In an exciting new development, researchers have created a unique way to deliver TB medicines directly to the brain bypassing the challenging blood-brain barrier (BBB) that limits the effectiveness of many brain TB medicines. This innovative drug delivery method can effectively treat brain TB -- a life-threatening condition with high mortality rate.
Tuberculosis (TB) that affects the brain, called Central Nervous System Tuberculosis (CNS-TB), is one of the most dangerous forms of TB, often leading to severe complications or death. One of the biggest challenges in treating CNS-TB is that the drugs used to treat TB struggle to reach the brain because of a protective barrier known as the blood-brain barrier (BBB). This barrier prevents many medicines from entering the brain, limiting their effectiveness.
Traditional treatments involve high doses of oral anti-TB drugs, but these often fail to achieve effective concentrations in the cerebrospinal fluid due to the blood-brain barrier (BBB). This limitation underscored the need for more effective delivery methods that can target the brain directly.
Scientists at Institute of Nano Science and Technology (INST), Mohali, an autonomous institute of the Department of Science and Technology (DST) used tiny particles made of a natural material called chitosan, to deliver TB medicines directly to the brain through the nose, bypassing the BBB.
The scientists team led by Rahul Kumar Verma along with Krishna Jadhav, Agrim Jhilta, Raghuraj Singh, Eupa Ray, Vimal Kumar, Awadh Yadav and Amit Kumar Singh developed chitosan nano-aggregates, tiny clusters of nanoparticles made from chitosan, a biocompatible and biodegradable material. These tiny particles, known as nanoparticles, were then made into slightly larger clusters called nano-aggregates, designed for easy nasal delivery. They can hold TB drugs like isoniazid (INH) and rifampicin (RIF).
The drug delivery technology used was nose-to-brain (N2B) drug delivery, which utilizes the olfactory and trigeminal nerve pathways in the nasal cavity to bypass the BBB. By delivering the drug through the nasal route, the nano-aggregates can transport the drugs directly into the brain, significantly improving drug bioavailability at the infection site.
Besides, chitosan is known for its mucoadhesive properties, and sticks to the nasal mucosa, which helps the nano-aggregates stay in place and prolongs the time they can release the drug, enhancing its therapeutic effectiveness.
The spray-drying process used to form the nano-aggregates also ensures that they are stable, easy to administer intranasally, and can be efficiently absorbed into the brain tissues. This approach enables a much more targeted treatment of CNS-TB
When tested in the lab, these particles stuck well to the inside of the nose and were able to deliver much more medicine into the cells compared to regular TB drugs. When the new treatment was tested on mice infected with TB, the nasal delivery of these nano-aggregates reduced the number of bacteria in the brain by nearly 1,000 times more than in untreated mice.
This study is the first to show that delivering TB drugs through the nose using these advanced particles can effectively treat brain TB. The new treatment not only makes sure the medicine reaches the brain but also helps reduce the inflammation caused by the infection. This discovery published in the journal Nanoscale (Royal Society of Chemistry) has the potential to greatly improve treatment for people suffering from brain TB and could help in faster recovery.
It could be applied to treat other brain infections, neurodegenerative diseases (like Alzheimer’s and Parkinson’s), brain tumors, and epilepsy by enabling efficient drug delivery to the brain.
Publication link: https://doi.org/10.1039/d4nr02621g
