Therapeutic Drugs and the Blood Brain Barrier: How to Break on Through to the Other Side

 We have all seen the headlines on traumatic brain injuries (TBI) and litigation – they run the gamut from sports injuries to motor vehicle accidents. What we don’t hear about is one of the biggest obstacles in treating brain injuries or disorders: the difficulty in delivering therapeutics across the blood brain barrier (BBB).  Most drugs do not contain the appropriate chemical properties allowing them to cross the BBB. The need for safe drug delivery technologies that can permeate the BBB and effectively target involved areas is a driving force in the market.

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Current research is exploring the implementation of biotechnology to assist drugs in crossing the BBB. One potential approach uses nanoparticles (particles ≤ nm) to encapsulate therapeutic drugs. This approach offers advantages due to non-invasiveness, targeting efficiencies, biodegradability, and stability to release drugs. 

Researchers at Brigham and Women’s Hospital and Boston Children’s Hospital have studied a particular polymer-based nanoparticle used to deliver a therapeutic across the BBB in TBI. TBI can lead to long-lasting secondary injuries, such as neurological and cognitive deficits, behavioral changes and gait abnormalities and neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease.  The researchers employed a therapy based on small interfering RNA (siRNA), a short sequence of RNA that silences gene expression, designed in this study to silence the expression of a microtubule-associated protein called tau. Although tau is normally involved in the stabilization of microtubules for healthy cell growth, abnormal buildup of this protein has been implicated in various neurodegenerative diseases including Alzheimer’s disease. In order to develop a therapeutic that can cross the BBB, the scientists encapsulated the siRNA in nanoparticles consisting of polylactide-co-glycolide (PLGA), a biodegradable and biocompatible polymer. Using a mouse model, Li et al. demonstrated a threefold higher brain accumulation of the nanoparticles and 50% reduction of tau expression, indicating delivery of the siRNA was therapeutically effective in crossing the BBB and silencing tau in TBI mice.

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Currently, the FDA has approved PLGA for approximately 20 drugs to treat various illnesses, including cancer, diabetes, and mood disorders. However, the FDA has not approved a PLGA drug delivery device for the treatment of TBI or neurodegenerative diseases. In fact, the FDA has not approved any new therapeutics for treating Alzheimer’s disease since 2003. Li et al. suggest that, based on the efficacy of their novel drug delivery system, doors could open up for the possibility of treating other neurological disorders in a similar manner. Jeffery Karp, a co-author of the paper, stated: “‘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.’"

While still in the pre-clinical stages of testing, this new drug delivery device offers future hope for the pharmaceutical community, as we work toward effectively treating brain injuries and disorders.