Trojan horse to transport drugs to brain
doi:10.1038/nindia.2016.38 Published online 21 March 2016
Delivering drugs to the brain – crossing the so-called blood brain barrier (BBB) – has always been a challenge. The BBB protects the functionality of the brain and central nervous system. Now, in what is claimed to be the first demonstration, Indian researchers have shown that nano carbon can easily cross the barrier – a discovery that has the potential to help Alzheimer, Parkinson or brain tumor patients1.
The researchers have shown the crossing of small-sized water soluble fluorescent carbon ‘nano onions’ (wsCNO) through the blood brain barrier in mice. One of the researchers Sabyasachi Sarkar at the Indian Institute of Engineering Science and Technology, Shibpur in West Bengal told Nature India that the wsCNO got readily excreted from the body after a few days suggesting their possible use as couriers for drug delivery to the brain.
Sarkar and co-workers created the carbon nano onions from cheap carbon sources like wood wool – a simple approach they had developed five years ago. ‘Oxidative treatment’, using nitric acid as the oxidizing agent, endowed them with photo luminescent properties and made them soluble in water. The researchers had earlier used the wsCNO thus created for in vivo imaging of the entire life cycle of the fruit fly (Drosophila melanogaster). They had also showed that this nano carbon can feed micro nutrients as well as water to young saplings even in arid zones "just like spoon feeding by mother.”
"Based on such usefulness of these nano onions, we decided to find out if they could also cross the BBB and reach the brain," Sarkar said.
To test this, the researchers developed a simple process to fragment the wsCNO and reduce their size. This consisted of nitric acid treatment in water bath followed by vacuum drying over solid sodium hydroxide. "Giving this treatment thrice, resulted in a crop of remarkably smaller fractions of nano onions less than 15 nm in size," Sarkar said.
In experiments spanning 6 to 8 months, old transgenic mice were induced with glioblastoma multiforme, a type of brain tumour, and CADASIL, a genetic disorder that contributes to vascular dementia in humans.
The experiment involved injecting the wsCNO in the tail of the mice and imaging their brain. "We observed the passage of wsCNO to the tumour and also to the neuronal sites," the researchers said. "The mice were then sacrificed and their brain slice were imaged by fluorescence microscopy to demonstrate the presence of wsCNO."
Interestingly the images of the brain of animals sacrificed after a wait period of three days showed no sign of nano carbons suggesting that the wsCNO do not accumulate in the brain of the animals but get released in their excreta.
"Thus we are delighted to report that wsCNO cross through the BBB and enter the brain without causing any perfusion," the report concludes. "This raises immense possibilities for drug delivery to the brain."
The researchers suggest that "at this stage it would be prudent to exploit the basic structure and different sizes of wsCNO which should carry and unload drug molecules of interest like a Trojan horse and can readily be removed from the site after the delivery."
1. Pakhira, B. et al. Carbon nano onions cross blood brain barrier. RSC Adv. (2016) doi: 10.1039/C5RA23534K