Elastin-like polypeptide carrier for placental barrier control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapeutic agents often cross the placental barrier during pregnancy, posing risks to the developing fetus, as they are not effectively contained within the maternal circulation, leading to adverse effects on fetal development.
Innovation Solution
A composition comprising an elastin-like polypeptide (ELP) coupled with a therapeutic agent, specifically designed to reduce the amount of the therapeutic agent crossing the placenta, utilizing ELP sequences with repeating units like VPGXG and coupled with cell-penetrating or organ-targeting peptides to enhance delivery and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic agents are administered to pregnant mothers, then therapeutic efficacy in the mother is improved, but the amount of therapeutic agent crossing the placenta increases causing adverse effects on the developing fetus
Solution Approach 1:
The patent uses an elastin-like polypeptide (ELP) as an intermediary carrier that binds to therapeutic agents. This ELP-therapeutic agent conjugate acts as a mediator that prevents direct passage of the therapeutic agent across the placenta while still allowing the therapeutic effect to be achieved in the mother through cellular uptake mechanisms.
Solution Approach 2:
The patent creates a composite material system combining the elastin-like polypeptide carrier with the therapeutic agent. This composite ELP-therapeutic agent conjugate has properties that allow it to remain in the maternal circulation and be taken up by maternal cells while preventing placental transfer, thus resolving the contradiction between therapeutic efficacy and fetal safety.
2Reliability
If therapeutic agents are administered to pregnant mothers, then therapeutic efficacy is improved, but side effects in the mother increase
Solution Approach 1:
The ELP serves as a carrier intermediary that delivers the therapeutic agent to specific maternal cells through cellular uptake mechanisms. This targeted delivery approach reduces non-specific distribution and minimizes side effects while maintaining therapeutic efficacy at the target site.
Solution Approach 2:
The patent employs cell-penetrating peptides and organ-targeting peptides to confer local specificity on the ELP-therapeutic agent conjugate. This ensures the therapeutic agent is delivered to specific maternal cells or organs where it is needed, reducing systemic side effects while maintaining local therapeutic efficacy.
3Ease of operation
If conventional delivery methods are used, then ease of administration is maintained, but control over therapeutic agent distribution is insufficient
Solution Approach 1:
The ELP-therapeutic agent conjugate system maintains ease of administration through simple intravenous or oral delivery while achieving precise control over distribution through the inherent properties of the ELP carrier and its ability to be taken up by cells and prevent placental transfer. The system provides both ease of administration and distribution control simultaneously.
Solution Approach 2:
The patent utilizes the thermal responsiveness of the elastin-like polypeptide, which undergoes a sol-gel transition at specific temperatures. This parameter change in the ELP's physical state can be exploited to control its binding and release properties, thereby precise control over therapeutic agent distribution while maintaining ease of administration.
Data Source
Figure 1
Figure 2A~2B
Figure 3A~3D
AI summary
A composition including an elastin-like polypeptide (ELP) coupled to a therapeutic agent is provided. The ELP comprises at least about 5 repeats of the amino acid sequence VPGXG. Further provided is a method of using the composition for therapeutic agent delivery during pregnancy to reduce the amount of the therapeutic agent crossing a placenta in a pregnant subject. The method includes administering to the pregnant subject an effective amount of the composition comprising the ELP coupled to the therapeutic agent.