Multi-Donor Nitric Oxide Macromolecules for Tunable Release
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Solution Overview
Problem
Current nitric oxide delivery systems face challenges with stability, indiscriminate release kinetics, and inability to target specific tissue types, leading to potential toxicity and undesirable side effects, limiting their therapeutic use in controlled and targeted applications.
Innovation Solution
Development of nitric oxide-releasing macromolecules with multiple nitric oxide donor structures of the same class, allowing for tunable release profiles and enhanced stability, achieved through combinations of different NO donor structures on a macromolecular framework, such as dendrimers and co-condensed silica nanoparticles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule nitric oxide donor prodrugs are used, then nitric oxide release can be achieved, but stability is poor and indiscriminate release occurs
Solution Approach 1:
The patent employs macromolecular composite structures (dendrimers, silica nanoparticles, polymers) that integrate multiple nitric oxide donor groups within a stable framework. This composite approach combines the nitric oxide-releasing functionality with the structural stability of macromolecules, resolving the contradiction between release control and stability that plagues small molecule prodrugs.
Solution Approach 2:
The patent modifies the molecular parameters by transitioning from small molecule prodrugs to macromolecular structures with controlled architecture. This parameter change in molecular size, structure, and organization enables simultaneous achievement of stability and controlled nitric oxide release kinetics that cannot be obtained with small molecules alone.
2Ease of operation
If nitric oxide is administered in gaseous form, then delivery is possible, but targeting specific tissue types is unable to be achieved
Solution Approach 1:
The patent imparts local quality to nitric oxide delivery by functionalizing macromolecules with specific targeting moieties that recognize and bind to particular tissue types or cellular structures. This enables the delivery system to concentrate nitric oxide release at specific locations rather than distributing it systemically, achieving both delivery capability and tissue targeting versatility.
Solution Approach 2:
The macromolecular structures serve as intermediaries between the nitric oxide source and the target tissue. These intermediaries provide both the delivery function and the targeting capability through their structural design, which can incorporate targeting ligands, thereby resolving the contradiction between ease of delivery and adaptability to specific tissues.
3Quantity of substance
If large amounts of nitric oxide are released, then antimicrobial activity is enhanced, but toxicity and undesirable side effects increase
Solution Approach 1:
The patent creates dynamic nitric oxide release systems where the release rate and total amount can be adjusted by modifying the macromolecular structure, such as the density of nitric oxide donor groups, the degradation rate of the macromolecule, or the environmental triggers incorporated into the design. This dynamic control enables optimization of the quantity of nitric oxide released to achieve therapeutic effects while minimizing toxicity.
4Device complexity
If monotypical nitric oxide release kinetics are used, then simplicity is maintained, but the ability to tune release profiles is limited
Solution Approach 1:
The patent segments the nitric oxide release function by incorporating multiple types of nitric oxide donor groups within the same macromolecule or using heterogeneous macromolecular populations. Each donor type can have different release kinetics, allowing the overall system to provide tunable, multi-phase release profiles while maintaining a relatively simple macromolecular platform.
Data Source
AI summary
Provided here are nitric oxide-releasing compounds that include at least two different NO donor functional groups of the same class. In some embodiments, such nitric oxide-releasing compounds are macromolecules such as dendrimer and co-condensed silica. Pharmaceutical compositions, wound dressings, kits and methods of treatments are also provided herein.