Science Sub-Paper: Develop nanoparticles that can cross the blood-brain barrier!

Over the past few decades, scientists have identified biological pathways that cause neurodegenerative diseases and developed promising molecular agents for these pathways.
, however, the pace of translating these findings into clinically approved treatments has been much slower, in part because of the challenges faced in passing therapeutic drugs through the blood-brain barrier (blood-brain barrier, BBB) and into the brain.
In a new study, researchers from Bregan Women's Hospital and Boston Children's Hospital in the United States have built a nanoparticle platform that promotes the effective delivery of encapsulated drugs to physically destroyed or complete BBB in mice.
in a mouse model of traumatic brain injury (TBI), they observed that the delivery system accumulated three times as much in the brain as traditional delivery methods, and that the treatment worked well, which may have made it possible to treat many neurological disorders.
the study was published in the Journal of Science Advances on January 1, 2021 under the title "BBB pathophysiosiology-independent delivery of siRNAinrac brain injury".
previously developed method of delivering therapeutic drugs to the brain after TBI occurs depends on a short window of time after physical head injury, at which point BBB is temporarily destroyed.
, however, doctors lacked effective drug delivery tools after the damaged BBB was repaired within weeks.
Nitin Joshi, an assistant bioengineer at the Nanomedical Center in the Department of Anesthesiology, Peri surgery and Pain Medicine at Bregan Women's Hospital and co-author of the paper, said, "It's very difficult for both large and small molecule therapists to get through BBB.
our solution is to encapsulate therapeutic agents into biocompaturable nanoparticles with precisely engineered surface properties, so that they are effectively delivered to the brain therapeuticly, independent of the state of BBB.
" technology allows doctors to treat secondary TBI-related injuries that can lead to Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases that can occur months and years after BBB heals.
Dr. Jeff Karp, co-author of the paper and in the Department of Anesthesiology, Peri surgery and Pain Medicine at Bregan Women's Hospital, said, "This has been, to some extent, the highest goal in the field in order to be able to pass through BBB delivery agents without inflammation."
our extremely simple approach to many neurological disorders, in which therapeutic drugs are expected to be delivered to the brain. Dr. Rebekah Mannix of the Department of Emergency Medicine at Boston Children's Hospital, co-author of the
paper, further emphasized that BBB prevents the delivery of therapeutic drugs to the central nervous system (CNS) for the treatment of a variety of acute and chronic diseases.
, "The technology developed in this paper enables the delivery of a wide range of different drugs, including antibiotics, anti-tumor drugs and neuropeptides."
this could lead to changes in the treatment of many diseases that occur in the central nervous system.
the drug used in the study was a small interfering RNA (siRNA) molecule designed to inhibit the expression of the tau protein, which is thought to play a key role in neurodegeneration.
Polyctic-cohydroxyacetic acid, or PLGA, is a biodegradable and biocompasitive polymer used as a base material for nanoparticles in several existing products approved by the U.S. Food and Drug Administration (FDA).
the researchers systematically designed and studied the surface properties of the nanoparticles to maximize their complete, undestructed BBB penetration in healthy mice.
this led to the development of a unique nanoparticle design that maximized the delivery of encapsulated siRNA in complete BBB and significantly improved brain cell absorption.
In TBI mice that sent tau-inhibiting tau protein through this new delivery system, tau expression was observed to be reduced by 50 percent, regardless of whether the therapeutic agent was delivered within or beyond the short window of the destroyed BBB.
, tau was not affected in mice that sent siRNA through traditional delivery systems. "In addition to demonstrating the usefulness of this new platform in delivering drugs to the brain, this paper is also the first systematic adjustment of surface chemical properties and coating densities to adjust the ability of nanoparticles to pass through tightly connected biological barriers," said Dr. Wen Li of the Department of Anesthesiology, Peri surgery and Pain Medicine at Bregan Women's Hospital, the lead author of the
paper.
in addition to targeting tau, the researchers are also studying the use of this new delivery platform to attack other targets.
, "For clinical transformation, we want to go beyond tau to verify that our system can adapt to other targets."
we use TBI models to explore and develop this technology, but basically anyone who studies neurological disorders may find the benefits of this study.
our research is tough, but I think it gives us an important impetus to advance to multiple therapeutic targets and has the potential to advance to human testing.
" Reference: 1. Wen Li et al. BBB pathophysiology–independent delivery of siRNA in traumatic brain injury. Science Advances, 2021, doi:10.1126/sciadv.abd6889.2.Nanoparticle drug-delivery system developed to treat brain disorders This article is from Bio Valley, for more information please download Bio Valley APP (