The evolving landscape of drug products containing nanomaterials in the United States


The Center for Drug Evaluation and Research (CDER) within the US Food and Drug Administration (FDA) is tracking the use of nanotechnology in drug products by building and interrogating a technical profile of products containing nanomaterials submitted to CDER. In this Analysis, data from more than 350 products show an increase in the submissions of drug products containing nanomaterials over the last two decades. Of these, 65% are investigational new drugs, 17% are new drug applications and 18% are abbreviated new drug applications, with the largest class of products being liposomal formulations intended for cancer treatments. Approximately 80% of products have average particle sizes of 300 nm or lower. This analysis identifies several trends in the development of drug products containing nanomaterials, including the relative rate of approvals of these products, and provides a comprehensive overview on the landscape of nanotechnology application in medicine.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Number of nanomaterial product applications submitted to CDER by year.
Figure 2: CDER approved drug products containing nanomaterials by year.
Figure 3: Distribution of nanomaterial use in drug products from 1973 to 2015.
Figure 4
Figure 5: Particle sizes within drug products containing nanomaterials from 1973 to 2015.


  1. 1

    Devalapally, H., Chakilam, A. & Amiji, M. M. Role of nanotechnology in pharmaceutical product development. J. Pharm. Sci. 96, 2547–2565 (2007).

    CAS  Article  Google Scholar 

  2. 2

    Duncan, R. & Gaspar, R. Nanomedicine(s) under the microscope. Mol. Pharmacol. 8, 2101–2141 (2011).

    CAS  Article  Google Scholar 

  3. 3

    Rizzo, L. Y., Theek, B., Storm, G., Kiessling, F. & Lammers, T. Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications. Curr. Opin. Biotechnol. 24, 1159–1166 (2013).

    CAS  Article  Google Scholar 

  4. 4

    Thorley, A. J. & Tetley, T. D. New perspectives in nanomedicine. Pharmacol. Ther. 140, 176–185 (2013).

    CAS  Article  Google Scholar 

  5. 5

    US FDA. Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology (2014).

  6. 6

    Hamburg, M. A. FDA's approach to regulation of products of nanotechnology. Science 336, 299–300 (2012).

    CAS  Article  Google Scholar 

  7. 7

    Lostritto, R. T., Goei, L. & Silvestri, S. L. Theoretical considerations of drug release from submicron oil in water emulsions. J. Parenter. Sci. Technol. 41, 214–219 (1987).

    CAS  Google Scholar 

  8. 8

    U.S. FDA. Guidance, Compliance, & Regulatory Information (2015).

  9. 9

    Tyner, K. M. et al. Product quality for nanomaterials: current U.S. experience and perspective. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 7, 640–654 (2015).

    Article  Google Scholar 

  10. 10

    Brown, P. D. & Patel, P. R. Nanomedicine: a pharma perspective. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 7, 125–130 (2015).

    CAS  Article  Google Scholar 

  11. 11

    Poste, G. et al. Analysis of the fate of systemically administered liposomes and implications for their use in drug delivery. Can. Res. 42, 1412–1422 (1982).

    CAS  Google Scholar 

  12. 12

    Weissig, V., Pettinger, T. K. & Murdock, N. Nanopharmaceuticals (part 1): products on the market. Int. J. Nanomed. 9, 4357–4373 (2014).

    CAS  Article  Google Scholar 

  13. 13

    Letter, T. M. Griseofulvin: a new formulation and some old concerns. Med. Lett. Drugs Ther. 18, 17–18 (1973).

    Google Scholar 

  14. 14

    Wu, Y. et al. Core size determination and structural characterization of intravenous iron complexes by cryogenic transmission electron microscopy. Int. J. Pharm. 505, 167–174 (2016).

    CAS  Article  Google Scholar 

  15. 15

    Jahn, M. R., Mrestani, Y., Langguth, P. & Neubert, R. H. CE characterization of potential toxic labile iron in colloidal parenteral iron formulations using off-capillary and on-capillary complexation with EDTA. Electrophoresis 28, 2424–2429 (2007).

    CAS  Article  Google Scholar 

  16. 16

    US FDA. CDER New Drug Review: 2014 Update (2014).

  17. 17

    Dickson, M. & Gagnon, J. P. The cost of new drug discovery and development. Discov. Med. 4, 172–179 (2004).

    Google Scholar 

  18. 18

    Hay, M., Thomas, D. W., Craighead, J. L., Economides, C. & Rosenthal, J. Clinical development success rates for investigational drugs. Nat. Biotechnol. 32, 40–51 (2014).

    CAS  Article  Google Scholar 

  19. 19

    Committee for the Review of the National Nanotechnology Inititative. Preliminary Comments, Review of the National Nanotechnology Initiative (National Academies Press, 2001);

  20. 20

    DiMasi, J. A., Hansen, R. W. & Grabowski, H. G. The price of innovation: new estimates of drug development costs. J. Health. Econ. 22, 151–185 (2003).

    Article  Google Scholar 

  21. 21

    Evens, R. P. in Drug and Biological Development: From Molecule to Product and Beyond (ed. Evens, R. P.) Ch. 1, 5–32 (Springer, 2007).

    Google Scholar 

  22. 22

    US Congress, Office of Technology Assessment. Government Regulation and Pharmaceutical R&D. 135–168 (US Government Printing Office, 1993).

  23. 23

    Helmus, M. N. The need for rules and regulations. Nat. Nanotech. 2, 333–334 (2007).

    CAS  Article  Google Scholar 

  24. 24

    US Food and Drug Administration. Bioequivalence Recommendations for Specific Products (2010)

  25. 25

    Allen, T. M. & Cullis, P. R. Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev. 65, 36–48 (2013).

    CAS  Article  Google Scholar 

  26. 26

    Jesorka, A. & Orwar, O. Liposomes: technologies and analytical applications. Annu. Rev. Anal. Chem. 1, 801–832 (2008).

    CAS  Article  Google Scholar 

  27. 27

    Barenholz, Y. Doxil®—The first FDA-approved nano-drug: lessons learned. J. Control Rel. 160, 117–134 (2012).

    CAS  Article  Google Scholar 

  28. 28

    Jiang, W., Lionberger, R. & Yu, L. X. In vitro and in vivo characterizations of PEGylated liposomal doxorubicin. Bioanalysis 3, 333–344 (2011).

    CAS  Article  Google Scholar 

  29. 29

    Sercombe, L. et al. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol. 6, 286 (2015).

    Article  Google Scholar 

  30. 30

    Blanco, E. et al. Nanomedicine in cancer therapy: innovative trends and prospects. Cancer Sci. 102, 1247–1252 (2011).

    CAS  Article  Google Scholar 

  31. 31

    Sumer, B. & Gao, J. Theranostic nanomedicine for cancer. Nanomedicine 3, 137–140 (2008).

    Article  Google Scholar 

  32. 32

    Davis, M. E., Chen, Z. G. & Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7, 771–782 (2008).

    CAS  Article  Google Scholar 

  33. 33

    Jain, R. K. & Stylianopoulos, T. Delivering nanomedicine to solid tumors. Nat. Rev. Clin. Oncol. 7, 653–664 (2010).

    CAS  Article  Google Scholar 

  34. 34

    Lammers, T., Hennink, W. E. & Storm, G. Tumour-targeted nanomedicines: principles and practice. Br. J. Cancer 99, 392–397 (2008).

    CAS  Article  Google Scholar 

  35. 35

    Bartlett, J. A. et al. Summary report of PQRI workshop on nanomaterial in drug products: current experience and management of potential risks. AAPS J. 17, 44–64 (2015).

    CAS  Article  Google Scholar 

  36. 36

    Hall, J. B., Dobrovolskaia, M. A., Patri, A. K. & McNeil, S. E. Characterization of nanoparticles for therapeutics. Nanomedicine 2, 789–803 (2007).

    CAS  Article  Google Scholar 

  37. 37

    Tyner, K. & Sadrieh, N. Considerations when submitting nanotherapeutics to FDA/CDER for regulatory review. Methods Mol. Biol. 697, 17–31 (2011).

    CAS  Article  Google Scholar 

  38. 38

    Kobayashi, H. & Brechbiel, M. W. Dendrimer-based macromolecular MRI contrast agents: characteristics and application. Mol. Imaging 2, 1–10 (2003).

    CAS  Article  Google Scholar 

  39. 39

    De Jong, W. H. et al. Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 29, 1912–1919 (2008).

    CAS  Article  Google Scholar 

  40. 40

    Alexis, F., Pridgen, E., Molnar, L. K. & Farokhzad, O. C. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol. Pharm. 5, 505–515 (2008).

    CAS  Article  Google Scholar 

  41. 41

    Gmoshinski, I. V. et al. Nanomaterials and nanotechnologies: methods of analysis and control. Russ. Chem. Rev. 82, 48 (2013).

    Article  Google Scholar 

  42. 42

    Linkov, P., Artemyev, M., Efimov, A. E. & Nabiev, I. Comparative advantages and limitations of the basic metrology methods applied to the characterization of nanomaterials. Nanoscale 5, 8781–8798 (2013).

    CAS  Article  Google Scholar 

  43. 43

    Powers, K. W. et al. Research strategies for safety evaluation of nanomaterials. Part VI. Characterization of nanoscale particles for toxicological evaluation. Toxicol. Sci. 90, 296–303 (2006).

    CAS  Article  Google Scholar 

  44. 44

    Powers, K. W., Palazuelos, M., Moudgil, B. M. & Roberts, S. M. Characterization of the size, shape, and state of dispersion of nanoparticles for toxicological studies. Nanotoxicology 1, 42–51 (2007).

    CAS  Article  Google Scholar 

  45. 45

    Warheit, D. B. How meaningful are the results of nanotoxicity studies in the absence of adequate material characterization? Toxicol. Sci. 101, 183–185 (2008).

    CAS  Article  Google Scholar 

  46. 46

    Bhattacharjee, S. DLS and zeta potential—what they are and what they are not? J. Control Rel. 235, 337–351 (2016).

    CAS  Article  Google Scholar 

  47. 47

    Anderson, W., Kozak, D., Coleman, V. A., Jamting, A. K. & Trau, M. A comparative study of submicron particle sizing platforms: accuracy, precision and resolution analysis of polydisperse particle size distributions. J. Colloid Interface Sci. 405, 322–330 (2013).

    CAS  Article  Google Scholar 

  48. 48

    Boverhof, D. R. & David, R. M. Nanomaterial characterization: considerations and needs for hazard assessment and safety evaluation. Anal. Bioanal. Chem. 396, 953–961 (2009).

    Article  Google Scholar 

  49. 49

    Lin, P.-C., Lin, S., Wang, P. C. & Sridhar, R. Techniques for physicochemical characterization of nanomaterials. Biotechnol. Adv. 32, 711–726 (2014).

    Article  Google Scholar 

  50. 50

    McNeil, S. E. (ed.) Characterization of Nanoparticles Intended for Drug Delivery Vol. 697 (Springer, 2011).

    Google Scholar 

  51. 51

    Sapsford, K. E., Tyner, K. M., Dair, B. J., Deschamps, J. R. & Medintz, I. L. Analyzing nanomaterial bioconjugates: a review of current and emerging purification and characterization techniques. Anal. Chem. 83, 4453–4488 (2011).

    CAS  Article  Google Scholar 

  52. 52

    Grau, M. J., Kayser, O. & Muller, R. H. Nanosuspensions of poorly soluble drugs—reproducibility of small scale production. Int. J. Pharm. 196, 155–159 (2000).

    CAS  Article  Google Scholar 

  53. 53

    Muller, R. H., Jacobs, C. & Kayser, O. Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. Adv. Drug Deliv. Rev. 47, 3–19 (2001).

    CAS  Article  Google Scholar 

  54. 54

    European Commission. Recommendation on the Definition of Nanomaterial (European Commission, 2011).

  55. 55

    Health Canada. Policy Statement on Health Canada's Working Definition for Nanomaterial (Health Canada, 2011).

  56. 56

    ISO. International Organization for Standardization/Technical Specification, Nanotechnologies–Vocabulary–Part 1: Core terms, 2010, ISO/TS 80004-1:2010 (ISO, 2010).

  57. 57

    NSTC/CoT/NSET. National Nanotechnology Initiative Strategic Plan (February 2014).

  58. 58

    Bancos, S., Stevens, D. L. & Tyner, K. M. Effect of silica and gold nanoparticles on macrophage proliferation, activation markers, cytokine production, and phagocytosis in vitro. Int. J. Nanomed. 10, 183–206 (2015).

    CAS  Google Scholar 

  59. 59

    Bancos, S., Tsai, D.-H., Hackley, V., Weaver, J. L. & Tyner, K. M. Evaluation of viability and proliferation profiles on macrophages treated with silica nanoparticles in vitro via plate-based, flow cytometry, and Coulter counter assays. ISRN Nanotechnol. 2012, 454072 (2012).

    Article  Google Scholar 

  60. 60

    Keene, A. M. et al. Tissue and cellular distribution of gold nanoparticles varies based on aggregation/agglomeration status. Nanomedicine 7, 199–209 (2012).

    CAS  Article  Google Scholar 

  61. 61

    Keene, A. M. & Tyner, K. M. Analytical characterization of gold nanoparticle primary particles, aggregates, agglomerates, and agglomerated aggregates. J. Nanopart. Res. 13, 3465–3481 (2011).

    CAS  Article  Google Scholar 

Download references


This project was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. The findings and conclusions in this Analysis have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.

Author information




K.M.T., C.N.C. and S.L.L. conceived and designed the project. S.R.D., M.K. and M.-L.C. conducted the analysis. K.M.T. and S.R.D. co-wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Katherine M. Tyner.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 314 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

D'Mello, S., Cruz, C., Chen, M. et al. The evolving landscape of drug products containing nanomaterials in the United States. Nature Nanotech 12, 523–529 (2017).

Download citation

Further reading


Find nanotechnology articles, nanomaterial data and patents all in one place. Visit Nano by Nature Research