Researchers have developed a new method to deliver Tuberculosis (TB) medicines directly to the brain, bypassing the blood-brain barrier (BBB), a protective barrier that limits the effectiveness of traditional treatments for brain TB. This method, designed to treat Central Nervous System Tuberculosis (CNS-TB), has the potential to significantly improve outcomes for this life-threatening condition.
CNS-TB is one of the most dangerous forms of tuberculosis, often leading to severe complications or death. The biggest challenge in treating CNS-TB is the BBB, which prevents many medicines from reaching the brain. Traditional treatments involve high doses of oral anti-TB drugs, but these fail to achieve effective concentrations in the cerebrospinal fluid, making the need for an alternative delivery method critical.
A team of scientists at the Institute of Nano Science and Technology (INST), Mohali, led by Rahul Kumar Verma, has developed a novel approach using chitosan, a natural, biocompatible, and biodegradable material. The team, including Krishna Jadhav, Agrim Jhilta, Raghuraj Singh, Eupa Ray, Vimal Kumar, Awadh Yadav, and Amit Kumar Singh, created chitosan nano-aggregates to deliver TB drugs directly to the brain through the nasal cavity.
The researchers developed nanoparticles made from chitosan, which were then clustered into larger nano-aggregates. These aggregates are designed for nasal delivery and can carry common TB drugs such as isoniazid (INH) and rifampicin (RIF). This delivery system, known as nose-to-brain (N2B) drug delivery, uses the olfactory and trigeminal nerve pathways to bypass the BBB. Delivering the drugs through the nasal route significantly improves their bioavailability at the infection site in the brain.
Chitosan’s mucoadhesive properties allow the nano-aggregates to adhere to the nasal mucosa, prolonging the release time of the drugs and enhancing their therapeutic effectiveness. The use of a spray-drying process ensures that the nano-aggregates are stable and easy to administer intranasally, while also enabling efficient absorption into brain tissues.
Laboratory tests demonstrated that these particles adhered well inside the nasal cavity and delivered a higher concentration of medicine to brain cells compared to regular TB drugs. In tests on mice infected with TB, nasal delivery of the nano-aggregates reduced the bacterial load in the brain by nearly 1,000 times compared to untreated mice.
This study, published in the journal Nanoscale, is the first to demonstrate that delivering TB drugs through the nose using advanced particles can effectively treat brain TB. The treatment also reduces the inflammation caused by the infection, offering a more targeted and effective approach to combating CNS-TB.
In addition to treating TB, this technology could potentially be applied to other brain infections, neurodegenerative diseases such as Alzheimer’s and Parkinson’s, brain tumours, and epilepsy, by enabling efficient drug delivery to the brain.