In a first, the scientists have identified a new way to transport medication into the brain. According to the researchers, this could lead to improved treatments for neurological and neurodegenerative diseases.
The scientists, from Newcastle University, UK, have led an international team in a breakthrough in unlocking the secrets of how medications can infiltrate the brain. The study, published in the journal Nature Communications, noted that the new method allowed for combination drug delivery through intravenous injection to cross the blood-brain-barrier (BBB).
Blood capillaries in the brain are not permeable to many drugs and the majority are excluded from the brain by a protective barrier, called the blood-brain-barrier (BBB). The current treatment options are risky. Some viruses, however, have found ways to bypass the BBB and enter the brain. To treat certain neurological and neurodegenerative diseases, medication has to use modified viruses to bypass this barrier and deliver drugs to the area.
In the new research, scientists have has engineered small particles, similar to the size of viruses, from a peptide that can behave like a carrier to the brain and can be packed with drugs for intravenous injection. The study showed that: The filamentous bacteriophage fd bind a cell target with exquisite specificity through its few copies of display peptides, whereas nanoparticles functionalized with hundreds to thousands of synthetically generated phage display peptides exhibit variable and often-weak target binding.
It is hypothesised that some phage peptides in a hierarchical structure rather than in monomeric form recognize and bind their target. This study shows hierarchical forms of a brain-specific phage-derived peptide (herein as NanoLigand Carriers, NLCs) target cerebral endothelial cells through transferrin receptor and the receptor for advanced glycation end products, cross the blood-brain-barrier and reach neurons and microglial cells. Through intravenous delivery of NLC-β-secretase 1 (BACE1), siRNA complexes showed effective BACE1 down-regulation in the brain without toxicity and inflammation. Therefore, NLCs act as safe multifunctional nanocarriers, overcome efficacy and specificity limitations in active targeting with nanoparticles bearing phage display peptides or cell-penetrating peptides and expand the receptor repertoire of the displayed peptide.
Professor Moein Moghimi, who led the research, said: “Crossing the blood-brain-barrier has hindered the industry from effectively addressing central nervous system diseases, including brain tumours, and many neurological diseases like Parkinson’s, Alzheimer’s and Huntington’s.”
However, he added that some viruses have found ways to bypass the BBB and enter the brain. “We are very excited by our research – our delivery system is versatile and amenable to modifications, so, in principle, we can hopefully address shortfalls in drug delivery to the brain through intravenous injection,” said Moghimi.

Source: Science Daily, ET Healthworld, Independent.

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