Neuro-inflammatory damage occurs when two types of brain cells called microglia and astrocytes normally deployed to protect the brain during infection and inflammation actually damage it by going into overdrive and destroying healthy brain cells along with damaged ones.
Directly treating cells in the brain has long proven difficult because of the biological and physiological systems that have evolved to protect the brain from blood-borne infections. The quest to deliver the drug to the brain also involved developing a technique to get past the brain-blood barrier, spare healthy brain cells and deliver the anti-inflammatory drug exclusively inside the rogue cells.
To do all this, the scientists used a globular, tree-like synthetic molecule, known as a dendrimer. Its size 2,000 times smaller than a red blood cell renders it fit for travel across the blood-brain barrier. Moreover, the dendrimer's tree-like structure allowed scientists to attach to it molecules of an anti-inflammatory NAC. The researchers tagged the drug-laced dendrimers with fluorescent tracers to monitor their journey to the brain and injected them into rabbits with cerebral palsy six hours after birth. Another group of newborn rabbits received an injection of NAC only.
Not only did the drug-loaded dendrimers make their way inside the brain but, once there, were rapidly swallowed by the overactive astrocytes and microglia.
"These rampant inflammatory cells, in effect, gobbled up their own poison," Kannan says.
"The dendrimers not only successfully crossed the blood-brain barrier but, perhaps more importantly, zeroed in on the very cells responsible for neuro-inflammation, releasing the therapeutic drug directly into them," says senior investigator Rangaramanujam Kannan, Ph.D., of the Center for Nanomedicine at the Johns Hop
|Contact: Ekaterina Pesheva|
Johns Hopkins Medical Institutions