Embolic Membrane-Active Composition for Lower-Field Tumor Electroporation
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Solution Overview
Problem
Existing methods for biological tissue destruction, such as thermal ablation and irreversible electroporation, lack innovative compositions and combination approaches for effective tumor treatment.
Innovation Solution
A solid embolic composition comprising releasable membrane-active agents like poly(6-aminohexyl methacrylate), poly(aminoethyl-co-butyl methacrylate), and poly(2-hexamethyleneimino)ethyl methacrylate, administered to a target site, followed by irreversible electroporation (IRE) to enhance tissue destruction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thermal ablation or conventional IRE is used for tissue destruction, then tumor treatment is achieved, but high electric field strength is required and treatment efficacy is limited
Solution Approach 1:
The patent applies preliminary action by administering membrane-active agents to the target tissue before applying the electric field. These agents are delivered via embolic compositions that are injected into the tumor vasculature, allowing the agents to accumulate in the tumor tissue beforehand. This pre-treatment sensitizes the cells to electroporation, enabling effective tumor destruction at lower electric field strengths than conventional IRE
Solution Approach 2:
The patent changes the biochemical parameters of the target tissue by introducing membrane-active agents that alter cell membrane properties. These agents modify the membrane structure and composition, making it more susceptible to electroporation. This parameter change allows the electric field to achieve greater membrane disruption at lower intensities, thereby reducing the energy required for treatment while improving efficacy
2Reliability
If high concentration of membrane-active agents is used to enhance IRE efficacy, then cell killing efficacy increases, but systemic toxicity may increase
Solution Approach 1:
The patent applies local quality by concentrating membrane-active agents specifically at the tumor site through embolic composition injection into the tumor vasculature. The embolic particles become trapped in the tumor's blood vessels, creating a high local concentration of membrane-active agents within the tumor while maintaining low systemic concentrations. This localized delivery ensures enhanced IRE efficacy at the target site without exposing healthy tissues to high levels of the agents
Solution Approach 2:
The patent uses embolic compositions as an intermediary delivery system for the membrane-active agents. These embolic particles serve as carriers that transport the agents through the bloodstream and selectively deposit them in the tumor tissue. The embolic composition acts as a mediator between the systemic circulation and the local tumor site, enabling controlled local release of high agent concentrations without requiring high systemic levels, thereby reducing systemic toxicity
3Ease of operation
If embolic compositions are administered to deliver membrane-active agents, then controlled local release is achieved, but treatment procedure complexity increases
Solution Approach 1:
The patent merges multiple functions into a single embolic composition formulation. The embolic particles simultaneously serve as: (1) a delivery vehicle for membrane-active agents, (2) an embolic material to occlude tumor vasculature, and (3) a localized reservoir for controlled agent release. This combination of functions into one integrated system achieves controlled local release without requiring separate administration steps for each function, thereby limiting the increase in procedural 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 combination of embolic compositions and IRE increases cell killing efficacy and reduces the electric field strength required for tumor treatment, offering controlled release profiles and biostability.
Implementation Method 1
Cationic molecules bind to cell membrane via charge-charge attraction
Implementation Method 2
Amphiphilic molecules bind to cell membrane via charged functional groups and with cell membrane lipids via hydrophobic interaction
Implementation Method 3
performing treatment of the tissue volume by application of a pulsed electric field to the tissue volume, for example, irreversible electroporation
Data Source
Figure 1A~1D
Figure 2A~3
Figure 4A~4B
AI summary
In some aspects, the present disclosure pertains to methods of treating a tissue volume comprising (a) administering an implantable composition comprising a releasable membrane-active agent to a target site such that the membrane-active agent is locally released to the tissue volume and (b) performing irreversible, reversible and/or thermal treatment by application of a pulsed electric field to the tissue volume. In other aspects, the present disclosure pertains to embolic compositions that comprise releasable membrane-active agents.