In Situ Solidifying Complex Coacervates for Embolic Agents
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Solution Overview
Problem
Current embolic agents, such as cyanoacrylate and Onyx, face challenges including difficulty in control, rapid polymerization, and toxicity limitations, making them unsuitable for effective and safe use in medical applications.
Innovation Solution
The development of fluid complex coacervates composed of oppositely charged polyelectrolytes that convert into solid adhesives in situ at physiological ionic strength, providing a controlled and biocompatible embolic solution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If cyanoacrylate monomers are used as embolic agents, then rapid polymerization occurs upon contact with water, but this makes the agent difficult to control and can glue the catheter to blood vessels
Solution Approach 1:
The patent applies preliminary action by pre-mixing the polycation and polyanion components in a controlled environment to form a complex coacervate that remains stable during storage and injection. The actual gelation reaction is triggered only after injection into the target vessel, allowing controlled delivery while maintaining rapid final setting. This resolves the contradiction by separating the mixing phase (controlled) from the polymerization phase (rapid but localized).
Solution Approach 2:
The complex coacervate acts as an intermediary state between the liquid injectable form and the final solid gel. The coacervate contains pre-associated polyelectrolyte complexes that remain fluid during injection but rapidly solidify upon contact with physiological conditions. This intermediary form enables both easy injection and rapid setting, resolving the control versus speed contradiction.
2Ease of operation
If Onyx is used as an embolic agent, then it can be injected into blood vessels, but the DMSO solvent toxicity limits the amount that can be used
Solution Approach 1:
The patent uses biocompatible, biodegradable polyelectrolytes that are safe for in vivo use and can be eliminated by the body. These materials replace toxic solvents like DMSO with inherently safe components. The system uses water-soluble polycations and polyanions that degrade into non-toxic products, eliminating solvent toxicity while maintaining injectability.
Solution Approach 2:
The patent changes the fundamental parameter of solvent composition from toxic organic solvents (DMSO) to water-based physiological solutions. This parameter change eliminates toxicity while preserving injectability. The gelation mechanism is changed from solvent diffusion/precipitation to ionic crosslinking in physiological conditions, allowing unlimited dosage without toxicity concerns.
3Manufacturing precision
If fluid complex coacervates are designed to solidify in situ at physiological ionic strength, then precise control over adhesion and gelation is achieved, but the formulation complexity increases
Solution Approach 1:
The complex coacervate system is self-regulating, using the physiological ionic strength of the target environment as the trigger for gelation. The polyelectrolyte complexes automatically adjust their assembly state in response to local salt concentration, pH, and temperature conditions. This self-service mechanism eliminates the need for external triggers or complex control systems, achieving precise control without proportional increases in formulation complexity.
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 in situ solidifying complex coacervates offer precise control over adhesion and gelation, reducing the risk of tissue damage and improving the safety and efficacy of embolic procedures.
Implementation Method 1
fluid complex coacervates that produce solid adhesives in situ. Oppositely charged polyelectrolytes were designed to form fluid adhesive complex coacervates at ionic strengths higher than the ionic strength of the application site, but an insoluble adhesive solid or gel at the application site
Implementation Method 2
the fluid adhesive complex coacervate is converted to an adhesive solid or gel as the salt concentration in the complex coacervate equilibrates to the application site salt concentration
Data Source
AI summary
Described herein are fluid complex coacervates that produce solid adhesives in situ. Oppositely charged polyelectrolytes were designed to form fluid adhesive complex coacervates at ionic strengths higher than the ionic strength of the application site, but an insoluble adhesive solid or gel at the application site. When the fluid, high ionic strength adhesive complex coacervates are introduced into the lower ionic strength application site, the fluid complex coacervate is converted to a an adhesive solid or gel as the salt concentration in the complex coacervate equilibrates to the application site salt concentration. In one embodiment, the fluid complex coacervates are designed to solidify in situ at physiological ionic strength and have numerous medical applications. In other aspects, the fluid complex coacervates can be used in aqueous environment for non-medical applications.