Nanomedicine: opening very small doors

Nanomaterials offer significant advances for products where improvements are often incremental for performance or clinical benefit.
In materials performance, nanomaterials have the potential to offer faster, better and smaller devices.
Costs can be saved throughout the healthcare pathway, with earlier diagnosis, better disease management, fewer side effects and less invasive surgery.

Nanotechnology is starting to make an impact in the pharma space, particularly in drug delivery and diagnostics, but, as with other novel fields, there are challenges in getting regulatory approval for nanomaterials in medical applications. Pharmaphorum’s Linda Banks considers some of the ways that nanotechnology is advancing medicine and improving healthcare.

Nanomaterials are used in every field today, but healthcare is a particularly good target sector. These minute particles are bringing novel approaches to drug development and diagnostics, both for areas of unmet need and to reinvigorate existing therapies.

However, despite the many benefits, and patients’ positive response to advanced technologies, the numbers of approved products are still few and nanotechnology is yet to reach its full potential.

Let’s consider some of the advantages – and examine some of the barriers to more widespread uptake.

Applications in diagnostics and therapeutics

Nanomaterials offer significant advances for products where improvements are often incremental for performance or clinical benefit.

From a biological perspective, they can provide access through challenging biological barriers, such as the blood-brain barrier; they can also alter the characteristics of a therapeutic, resulting in reduced toxicity, increased solubility, or faster and longer biological action. Their extremely small size also enables them to interact at a DNA/RNA level.

Many therapeutics are large, complex molecules, which are slow to reach their target, or too fast or too slow to be metabolised or excreted. Nanotechnology can help improve the performance of these existing technologies. It promises faster time to clinic, longer life for patent-end products and new value for off-patent medicines.

In addition, from the perspective of materials performance, nanomaterials have the potential to offer faster, better and smaller devices.

Real-world examples

The positive, real-world impact of nanotechnology on health can be demonstrated by the following examples of existing therapies that have been improved with nanoparticles.

These include Paclitaxel, for breast, pancreas and lung cancer. This drug was insoluble in water and had several side effects. However, delivering Paclitaxel in a spherical nanoform (Abraxane) was found to resolve the solubility issue and significantly reduce the side effects of previous formulations.

Another chemotherapy, Doxorubicin, for breast, ovarian and bladder cancers, and leukaemia, often in combination, has been updated with pegylated liposomal delivery in the product Caelyx, whereby liposomes with nanostructures allow better delivery and can be tagged to be tumour-specific. This means better accumulation at the tumour and reduced cardio-toxic side effects.

In addition, the immunosuppressive agent for post-transplant organs, Sirolimus, has been given greater stability and improved bioavailability in the product Rapamune, which uses nanocrystal colloidal nanodispersion with reduced particle size.

Applications in the pipeline

So where are nanotechnologies most likely to drive innovation in healthcare in the future? Claire Skentelbery, director general of the Nanotechnology Industries Association (NIA), believes some of the most promising advances are likely to be seen in:

Contrast reagents for imaging
Materials for implants – making them smaller and more durable
Improved delivery of insulin and protection of pancreatic islets
Delivery to previously unreachable parts of the eye – and potential clinical impact in retinitis pigmentosa
Enhanced formulation of antibacterials to increase efficacy and reduce development of resistance, and
Tissue engineering – nano-porous scaffolds for biologic implants.

Case study – challenges and successes

While there are clear benefits in developing nanotechnologies for medical applications, the path to regulatory approval and use in patients is not always straightforward. What are the obstacles faced by companies working in the field?

In a webinar hosted by the NIA, the CEO of Endomag, Eric Mayes, explained the evolution of a nanotechnology to improve treatment in breast cancer.

The company saw an opportunity for its nanoparticle approach to better the current gold standard in the staging of nodes once cancer is confirmed. The leading approach up to 2010, sentinel lymph node biopsy (SLNB), used a radioisotope and blue dye injection. However, with a shortage of medical radioisotopes and processing capacity globally, the company’s plan was to replace the radioisotope-labelled colloid with a magnetic nanoparticle of similar dimensions and replace the gamma-ray detection probe with a magnetic probe to locate the magnetic nanoparticles taken by the sentinel lymph nodes.

The advantages of the magnetic nanoparticle are that it removes the need for a material with a half-life, improving availability and workflow, reduces radioactivity in the operating theatre and hospital waste stream, and provides the potential for a reliable and robust supply chain.

Challenges along the way included an early development crisis when iron oxide MRI contrast agents started disappearing from the market because of competition from gadolinium. This meant that the company had to develop something quickly. Its nanoparticle research suggested it needed to develop or source a sub-22nm iron oxide particle with a biocompatible coating that increased its diameter to ~60nm.

It ultimately sourced a material that had a long safety history as an MRI contrast agent – but MRI contrast agents are regulated as drugs.

However, Article 1(2)(a) of the Medical Device Directive 93/42/EEC (MDD) suggested that the product, Sienna, could be classed as a medical device as it achieved its primary intended action without employing pharmacological, immunological or metabolic means.

The company had to undertake a pre-clinical investigation to evaluate the mechanism of transport and retention in the lymph node, but in July 2011, the MHRA agreed that Sienna could proceed for evaluation as a Class IIa medical device.

A successful formulation, manufacturing and technical file audit supported CE approval in December of that year, making Sienna the first marketed nanoparticle medical device.

Endomag was spun out of University College London and the University of Houston in 2007. It launched the new platform in Europe in February 2013, expanding into the US market in mid-2016, and has treated more than 30,000 breast cancer patients in 30 countries to date.

Bright future

While regulatory and developmental hurdles remain, nanotechnology applications in healthcare look set to have a bright future. Costs can be saved throughout the healthcare pathway, with earlier diagnosis, better disease management, fewer side effects, less invasive surgery, fewer sick days, and less hospital time.

Also, many patent-end technologies can be reinvigorated without the full development costs of novel therapeutics. Further, nanomaterials can increase where interventions can take place, with diagnostics and treatments provided outside the hospital setting.

For human assessment, there are already processes in place and many existing nanomaterials could be applied in healthcare, so it is not about using novel materials in novel medicines.

Skentelbery recommends nanotechnology start-ups look at the regulatory requirements in the early development stages. In this field, the originators are rarely the ones who take innovative products to market, and there are many big pharma companies looking to help them navigate the regulatory pathway and post-marketing to bring promising treatments to patients.

Although there are many challenges, as Skentelbery concludes, “Nanotechnology is opening up a lot of very small doors.”

Linda Banks is managing editor of features and Deep Dive magazine at pharmaphorum. She has extensive experience as a journalist and editor, spanning business and consumer publications, and has specialised in the pharmaceutical and health sector since 2009.

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