Copper Nanoclusters for Blood-Brain Barrier Penetration
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for Menkes syndrome, such as copper histidine complexes, fail to deliver copper to the brain, leading to unaddressed neurological symptoms and limited life expectancy and quality of life for affected children.
Innovation Solution
Development of copper nanoclusters with a mixed surface layer comprising histidine, acetate ions, and ascorbate ions, which are capable of passing through the blood-brain barrier, providing stable and bioavailable copper delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If copper histidine complex is administered parenterally, then copper is made available in the blood compartment, but copper cannot pass into the brain and neurological involvement is not treated
Solution Approach 1:
The patent changes the physical and chemical parameters of copper delivery by transitioning from copper histidine complex to copper nanoclusters with specific size (0.6-2.0 nm hydrodynamical diameter) and surface composition (histidine, acetate, and ascorbate ions). This parameter change enables the copper formulation to penetrate the blood-brain barrier while maintaining stability and bioavailability
Solution Approach 2:
The invention uses composite material structure where copper atoms are clustered and stabilized by multiple ligands (histidine, acetate ions, and ascorbate ions) on the nanocluster surface. This composite structure provides both the necessary stability for blood circulation and the capability to cross the blood-brain barrier, resolving the contradiction between blood availability and brain penetration
2Reliability
If current copper treatments are used, then copper levels in blood may be improved, but life expectancy and quality of life remain limited due to untreated neurological symptoms
Solution Approach 1:
The copper nanoclusters act as an intermediary carrier that facilitates copper transport across the blood-brain barrier. The nanocluster structure with specific surface ligands mediates the delivery of copper to the brain, enabling treatment of neurological symptoms and thereby extending life expectancy and improving quality of life
3Quantity of substance
If copper is administered to blood, then copper deficit in body is addressed, but neurological involvement persists due to inability to cross blood-brain barrier
Solution Approach 1:
The invention segments the copper delivery system into nanoscale clusters with specific size and surface properties, allowing differential distribution - copper is delivered to both blood and brain compartments simultaneously through the nanocluster formulation, thereby addressing both systemic and neurological copper deficits
Data Source
AI summary
Copper nanoclusters designated by the formula “CuNC@HisAc” or “CuNC@HisAcAsc”, wherein the copper nanoclusters: are covered on the surface thereof by a mixed layer including histidine (His), acetate ions (Ac) and possibly ascorbate ions (Asc); have a spherical shape; have a hydrodynamical diameter of 0.6-2.0 nm; have a metallic core with a diameter of 0.5-1.5 nm; have a temporal stability of 5-12 weeks in solution; have a temporal stability of at least 12 months in dried form; and have spectrophotometric properties, with a shoulder in the UV-Visible spectrum at 325±10 nm and a fluorescence spectrum with excitation wavelengths of 365-395 nm and emission wavelengths of 445-475 nm. Also, a method for preparation of the copper nanoclusters, and the use of the copper nanoclusters in a method treatment of pathologies related to a copper deficit, and in particular Menkes syndrome.