Treatment of Non-cancer Related Inflammatory Diseases. ACS Nano, 19(16), 15189-15219. https://doi.org/10.1021/acsnano.5c00700
- Wang, X., Li, H., Chen, C., & Liang, Z. (2025). Understanding of endo/lysosomal escape of nanomaterials in biomedical application. Smart Medicine. 3(4), 2751-4587. https://doi.org/10.1002/smo.20240017
- Deng, Z., et al. (2021) Nanoparticle delivery systems with cell-specific targeting for pulmonary diseases. Am. J. Respir. Cell Mol. Biol. 64, 292–307. https://doi.org/10.1165/rcmb.2020-0306TR
- Hill, D. B., Button, B., Rubinstein, M. & Boucher, R. C. (2022). Physiology and pathophysiology of human airway mucus. Physiol. Rev. 102, 1757–1836. https://doi.org/10.1152/physrev.00004.2021
- Ineichen, B. V., et al. (2024). Analysis of animal-to-human translation shows that only 5% of animal-tested therapeutic interventions obtain regulatory approval for human applications. PLOS Biology, 22(6), e3002667. https://doi.org/10.1371/journal.pbio.3002667
- Delfino, C. S. C., et al. (2025). Scaling nanopharmaceutical production for personalized medicine: challenges and strategies. Journal of Nanoparticle Research, 27. https://doi.org/10.1007/s11051-025-06293-3
Disclaimer: The views expressed here are those of the author expressed in their private capacity and do not necessarily represent the views of AZoM.com Limited T/A AZoNetwork the owner and operator of this website. This disclaimer forms part of the Terms and conditions of use of this website.