The Long Road to Getting Nanomedicine in the Clinic

By Dr. Priyom Bose, Ph.D.Reviewed by Frances BriggsMay 7 2026

Nanomedicine's Therapeutic Potential
Translational Barriers in Nanomedicine: From Bench to Clinic
Future Outlook
References and Future Readings

Nanomedicine has long promised more precise treatment. In principle, engineered nanoparticles can deliver drugs directly to diseased cells, reduce damage to healthy tissue, and improve outcomes in cancer and chronic disease. Yet despite billions of dollars in research, clinical translation has been much slower than many researchers first anticipated. 

Image Credit: PeopleImages/Shutterstock.com

That slow progress reflects a combination of biological, regulatory, manufacturing, and safety challenges. It also reflects persistent gaps in understanding how nanoscale materials behave in the human body.

Saving this article for later? Download a PDF here.

Nanomedicine's Therapeutic Potential

Nanomedicine is a branch of medicine that uses nanoscale materials to diagnose, treat, and prevent disease.¹ Scientists design nanoparticles and other nanoscale carriers to interact with biological systems at the molecular level. This can support more precise and effective therapeutic and diagnostic strategies than conventional approaches allow.

When taken to the nanoscale, materials exhibit physicochemical properties that differ from those of their bulk counterparts. As particle size decreases, the surface area-to-volume ratio increases, which can improve the solubility and dissolution of poorly soluble drugs.

Encapsulating drugs in nanoparticles can change their pharmacokinetic behavior by prolonging circulation time, protecting against enzymatic degradation, and improving bioavailability. Nanoparticles can also be engineered for controlled release or targeted delivery to specific tissues, reducing off-target toxicity and improving therapeutic outcomes.²

Since 1985, several nanomedicine platforms have received approval from regulatory agencies such as the U.S. Food and Drug Administration and the European Medicines Agency. These include liposomes, lipid nanoparticles, nano-solid dispersions, and nanocrystals used to treat diseases ranging from infectious respiratory conditions to hematological malignancies and rare neurological disorders.³

Table 1: Examples of nanomedicines approved by regulatory bodies for various conditions.⁴

Translational Barriers in Nanomedicine: From Bench to Clinic

In the last decade, over 100,000 articles have been published promising new nanomedicines, yet fewer than 90 products have been approved globally, and less than 0.1 % of research has reached clinics.⁵

To successfully translate nanomedicine to the clinic, there must be alignment among scientific design, manufacturing capability, and regulatory strategy.

There are four key factors that determine clinical success or failure of nanomedicines:⁵

Biological Determinants

In cancer nanomedicine, over-reliance on the enhanced permeability and retention effect remains a major translational weakness.⁶ The EPR effect is highly variable across tumor types and patient populations. Irregular vascular architecture, elevated interstitial fluid pressure, and stromal density can all reduce nanoparticle extravasation and intratumoral penetration.

These variables weaken the predictive value of preclinical models. They also support a move toward active targeting ligands, stimuli-responsive release mechanisms, and EPR-independent delivery strategies guided by patient-specific transport biomarkers.

Experts predict nanomedicine's future in 2026

Safety and Biocompatibility

The safety profile of nanomedicines is shaped by several interacting factors. At the physicochemical level, surface charge density, protein corona dynamics, and degradation kinetics are important determinants of toxicity. These properties can influence mechanisms such as reactive oxygen species generation, lysosomal membrane permeabilization, and dysregulation of innate immune signaling.

At the immunological level, PEGylation-induced anti-polyethylene glycol antibody seroconversion can pose a clinically significant risk. It may trigger hypersensitivity reactions and accelerated blood clearance, both of which reduce therapeutic exposure.

The growing prevalence of pre-existing anti-PEG antibodies in the general population makes this issue all the more important. For that reason, immunogenicity risk management should be built into clinical trial design.

Manufacturing and Scalability

One of the main manufacturing challenges is translating laboratory-scale synthesis into Good Manufacturing Practice-compliant processes that are reproducible and scalable. Critical quality attributes such as particle size, polydispersity index, surface charge, and drug encapsulation efficiency must be tightly controlled – even inter-batch size deviations of just 10 nm can produce clinically significant changes in pharmacokinetic and biodistribution profiles.

Conventional batch manufacturing methods are often limited in their ability to achieve that level of size control at scale. Another problem is the limited mechanistic understanding of how process parameters affect critical quality attributes and, in turn, in vivo performance.

Progress here will require platform-specific Chemistry, Manufacturing, and Controls guidance for emerging manufacturing methods, including microfluidic-based lipid nanoparticle production. It could also require in-process analytical tools that support batch-to-batch consistency and quality-by-design implementation.⁵

Regulatory Landscape

Physicochemical parameters such as hydrodynamic diameter, surface charge, zeta potential, morphology, and surface functionalization are primary determinants of in vivo biofate. These properties influence opsonization, reticuloendothelial system clearance, plasma protein corona formation, and intracellular trafficking.

The lack of harmonized analytical frameworks for these properties complicates both formulation development and regulatory review. The absence of robust in vitro-in vivo correlations also limits the rational design of nanoparticles with predictable pharmacokinetic behavior.

Both the FDA and EMA apply risk-based, case-by-case evaluation frameworks to account for the structural and functional heterogeneity of nanomedicine platforms. Their requirements focus on detailed CMC documentation, in-depth physicochemical characterization, and non-clinical safety packages.

However, the lack of internationally harmonized regulatory standards creates major variation in data requirements across jurisdictions. This can prolong approval timelines and restrict patient access.^5,6

Image Credit: Gorodenkoff/Shutterstock.com

Future Outlook

Emerging technologies may help improve the pace of nanomedicine translation.  Artificial intelligence and machine learning are creating new approaches for formulation development and quality control, optimizing physicochemical properties, predicting product failures, and enhancing process understanding.⁷ 

Combined with continuous manufacturing and advanced process monitoring tools, these methods may support more automated, reliable nanomedicine production. This could place nanomedicine at the forefront of modern pharmaceutical manufacturing. Yet, these ideas are young, and it is not clear how well they can be implemented, or with how much success.

References and Future Readings

1. Wen F, Wang L, Li X, Zhao J, Xu T, Zhu J, Ma L, Wang X. Precision Nanomedicine for Cancer: Innovations, Strategies, and Translational Challenges. Onco Targets Ther. 2025;18:1125-1148. DOI:10.2147/OTT.S550104, https://www.dovepress.com/precision-nanomedicine-for-cancer-innovations-strategies-and-translati-peer-reviewed-fulltext-article-OTT.
2. Rahman MA, Jalouli M, Yadab MK, Al-Zharani M. Progress in Drug Delivery Systems Based on Nanoparticles for Improved Glioblastoma Therapy: Addressing Challenges and Investigating Opportunities. Cancers. 2025; 17(4):701. DOI:10.3390/cancers17040701, https://www.mdpi.com/2072-6694/17/4/701
3. Jia Y, Jiang Y, He Y, Zhang W, Zou J, Magar KT, Boucetta H, Teng C, He W. Approved Nanomedicine against Diseases. Pharmaceutics. 2023;15(3):774. DOI:10.3390/pharmaceutics15030774, https://www.mdpi.com/1999-4923/15/3/774.
4. Zhang X, et al. Navigating translational research in nanomedicine: A strategic guide to formulation and manufacturing. Int J Pharm. 2025; 671, 125202. DOI:10.1016/j.ijpharm.2025.125202, https://doi.org/10.1016/j.ijpharm.2025.125202
5. Herdiana Y. Bridging the Gap: The Role of Advanced Formulation Strategies in the Clinical Translation of Nanoparticle-Based Drug Delivery Systems. Int J Nanomedicine. 2025;20:13039-13053. DOI:10.2147/IJN.S554821, https://www.dovepress.com/bridging-the-gap-the-role-of-advanced-formulation-strategies-in-the-cl-peer-reviewed-fulltext-article-IJN.
6. Liu Y, Zhang Y, Li H, Hu TY. Recent advances in the bench-to-bedside translation of cancer nanomedicines. Acta Pharm Sin B. 2025;15(1):97-122. DOI:10.1016/j.apsb.2024.12.007, https://www.sciencedirect.com/science/article/pii/S2211383524004647?via%3Dihub.
7. Chou WC, Canchola A, Zhang F, Lin Z. Machine Learning and Artificial Intelligence in Nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2025;17(4):e70027. DOI:10.1002/wnan.70027, https://wires.onlinelibrary.wiley.com/doi/10.1002/wnan.70027.

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.