by Pooja Shete on  January 4, 2021 at 1:32 PM Drug News
Novel Drug Delivery System Using Nanoparticles To Treat Brain Disorders
The researchers in the past few decades have identified various biological pathways leading to neurodegenerative diseases and have developed promising agents to target them. However, the translation of these findings into clinically approved treatments has progressed at a much slower rate. This is because the scientists have faced challenges to deliver therapies across the blood-brain barrier (BBB) and into the brain.

The blood brain barrier is a highly selective membrane that prevents solutes present in the blood from entering the brain.

The research conducted by a team of physicians, bioengineers, and collaborators at Brigham and Women's Hospital and Boston Children's Hospital is published in the journal Science Advances

To help in the successful delivery of therapeutic agents to the brain, the researchers created a nanoparticle platform, which can facilitate therapeutically effective delivery of encapsulated agents in mice with a physically damaged or intact BBB.

In a mouse model of traumatic brain injury (TBI), this delivery system showed three times more accumulation of the drug than the conventional methods of delivery and was also therapeutically more effective. These findings can open possibilities for the treatment of numerous neurological disorders.

The therapies which were developed previously to deliver drugs into the brain after TBI relied on the short window of time after a physical injury to the head, when the BBB is temporarily breached. However the physicians lacked tools for effective drug delivery after the BBB is repaired within a few weeks.

Corresponding author Nitin Joshi, PhD, an associate bioengineer at the Center for Nanomedicine in the Brigham's Department of Anesthesiology, Perioperative and Pain Medicine said, "It's very difficult to get both small and large molecule therapeutic agents delivered across the BBB. Our solution was to encapsulate therapeutic agents into biocompatible nanoparticles with precisely engineered surface properties that would enable their therapeutically effective transport into the brain, independent of the state of the BBB."

The nanoparticle drug delivery system will help physicians to treat secondary injuries associated with TBI that can lead to Alzheimer's, Parkinson's, and other neurodegenerative diseases, which can develop during months and years after the BBB has healed.

The BBB blocks the delivery of therapeutic agents to the central nervous system (CNS) for a wide range of acute and chronic diseases. This technology developed can allow the delivery of large number of drugs including antibiotics, antineoplastic agents, and neuropeptides.

For the study, a small interfering RNA (siRNA) molecule was designed to inhibit the expression of the tau protein, which plays a key role in neurodegeneration. The base material for nanoparticles was poly(lactic-co-glycolic acid), or PLGA, a biodegradable and biocompatible polymer used in several existing products approved by the U.S. Food and Drug Administration.

To maximize the penetration across the intact, undamaged BBB in healthy mice the researchers systematically engineered and studied the surface properties of the nanoparticles and identified a unique nanoparticle design that increased the transport of the encapsulated siRNA across the intact BBB and significantly improved the uptake by brain cells.

When mice with TBI received anti-tau siRNA through the novel delivery system, irrespective of the formulation being infused within or outside the temporary window of breached BBB, a 50 percent reduction in the expression of tau was observed. In comparison, those mice that received the siRNA through a conventional delivery system the tau protein was not affected.

First author of the study Wen Li, PhD, of the Department of Anesthesiology, Perioperative and Pain Medicine said, "In addition to demonstrating the utility of this novel platform for drug delivery into the brain, this report establishes for the first time that systematic modulation of surface chemistry and coating density can be leveraged to tune the penetration of nanoparticles across biological barriers with tight junction."

Along with targeting tau, the researchers also have studies underway to attack alternative targets using the novel delivery platform.

Karp said, "For clinical translation, we want to look beyond tau to validate that our system is amenable to other targets. We used the TBI model to explore and develop this technology, but essentially anyone studying a neurological disorder might find this work of benefit. We certainly have our work cut out, but I think this provides significant momentum for us to advance toward multiple therapeutic targets and be in the position to move ahead to human testing."

Source: Medindia

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