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In the past few decades, researchers have identified biological pathways leading to neurodegenerative diseases and developed promising molecular agents to target them. However, the translation of these findings into clinically approved treatments has progressed at a much slower rate, in part because of the challenges scientists face in delivering therapeutics across the blood-brain barrier (BBB) and into the brain. To facilitate successful delivery of therapeutic agents to the brain, a team of bioengineers, physicians, and collaborators  created a nanoparticle platform, which can facilitate therapeutically effective delivery of encapsulated agents in mice with a physically breached or intact BBB. In a mouse model of traumatic brain injury (TBI), they observed that the delivery system showed three times more accumulation in brain than conventional methods of delivery and was therapeutically effective as well, which could open possibilities for the treatment of numerous neurological disorders. Findings were published in Science Advances.

Previously developed approaches for delivering therapeutics into the brain after TBI rely on the short window of time after a physical injury to the head, when the BBB is temporarily breached. However, after the BBB is repaired within a few weeks, physicians lack tools for effective drug delivery.

It's very difficult to get both small and large molecule therapeutic agents delivered across the BBB. The solution 's 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 technology could enable physicians to treat secondary injuries associated with TBI that can lead to Alzheimer's, Parkinson's, and other neurodegenerative diseases, which can develop during ensuing months and years once the BBB has healed.

The technology developed for this publication could allow for the delivery of large number of diverse drugs, including antibiotics, antineoplastic agents, and neuropeptides.

The therapeutic used in this study was a small interfering RNA (siRNA) molecule designed to inhibit the expression of the tau protein, which is believed to play a key role in neurodegeneration. 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, was used as the base material for nanoparticles. The researchers systematically engineered and studied the surface properties of the nanoparticles to maximize their penetration across the intact, undamaged BBB in healthy mice. This led to the identification of a unique nanoparticle design that maximized the transport of the encapsulated siRNA across the intact BBB and significantly improved the uptake by brain cells.

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

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.

BBB pathophysiology independent delivery of siRNA in traumatic brain injury, Science AdvancesDOI: 10.1126/sciadv.abd6889

https://medicalxpress.com/news/2021-01-nanoparticle-drug-delivery-b...

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