Ligand-Modified Copper Oxo-Hydroxide Nanoparticles
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Solution Overview
Problem
The development of effective delivery systems for antimicrobial copper ions remains an unresolved challenge, particularly for clinical use, as existing methods either result in biologically unavailable copper due to agglomeration or strong complexation, limiting their efficacy in treating wounds and infections.
Innovation Solution
Ligand-modified copper oxo-hydroxide nanoparticles with a high surface area-to-volume ratio and enhanced reactivity are developed, allowing for efficient release of free copper ions by non-stoichiometric substitution of oxo or hydroxy groups with carboxylic acid ligands, such as tartarate and adipate, enhancing their antibacterial properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If copper ions are delivered using conventional methods, then copper is provided in the formulation, but copper becomes biologically unavailable due to agglomeration or strong complexation
Solution Approach 1:
The invention uses a composite material system consisting of copper oxo-hydroxide core particles modified with carboxylic acid ligands (such as tartarate and adipate). This composite structure allows the copper to remain in a labile, biologically available form while preventing agglomeration through ligand stabilization and avoiding strong complexation that would reduce bioavailability. The ligand-modified surface provides controlled release of free copper ions.
Solution Approach 2:
The invention changes the chemical parameters of copper delivery by using ligand-modified copper oxo-hydroxide nanoparticles with specific carboxylic acid ligands. This modifies the dissolution behavior and copper release characteristics, maintaining free copper ion availability while preventing the harmful effects of agglomeration and strong complexation. The non-stoichiometric substitution of oxo or hydroxy groups with ligands creates optimal conditions for copper release.
2Reliability
If silver is used for antimicrobial treatment, then greater antimicrobial efficacy is achieved, but cost, in vivo toxicity and chemical instability increase
Solution Approach 1:
The invention replaces expensive silver with copper, which is inexpensive and can be used at greater doses. The copper oxo-hydroxide nanoparticles are designed to release free copper ions that provide antimicrobial activity. The ligand modification ensures the copper remains stable in formulation but releases actively when needed, providing a cost-effective alternative to silver.
Solution Approach 2:
The invention changes the metal parameter from silver to copper, and modifies the copper delivery system using ligand-modified oxo-hydroxide nanoparticles. This parameter change reduces cost and toxicity while maintaining antimicrobial efficacy through controlled release of free copper ions, avoiding the chemical instability issues of silver.
3Object-generated harmful factors
If copper is used for antimicrobial treatment, then cost is reduced and in vivo tolerance is improved, but biocidal efficacy decreases
Solution Approach 1:
The invention changes the physical parameters of copper delivery by using nanoparticles with high surface area-to-volume ratio and ligand modification. This increases the dissolution rate and bioavailability of free copper ions, enhancing biocidal efficacy while maintaining the cost and tolerance advantages of copper over silver.
Solution Approach 2:
The ligand-modified copper oxo-hydroxide composite provides enhanced biocidal efficacy through controlled release of free copper ions. The carboxylic acid ligands modify the copper release kinetics, ensuring sufficient bioavailability for antimicrobial activity while maintaining copper's inherent advantages of low cost and good in vivo tolerance.
4Stability of the object's composition
If ligands are stoichiometrically substituted for oxo or hydroxy groups, then structured complexes are formed, but dissolution and bioavailability of free copper ions are reduced
Solution Approach 1:
The invention changes the substitution parameter from stoichiometric to non-stoichiometric ligand substitution. This creates a balance where enough ligands are present to stabilize the nanoparticle structure and prevent agglomeration, but not so many that they block copper dissolution and release. The non-stoichiometric substitution optimizes both structural stability and copper bioavailability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The ligand-modified copper oxo-hydroxide nanoparticles demonstrate superior antibacterial activity compared to commercial copper oxide and silicate-stabilized copper hydroxide nanoparticles, achieving significant bacterial growth inhibition and maintaining lability upon resuspension, making them suitable for clinical applications.
Implementation Method 1
the copper oxo-hydroxide nanoparticles have a structure in which the one or more ligands are non-stoichiometrically substituted for the oxo or hydroxy groups
Implementation Method 2
the inclusion of the ligands helps to modulate the dissolution of the nanoparticles to provide free soluble copper ions
Implementation Method 3
capable of delivering biocidal concentrations of copper, typically in the form of free copper ions (Cu2+)
Data Source
Figure 1
Figure 2A~2D
Figure 3A~3D
AI summary
Antibacterial compositions comprising nanoparticles formed from copper oxo-hydroxide are described that are capable of delivering biocidal concentrations of copper, typically in the form of free copper ions (Cu2+). The nanoparticle compositions generally comprise small particles, typically having mean diameters in the range of 1-100nm, having comparatively high surface area-to-volume ratio and enhanced reactivity compared to the corresponding bulk counterpart materials and which are sufficiently labile to release the free copper efficiently.