Nanoparticles as small as ca. 35 nm have entered clinic testing, demonstrating minimised non-target extraction by the kidney and liver/spleen, which translates to an enhanced therapeutic window with low variations in systemic peak. These intentional changes in the pharmacokinetics/pharmacodynamics of the active drug may alter the pharmacology. For instance, a Phase I oncology study of a cyclodextrin-camptothecin nanoparticle (ca. 38 nm) developed at the California Institute of Technology (USA) demonstrated long-term stabilisation of tumours with repeated low doses, but was unable to generate partial responses at the maximum tolerated dose.1 Therefore, the ability to modify the pharmacology or tolerability of specific drug classes could be a great benefit.
Nanotechnology is enabling new applications in the areas of molecular imaging and early detection, in vivo imaging, reporters of efficacy, multifunctional therapeutics and research tools. Significant advances have been made in all of these areas thanks to the funding awarded in 2004 by the US National Cancer Institute's (NCI) Alliance for Nanotechnology, which funded eight Centers of Cancer Nanotechnology Excellence and 12 Cancer Nanotechnology Platform Partnerships.
From a research perspective, the programme has already yielded more than 1000 peer-reviewed journal publications. From a clinical translation perspective, 50 diagnostics and therapeutic companies have collaborated with this programme and 34 new companies have been formed in the last 4 years — 10 of these new companies were formed just last year. Combined, they have a strong intellectual property portfolio of more than 200 disclosures and patents filed. Additionally, 8–10 clinical trials are associated with this programme and several companies are in pre-IND discussions with the FDA.
Drug delivery is another hot area where nanotechnology has made significant contributions. Today's drugs have issues such as systemic and non-specific delivery, side effects and the need for organic solvents. With nanotechnology, however, advances have been made towards improved localised delivery of drugs to tumour sites, improved efficacy and reduced side effects. Several nanotech-enabled drugs can now be found on the market such as Abraxane (Abraxis BioSciences), an albumin-bound paclitaxel for metastatic breast cancer; liposomal therapies Doxil, DaunoXome and Myocetp; and polymeric therapies, which include Genexol-PM and Oncaspar.
Outside of the NCI Alliance programme, nanotechnology has played a part in addressing an estimated 40%+ of compounds that have poor solubility, which results in reduced efficacy and also makes them difficult to develop. Elan has led the way with its acquisition of NanoCrystal Technology; the key benefits of the technology include, among others, improved biocompatibility, increased absorption rate, dose reduction, faster formulation of compounds, increased performance through variable administration routes (excluding injectable and inhalant delivery methods). Elan had its fifth product approved in late 2009 and has also licensed this technology to J&J, AstraZeneca, Roche and Bristol-Myers Squibb, to name a few.
Elsewhere, significant advances have also been made in diagnostics, through the identification of specific disease biomarkers and non-invasive imaging.
The current impact for the pharma industry has been modest; probably more than $2 billion annually in sales. It is unrealistic to expect much more in the short term, given the corresponding slow introduction of biologicals onto the market from the lab. This subject is addressed further by the European Technology Platform in their roadmap.2