Nanotechnology in the biotechnology and pharmaceutical industries
Bionanotechnology is moving forward rapidly. It will enhance our understanding of biology and how biological systems work and is already helping resolve some of the pharma and biotech industries' significant problems. Dr Mike Fisher of the UK's Nanotechnology Knowledge Transfer Network (NanoKTN) gives an overview of its potential. October 2008
In 1959, American physicist Richard Feynman made a speech at CalTech, where he stated that ‘the principles of physics... do not speak against the possibility of manoeuvring things atom by atom’ when discussing his vision of ‘a billion tiny factories, which are manufacturing simultaneously’ . This is widely acknowledged as the first reference to nanotechnology.
Put simply nanotechnology is the technology of manipulating materials, devices, or systems at the nanometer scale. The term therefore does not apply to a particular industry sector, but can be applied across many. Nanotechnology can be applied to diverse areas from cosmetics to computing and from textiles to targeted drugs.
Currently the biotechnology and pharmaceuticals industries are facing pressures to decrease their expenditures as the total cost of getting a biologic drug to market has spiralled to over $1.2 billion, according to Tufts Centre for the Study of Drug Discovery . Companies are therefore looking to improve the discovery and development processes and gain more information about a new molecular entity (NME) to allow go/no go decisions to be made about a drug much earlier in the development stages.
Nanotechnology has started to come to the fore over the past few years as our knowledge and scientific capabilities have allowed manipulations at the nanolevel. Although, according to Frost & Sullivan only a small proportion (less than 5%) of global government’s research funding in nanotechnology has been applied to pharmaceuticals and healthcare, with the majority in chemicals and semiconductors.
That being said, there are numerous applications where nanotechnology is being applied to challenges within the biotech and pharmaceuticals industry, and in many cases industry is utilising technologies that fall into the nanotech definition, without them classifying the work as nanotech. This makes an accurate estimate of the extent of nanotechnology usage within the bio & pharma industry difficult to calculate.
A further issue is that this field is new and much of the work is blue-skies research and the applications being predicted are as good as people’s imaginations allow them to be. For example, will UC Berkley’s development of a bio-friendly nanowire light source lead to the development of cellular endoscopy? Possibly, but we are still far from achieving this. Distilling out areas where nanotechnology can make a practical difference for drug development companies now, can be difficult.
Driving the development
As healthcare improves, the world’s population is aging. The proportion of retirees in comparison to the economically active is growing. This is leading to increased downward pressure on spending in healthcare services. In addition, the cost of developing a drug is increasing. This is causing significant pressures within industry to gain savings wherever possible. The use of nanotechnology can help bring product discovery and development costs down by improving efficiency and decreasing the risk of product failure.
The major areas where nanotechnology can address problems in bio & pharma developments are listed and discussed below.
Nanotechnology has enhanced the drug discovery process, through miniaturization, automation, speed and reliability of assays. An additional benefit being seen is the decrease in the amounts of expensive reagents through integration of microfluidics with lab-on-a-chip systems.
Numerous systems have been developed over the past few years that apply micro and nanotechnology (MNT) to detect ligand interactions. For example, microcantilevers have been used as a label free way of directly measuring binding kinetics of drug candidates. Atomic Force Microscopy has also been demonstrated to have the ability to map ligand receptor binding on the surface of live cells. Here a functionalised AFM cantilever, combined with a confocal microscope is used to correlate images obtained by light microscopy with the presence or absence of receptor-ligand interaction. This can either reveal where functional receptors are present in correlation with an image of GFP-tagged receptors, or it can be used to examine the downstream reactions of a cell to topical application of just a few ligands.
Drug delivery & formulation
A significant challenge in drug development is delivering the drug to the right place in the body for it to be effective. The ideal situation would be to target a drug to the very cells that are diseased and to not affect those that are healthy. In practice, many systemically delivered drugs distribute throughout the body, often causing side effects. Often drugs can be potent in vitro, but ineffective in vivo due to an inability to reach the affected tissue or cells – for example crossing the blood brain barrier is a particular issue.
Nanotechnology can be applied to drug formulation and delivery systems in order to increase the delivery efficiency, or target certain tissues or cells. Nano carriers such as solid lipid particles, albumin, or polymer-based systems are being developed to aid drug delivery.
An example of a non-targeted nanocarrier is Abraxane (paclitaxel protein-bound particles for injectable suspension). The active ingredient, paclitaxel is a cancer chemotherapeutic originally delivered suspended in a non-ionic surfactant (Cremophor EL). This surfactant often leads to hypersensitivity reactions. By binding the drug to albumin nanoparticles, Abraxane demonstrated a doubling of the response rate (as compared to paclitaxel) in clinical trials and is approved by the FDA for sale in the US.
As technology advances, nanochips and nano arrays are becoming increasingly robust and accurate. By integrating these arrays with portable instruments capable of detecting ligand binding, etc on these chips, lab-on-a-chip systems can be produced, providing inexpensive point of care tests. Improvements in lateral flow, and robustness of the systems being created are allowing the development of diagnostic devices for use outside of specialist clinical biochemistry laboratories. The driving forces in the development of these systems are accuracy, speed and simplicity as diagnosis moves from centralised labs to the doctor’s surgery.
These systems have diverse applications, from cardiac risk assessment to bioterror agent detection, and hold promise for the use of stratified medicines, where genetic or other markers segment patients more likely to respond. Ultimately this will lead to supporting fully personalised medicine, delivered in the doctor’s clinic.
The application of nanotechnology in imaging is allowing greater resolution and accuracy. The technology is paving the way for the future of stratified medicine. Using imaging techniques, doctors may one day be able to tailor individual therapies to the very molecules that distinguish a patient's cancer from other cancer types. For example ‘quantum dots’ with proteins attached to the surface are being developed. These dots can bind to certain receptors on cells, for example in tumour cells. The quantum dots then allow high resolution imaging of exactly where these cells are in the body, allowing surgical removal and increasing the chances that tumour cells are not missed during the procedure and decreasing the chance of relapse.
The field of bionanotechnology is moving forward rapidly. There is no doubt that it will enhance our understanding of biology and how biological systems work. Nanotechnology is helping resolve some of the pharma and biotech industries' significant problems. It has already enabled new formulations for drugs that are commercially available, and there are a number of drugs in the R&D pipeline or that are in the regulatory approval stage.
In the future, nanotechnology will enhance the drug discovery process, through miniaturization, automation, speed and reliability of assays. It will also allow greater selection of the right drug for the right patient and enable the tests to support this decision process to be done in the doctor’s clinic.
Dr Mike Fisher, Theme Manager — Bionano & Nanomedicine, Nanotechnology Knowledge Transfer Network (NanoKTN).
1. Feynman, R. (1959) There’s Plenty of Room at the Bottom. Engineering & Science. February 1960.
2. Tufts CSDD Outlook 2008. http://csdd.tufts.edu/InfoServices/OutlookPDFs/Outlook2008.pdf Accessed 28 August 2008.
3. Safinia, L., (2008), Nanotechnology: Roadmap to Early Diagnosis of Disease. Frost & Sullivan. http://www.obbec.com/specialreports/134-nanotechnology/1999-nanotechnology-roadmap-to-early-diagnosis-of-disease/ Accessed 26 August 2008.
Further information on nanotechnology