Core-to-surface polymerization for low-metal star polymers
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Solution Overview
Problem
The synthesis of polymeric drug delivery vehicles often results in high levels of transition metal catalyst impurities, particularly ruthenium, which are difficult to remove, limiting their medical and clinical applications.
Innovation Solution
The development of a core-to-surface polymerization process for brush-arm star polymers via ring-opening metathesis polymerization (ROMP) that incorporates additional steps to reduce ruthenium concentrations and allows for the incorporation of pharmaceutical agents, diagnostic agents, and other molecules on the nanoparticle surface, resulting in star polymers with ruthenium concentrations less than 450 ppm.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If ring-opening metathesis polymerization (ROMP) is used to synthesize brush-arm star polymers, then well-defined nanoparticles with drug and diagnostic moieties can be prepared, but high levels of ruthenium catalyst impurities are introduced that are difficult to remove
Solution Approach 1:
The patent applies extraction by removing the harmful ruthenium catalyst impurity from the nanoparticle core through a core-to-surface polymerization approach. By conducting polymerization in the core region and then transferring to the surface, the ruthenium is effectively extracted from the dense core while maintaining nanoparticle definition.
Solution Approach 2:
The patent uses an intermediary strategy by introducing a macromonomer that acts as a mediator between the catalyst and the final polymer structure. This intermediary allows the ruthenium catalyst to be present during synthesis but enables its subsequent removal while maintaining the structural integrity and definition of the nanoparticle.
2Object-generated harmful factors
If additional steps are added to reduce ruthenium concentrations, then metal impurity levels decrease to less than 450 ppm, but the synthesis process becomes more complex
Solution Approach 1:
The patent merges multiple functions into the core-to-surface polymerization process. The same polymerization steps that reduce ruthenium concentration also enable the incorporation of pharmaceutical and diagnostic agents, combining impurity reduction with functionalization in a unified approach rather than separate steps.
Solution Approach 2:
The patent creates a universal synthesis methodology that simultaneously achieves multiple objectives: reducing ruthenium impurity levels, incorporating therapeutic agents, and incorporating diagnostic agents. This multi-functional approach avoids the need for separate processes for each function.
3Object-generated harmful factors
If core-to-surface polymerization is used to generate dense BASP, then ruthenium concentration is reduced, but the process requires incorporation of additional molecules on the nanoparticle surface
Solution Approach 1:
The patent applies local quality by concentrating different functions in different regions: the core region handles ruthenium reduction through polymerization, while the surface region handles molecule incorporation. This spatial separation allows each region to optimize for its specific function without compromising the other.
Solution Approach 2:
The patent transitions from a single-phase polymerization to a multi-phase process that utilizes both core and surface dimensions. By moving the polymerization reaction from solely core-based to a core-to-surface progression, the system gains an additional dimensional control for managing both impurity reduction and functionalization.
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
This approach enables the production of polymeric nanoparticles with reduced metal impurities, enhancing their suitability for medical applications by providing a platform for diverse biomedical uses and improving the incorporation of therapeutic and diagnostic agents.
Implementation Method 1
ring-opening metathesis polymerization (ROMP) has developed into a powerful synthetic platform
Data Source
AI summary
Disclosed are methods, compositions, reagents, systems, and kits to prepare star polymers, as well as compositions and uses thereof. Various embodiments show that synthesis of these polymers contain low metal concentration to provide polymers for diverse biomedical applications including in vivo applications.