Nanomedicine in the clinic

The rate of advancement of nanomedicine in the clinic is highly dependent on the intended application.  Diagnostic devices, especially devices that will not be used in vivo, face fewer hurdles than therapeutics, which are typically introduced directly into the body.  Nevertheless, there are many nanomedicine products that have moved past the basic research phase and are now progressing through clinical trials or even been approved for commercial use in the clinic.

In 2013, a review article written by McCullough and coworkers noted that there were 247 nanomedicine products approved for, or already in, clinical studies and an additional 100 commercially available products.[1] Liposome nanostructures* accounted for the largest number of nanomedicines clinical studies, with polymeric nanoparticles and emulsions ranking second and third, respectively.  All three of these nanostructures tend to be used to enhance delivery of already approved medicines to cells of interest, most likely tumour cells as cancer treatment accounted for the vast majority of applications.

Liposome loaded with therapeutic drug

*Liposomes are self-assembled hollow spheres made up of molecules with hydrophilic heads and hydrophobic tails. The outside and inside surfaces of the sphere are hydrophilic while the wall of the sphere is hydrophobic. This structure, with both environments present, allows for the delivery of water soluble and/or water insoluble drugs. In addition, the inner regions protect drugs from premature degradation while being transported through the body, while the outer surface can be functionalised so that the liposome will preferentially interact with, for example, cancer cells.

Protein nanoparticles are another important form of nanomedicine used in the clinic.[2] Paclitaxel, for example, is a well-established chemotherapy agent that is poorly soluble in water, which makes delivering it to tumors at an effect concentration very challenging. By conjugating paclitaxel to a carrier protein, which is then formulated into a protein nanoparticle dispersion, makes it effectively more soluble in the bloodstream and better absorbed into tumor cells, resulting in greater antitumor activity. Similarly, polymer-drug conjugates are formed by linking active medicines to polymers to enhance solubility, stability and/or delivery.

Several nanomedicine formulations have been approved for treatment of diseases, particularly cancers.  The first nanomedicine drug to be approved for use in the clinic was Doxil (also known as liposomal doxorubicin), approved by the US FDA in 1995.[3]  It is a liposome formulation with the drug carried in the hydrophobic layer of liposome particles that are ~100 nm in diameter (about the size of a virus). The paclitaxel/carrier protein formulation mentioned above is known as Abraxane (developed by Abraxis corporation), approved by the US FDA in 2005.

Many other nanomedicine formulations have been approved for the treatment of not only various cancers, but also meningitis, fungal infections and macular degeneration, among others.[4-6] With the number of nanomedicines in clinical trials continuing to increase, the potential for improved treatment of diseases is only just beginning to be realised.

 

[1] Etheridge, M. L., Campbell, S. A., Erdman, A. G., Haynes, C. L., Wolf, S. M., and McCullough, J. (2013) The big picture on nanomedicine: the state of investigational and approved nanomedicine products, Nanomedicine 9, 1-14.

[2] Min, Y., Caster, J. M., Eblan, M. J., and Wang, A. Z. (2015) Clinical Translation of Nanomedicine, Chemical Reviews.

[3] Barenholz, Y. (2012) Doxil® — The first FDA-approved nano-drug: Lessons learned, Journal of Controlled Release 160, 117-134.

[4] Tinkle, S., McNeil, S. E., Mühlebach, S., Bawa, R., Borchard, G., Barenholz, Y., Tamarkin, L., and Desai, N. (2014) Nanomedicines: addressing the scientific and regulatory gap, Annals of the New York Academy of Sciences 1313, 35-56.

[5] Pillai, G. (2014) Nanomedicines for Cancer Therapy: An Update of FDA Approved and Those under Various Stages of Development, SOJ Pharmacy & Pharmaceutical Sciences, 1(2), 13.

[6] Ventola, C. L. (2012) The Nanomedicine Revolution: Part 2: Current and Future Clinical Applications, Pharmacy and Therapeutics 37, 582-591.