Our Technology

Drug Delivery into the Brain

The brain is the most glucose hungry of our body’s organs, using up more than 20% of the glucose we ingest from food. To access this glucose, the most abundant transport protein in the blood brain barrier (BBB) is a specific type of glucose transporter known as Glucose Transporter 1 or GLUT1. To enable rapid absorption of glucose from the blood to the brain after a meal, GLUT1 is cycled between the brain and blood surfaces of the endothelial cells lining the BBB in response to changes in blood glucose.

By combining polymer nanoparticle packaging decorated with glucose ligands, and control of blood glucose levels to activate this cycling of GLUT1, Braizon’s technology conveys drugs across the BBB into the brain by a mechanism known as transcytosis.

Braizon’s nano-scale, safe, and biodegradable carriers extend circulation within the body and protect them from the drug removal mechanism of the BBB after transport into the brain. The process to package drugs within our carriers can be simple and not affect the pharmacological activity of the active compound. These carriers are engineered to fit their purpose and will release their cargo at the intended site. This occurs either in response to the local environment between the cells of the brain for extracellular release, or the reduced pH conditions within the endosomes of target cells for intracellular release.

Platform Capabilities

Braizon’s Drug Delivery System is highly versatile and offers the potential to deliver a wide range of therapeutic compounds, from small molecules to biologics, into the brain and spinal cord. Our glucosylated nanoparticles can enclose even high molecular weight or poorly stable molecules inside a protective polymer capsule. In cases where it may be necessary to optimize the structure of the carrier polymers to best fit the delivery needs of a therapeutic molecule, Braizon’s deep expertise in formulation can readily provide the most favorable solution.

Related papers

Therapeutic Molecule Article Summary
Antisense Oligonucleotides Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment Katsushima, Kataoka, et al. Nat Commun. 2016, 3616 Anti-sense Oligonucleotides targeting TUG1 coupled with a drug delivery system of cRGD peptide conjugated polymeric micelles
mRNA Modulated Protonation of Side Chain Aminoethylene Repeats in N-Substituted Polyaspartamides promotes mRNA Transfection Uchida, Kataoka, et al, J. Amer. Chem. Soc., 2014, 136, 12396-12405 Fine-tuning of chemical structure of polycation-based-carriers for safe and efficient mRNA transfection
Antibody Intracellular Delivery of Charge-Converted Monoclonal Antibodies by Combinatorial Design of Block/Homo Polyion Complex Micelles Kim, Kataoka et. al. Biomacromolecules, 2016, 17, 446–453 Polyion Complex (PIC) including Antibody micelles by optimization of charge-conversional degree
Small Molecule cRGD peptide-installed epirubicin-loaded polymeric micelles for effective targeted therapy against brain tumors Quader, Kataoka, et al, J. Control. Rel., 2017, 258, 56-66 Epirubicin (Anti-cancer drug) loaded micelles using Acetal-PEG- PBLA (poly benzal-aspartamide)

Publication

The following manuscript describes the basis of Braizon’s technology and was published by our scientific advisors in 2017.

Published by Springer Nature: Anraku, Y. et al. (2017) Glycaemic control boosts glucosylated nanocarrier crossing the BBB into the brain. Nature Communications 8: 1001-1009 Licensed under CC BY 4.0

Anraku. Y. et al. (2017) NUTURE COMMUNICATIONS 8: 1001-1009 SPRINGER NATURE