New Drug Delivery Method Bypasses Blood-Brain Barrier to Effectively Treat Brain TB

CNS-TB poses significant treatment challenges, as the BBB—a protective shield around the brain—prevents many drugs from reaching effective concentrations in the brain.

In a groundbreaking development, researchers have unveiled a revolutionary method to deliver tuberculosis (TB) medicines directly to the brain, bypassing the challenging blood-brain barrier (BBB). This advancement, led by scientists at the Institute of Nano Science and Technology (INST) in Mohali, has the potential to dramatically improve treatment outcomes for patients suffering from Central Nervous System Tuberculosis (CNS-TB), a severe and often fatal form of TB.

CNS-TB poses significant treatment challenges, as the BBB—a protective shield around the brain—prevents many drugs from reaching effective concentrations in the brain. Traditional TB treatments, administered orally, struggle to penetrate this barrier, often resulting in limited success against brain TB infections. This hurdle has made CNS-TB one of the deadliest forms of tuberculosis, with high mortality rates.

The research team, led by Rahul Kumar Verma and supported by colleagues Krishna Jadhav, Agrim Jhilta, Raghuraj Singh, Eupa Ray, Vimal Kumar, Awadh Yadav, and Amit Kumar Singh, developed a novel drug delivery system using chitosan nano-aggregates. These nanoparticles are clusters of tiny, biocompatible particles made from chitosan, a natural material known for its safety and biodegradability. The nano-aggregates were designed for easy nasal delivery, enabling the direct transport of TB drugs, such as isoniazid (INH) and rifampicin (RIF), to the brain by bypassing the BBB.

The innovative technique called nose-to-brain (N2B) drug delivery, takes advantage of the olfactory and trigeminal nerve pathways in the nasal cavity to bypass the BBB. This method significantly increases the bioavailability of the drugs in the brain, leading to a more effective and targeted treatment for CNS-TB.

One of the key benefits of chitosan is its mucoadhesive properties, which allow the nano-aggregates to stick to the nasal mucosa, prolonging the release of the drug and enhancing its therapeutic effect. The nano-aggregates are produced through a spray-drying process, making them stable, easy to administer, and highly absorbable in brain tissues.

When tested in laboratory settings, this approach demonstrated remarkable results. The nano-aggregates were able to deliver significantly more medicine into brain cells compared to traditional methods. In animal studies involving mice infected with TB, the nasal delivery of these nano-aggregates reduced the bacterial count in the brain by nearly 1,000 times compared to untreated mice.

This innovative treatment method not only ensures that the TB drugs reach the brain but also helps reduce the inflammation caused by the infection. The research, published in the journal Nanoscale (Royal Society of Chemistry), marks the first instance of successfully using nano-aggregates for TB drug delivery via the nasal route. The findings could greatly improve the treatment of CNS-TB in humans, offering a faster and more effective recovery.

Beyond TB, this method has broader potential applications. It could be adapted to treat other brain infections, as well as neurodegenerative diseases such as Alzheimer’s and Parkinson’s, brain tumors, and epilepsy, by providing a more efficient way to deliver drugs directly to the brain. This discovery represents a major step forward in the field of neurological drug delivery and brain disease treatment.