Metal-Organic Coordination Polymer Composites for Bioactive Agent Release
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Solution Overview
Problem
Metal-organic frameworks (MOFs) constructed with harsh solvents and elevated temperatures can denature biological molecular species and exhibit resistance to biodegradation, limiting the efficient release of therapeutic agents.
Innovation Solution
Composite compositions using metal-organic coordination polymer matrices with polymeric chains and bioactive agents, where the polymer matrix degrades at acidic pH for controlled release, allowing for the incorporation of bioactive agents like proteins and adjuvants, and can be administered in biologically relevant solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If MOFs are constructed using harsh solvents and elevated temperatures, then the structural integrity and stability of the MOF matrix is improved, but the biological molecular species (proteins and nucleic acids) are denatured and lose their bioactivity
Solution Approach 1:
The patent changes the synthesis parameters from harsh conditions to mild conditions (aqueous solvents, room temperature, neutral pH) while maintaining MOF structural integrity. This allows the MOF matrix to form stable coordination polymers without denaturing embedded proteins or nucleic acids, resolving the contradiction between matrix stability and bioactive agent integrity
Solution Approach 2:
The patent creates composite materials where bioactive agents (proteins, nucleic acids) are integrated within the MOF matrix during synthesis. The composite structure allows the MOF to provide structural stability while the bioactive agents maintain their native conformation and function, simultaneously achieving both matrix integrity and bioactivity preservation
2Stability of the object's composition
If traditional MOFs are used, then the structural stability is maintained, but resistance to biodegradation occurs which limits efficient release of therapeutic agents
Solution Approach 1:
The patent extracts the carboxylate ligands from the MOF structure, creating carboxylate-deficient sites that are more susceptible to enzymatic degradation. This selective removal creates controlled weak points in the otherwise stable MOF matrix, enabling biodegradation and efficient therapeutic agent release while maintaining overall structural integrity during delivery
Solution Approach 2:
The patent introduces dynamic, pH-responsive coordination bonds into the MOF matrix using histidine-containing ligands. These bonds are stable at physiological pH but degrade at acidic pH values encountered in endosomes and lysosomes, creating a dynamically stable-then-degradable system that ensures both structural integrity during circulation and efficient release at the target site
3Quantity of substance
If bioactive agents are incorporated into MOFs, then the delivery capacity is improved, but the harsh synthesis conditions denature the bioactive agents
Solution Approach 1:
The patent performs preliminary action by incorporating bioactive agents into the MOF structure during the synthesis process rather than attempting to load them afterward. The mild synthesis conditions (aqueous solvents, room temperature, neutral pH) are established from the beginning, ensuring bioactive agents are embedded in their native, functional state while achieving high loading capacity within the MOF matrix
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
Enhances the delivery and efficacy of bioactive agents by maintaining their biological integrity and facilitating targeted release within phagocytic cells, improving vaccine responses and therapeutic outcomes.
Implementation Method 1
the polymer matrix degrades at acidic pH for controlled release
Implementation Method 2
L is a linker comprising a moiety for coordinating with the transition metal
Data Source
AI summary
In one aspect, composite compositions are described herein for delivery of various bioactive compositions. In some embodiments, a composite composition comprises a metal-organic coordination polymer matrix, and one or more bioactive compositions carried by the metal-organic coordination polymer matrix, wherein the metal-organic coordination polymer matrix comprises polymeric chains including a repeating unit of formula I.