Stable Titanium Vanadium Complexes Nanoparticle Delivery

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Solution Overview

Problem

Titanium (IV) based anticancer complexes face limitations due to aquatic instability and the need for hydrolysis, which affects their cytotoxicity and stability, while vanadium complexes show high cytotoxicity but low stability in water, hindering their effectiveness.

Innovation Solution

Development of highly water-stable titanium complexes without labile ligands, which are formulated into nanoparticles to enhance solubility and cell penetration, eliminating the need for hydrolysis and reducing side product release, thereby maintaining stability and cytotoxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If labile ligands are used in titanium complexes to enable hydrolysis and activate cytotoxicity, then cytotoxic activity is improved, but aquatic stability deteriorates

Engineering Contradiction:
Improvecytotoxic activityVSAvoidaquatic stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent removes labile ligands from the titanium complex structure entirely, extracting the source of aquatic instability while preserving cytotoxic activity through the core salan ligand framework. This eliminates the trade-off by designing complexes that do not require hydrolysis for activation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the ligand stability parameters by using exclusively inert, non-labile ligands with strong Ti-L bonds. This parameter change transforms the complex from hydrolytically unstable to highly stable in aqueous environments while maintaining biological activity.

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If titanium complexes are made highly stable and inert by removing labile ligands, then aquatic stability is improved, but solubility and cell penetration deteriorate

Engineering Contradiction:
Improveaquatic stabilityVSAvoidcell penetration
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent segments the complex into a stable core structure with inert ligands and formulates it into nanoparticle carriers. This segmentation allows the core to maintain stability while the nanoparticle formulation provides the necessary solubility and cell penetration properties.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces nanoparticle carriers as intermediary structures that mediate between the stable but potentially insoluble titanium complexes and the biological system. These carriers enhance solubility and facilitate cell uptake without compromising the stability of the active complex.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If vanadium complexes are used to achieve high cytotoxicity, then cytotoxic activity is improved, but stability in water deteriorates

Engineering Contradiction:
Improvecytotoxic activityVSAvoidstability in water
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent removes labile ligands from vanadium complexes similar to titanium complexes, extracting the source of aquatic instability while preserving the high cytotoxic activity inherent to vanadium coordination compounds.

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentEP2888270B1Cytotoxic titanium and vanadium complexes
Publication Date: 2019.10.02 YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD
  • EP2888270B1 patent drawingFigure 1~2
  • EP2888270B1 patent drawingFigure 3A~3B
  • EP2888270B1 patent drawingFigure 4A~4B

AI summary

The present application provides a family of highly resistant and water-stable Titanium and Vanadium complexes, which may be administered directly without a further hydrolysis step and which solubility and cell-penetration characteristics may be modifiable by reducing their particle size to the nanoscale.