From Chemistry & Industry News, September 2015

C_I

‘THE ANNOUNCEMENT OF BENIGN, NON- TOXIC NANOTUBES IS SIGNIFICANT AND EXCITING'
Andrei Khlobystov director, University of Nottingham’s Nanotechnology & Nanoscience Centre

MEDICAL GRADE NANOTUBES
Cath O’Driscoll

After years of searching, researchers say they have come up with a scalable process to make ‘the world’s first medical grade carbon nanotube’.

Not only are the new Medical Grade Molecular Rebar (MGMR) nanotubes safe and non-toxic, according to researchers at Cambridge, MA-based company BioPact, which exhibited the technology at the ACS meeting in Boston in August 2015, but crucially they can also be made in quantities of several tonnes/ year– up to commercial-scale as needed.

‘Ever since they were discovered in 1991, people have spent billions trying to get a scalable technology to make discrete, clean, consistent batches of carbon nanotubes,’ said Herschel Watkins, lead scientist at BioPact. ‘Now we have solved that problem.’

Carbon nanotubes (CNTs) hold tremendous potential in medicine because of their high aspect ratio: their relatively long length and small width means they have an extremely high surface area that allows them to enter cells and cross the blood- brain barrier into the brain. To date, however, applications have been limited because of safety concerns.

Current manufacturing processes for CNTs leave behind traces of heavy and sometimes toxic metals such as cadmium, lead and alumina, which can leach out and poison the host, Watkins elaborated. They also frequently result in a ‘knotted amorphous mass’ of tubes, ranging from a few microns to tens of microns long, that have lost their needle-like shape and are associated with asbestos-like carcinogenicity problems seen in animal studies.

‘Getting the metals out has until now been an expensive and not really scalable process,’ Watkins said. ‘People have made short tubes without metals before but only at a small scale in laboratories, so to get a few mg would take a week or more. One reason we are so different is because our process is scalable.’

The new manufacturing process to make MGMR nanotubes was invented by a group of former-Dow Chemical company scientists who set up a separate, partner company to BioPact to develop the tube and explore other non-medical and energy-related applications.

Details of the process remain under wraps; however, Watkins notes that it results in consistent batches of clean, open-ended nanotubes all less than a single micron in length ready for targeted drug delivery applications.

‘The higher the aspect ratio, the more surface area relative to the smallest dimension but if the tubes are too long they can raise toxicity concerns,’ he said: ‘Tubes from 10–15nm across by 800–900nm long are the optimal dimension to create a safe high surface area particle while maintaining a narrow cross section.’

Unpublished studies in mice have shown that MGMR tubes are safe and free from side effects even at doses up to 3mg, Watkins notes – equivalent to a 12g dose in humans. Mice given one of the ‘best commercially available’ CNTs, in contrast, all died after the first dose, Watkins says, ‘whereas all our mice survived the entire experiment with no effects.’

Four R&D kits containing the MGMR tubes are now being made available for exploratory studies.

‘The announcement of biologically benign, non-toxic carbon nanotubes is significant and exciting,’ commented Andrei Khlobystov, director of the University of Nottingham’s Nanotechnology & Nanoscience Centre. ‘This opens up a huge potential avenue for nanotube applications in medicine, from cancer therapy, to transdermal drug delivery, to new treatments for neurodegenerative diseases. The sub-micrometre length of the BioPact nanotubes and their surface functionality compatible with biological systems must play roles as important as the nanotubes purity for minimising their toxicity.’

However, to harness the full potential of the MGMR tubes for drug delivery and other therapeutic applications, Khlobystov added that ‘the fundamental physical chemistry of drug molecules encapsulation and release needs to be fully explored and understood. The nanotube-molecule interactions are highly complex and unpredictable, and require careful spectroscopy and microscopy analysis at each stage, so I will be eagerly watching development of this new nanomaterial towards real-life applications.’

The process to make MGMR tubes will be ‘significantly less than for other methods to make clean CNTs,’ Watkins said; they will add very little to the overall cost of an approved drug.