Drug delivery
An illustration of the components
that make up the blood- brain barrier.
reduce the rate at which the body clears the peptide from the blood. “Another important aspect for trans-blood-brain-barrier delivery is the prerequisite to maximise transcytosis – meaning that peptide shuttles need to avoid the endosomal/ lysosomal degradation pathway that would reduce the amount that effectively reaches the brain,” says Neves. “Finally, apart from the strong evidence that peptide shuttles dramatically improve brain delivery – the amount reaching the brain remains low. In the end, it is important to evaluate the efficacy of the payload to effectively assess that the amount ‘delivered’ is enough for treatment.”
“In the end, it is important to evaluate the efficacy of the payload to effectively assess that the amount ‘delivered’ is enough for treatment.”
Vera Neves, senior staff researcher at the University of Lisbon
The future of drug delivery While the effects of peptide shuttles to bypass the blood-brain barrier are yet to be tested on humans, studies have shown promising results in animal models of brain diseases, including Alzheimer’s disease and glioblastoma. Peptide shuttles have been intensively investigated for the delivery of different drugs, some examples being: chemotherapeutics for the treatment of brain cancer (glioma), such as Paclitaxel, Doxorubicin, Temozolomide; and the biologics like peptise,
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proteins and antibodies, for the treatment of cerebral Ischemia, Parkinson’s, Alzheimer’s, Hunter Syndrome and other brain diseases, explains Neves.
Among a handful of companies who are on the cutting edge of developing this technology is Denali Therapeutics, whose large molecule transport vehicle (TV) platform technology uses an engineered Fc fragment that exploits receptor- mediated transcytosis for CNS delivery of biotherapeutics. Denali Therapeutics is one of many pharmaceutical companies who believe that the development of the peptide shuttle will play a critical role in enabling effective neurological treatments.
Despite the development of peptide shuttles and other strategies to delivery therapeutic agencies across the blood-brain barrier being a promising area of research, there is still the risk of an immune response. Many of these peptides can induce an immune response and cause toxicity, which has the potential to increase the risk of adverse side effects. As well as this, the pharmacokinetics of blood-brain-barrier-targeting peptides can pose a challenge due to their short half-life, which can limit their overall effectiveness. These are all areas for which researchers will need to find a solution before they can move peptide shuttles towards first-in-human trials with therapeutics. Currently, there are over 150 peptides in the process of being developed for clinical development. Evidently, the field of peptide shuttles for neurological diseases is rapidly evolving and the potential for it is vast. ●
World Pharmaceutical Frontiers /
www.worldpharmaceuticals.net
Olha Pohrebnyak/
www.shutterstock.com
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