Cyclodextrin Encapsulation of 3-Halopyruvates for Systemic Delivery
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Solution Overview
Problem
Current systemic administration of selective ATP inhibitors like 3-halopyruvates is hindered by their reactivity with electrophilic molecules and instability in aqueous environments, leading to increased toxicity and limited efficacy due to rapid degradation, which has restricted their use to loco-regional delivery methods.
Innovation Solution
Encapsulating 3-halopyruvates within cyclodextrins stabilizes the compound in vivo, protecting it from nucleophilic entities and providing a steady release, thereby maintaining its alkylating ability and reducing systemic toxicity, allowing for systemic administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If 3-halopyruvates are administered systemically, then they can reach tumor cells throughout the body, but they react with nucleophilic groups in proteins and degrade rapidly in aqueous environments, leading to increased toxicity and reduced efficacy
Solution Approach 1:
The patent uses cyclodextrins as intermediary carriers to encapsulate 3-halopyruvates. The cyclodextrin cavity provides a hydrophobic environment that protects the electrophilic 3-halopyruvate from nucleophilic attack by proteins and aqueous degradation, enabling systemic administration while maintaining compound stability and anticancer activity
2Quantity of substance
If the dose of 3-halopyruvates is increased to overcome rapid degradation, then more compound reaches the target, but toxicity near the injection site increases
Solution Approach 1:
The cyclodextrin encapsulation performs preliminary protection of the 3-halopyruvate before administration. This preliminary action prevents premature reaction with nucleophilic groups in the circulation, allowing the compound to reach the target with sufficient concentration without requiring dose increases that would cause local toxicity
Solution Approach 2:
Cyclodextrins act as intermediaries that control the release and delivery of 3-halopyruvates to the target site, ensuring that the compound remains stable during circulation and only becomes active when needed, thereby reducing local toxicity while maintaining effective target concentration
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 cyclodextrin encapsulation of 3-halopyruvates enhances their stability and efficacy, enabling effective systemic delivery while minimizing toxicity, as demonstrated in both in vitro and in vivo models, particularly with β-cyclodextrins providing better protection than α-cyclodextrins.
Implementation Method 1
Encapsulating 3-halopyruvates within cyclodextrins stabilizes the compound in vivo, protecting it from nucleophilic entities
Implementation Method 2
providing a steady release, thereby maintaining its alkylating ability and reducing systemic toxicity
Data Source
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AI summary
The invention provides compositions comprising cyclodextrins encapsulating a selective ATP inhibitor, as well as uses thereof.