Silk-Elastinlike Protein Chemoembolic Agents for Sustained Drug Release
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Solution Overview
Problem
Current embolic agents for transarterial chemoembolization, such as drug-eluting beads and liquid embolic agents, face limitations in penetrating to the arterio-capillary level of tumor vessels and achieving sustained, localized delivery of anti-cancer agents, leading to reduced efficacy and increased toxicity due to burst release of drugs from solvents like DMSO.
Innovation Solution
Development of chemoembolic compositions comprising silk-elastinlike protein polymers that convert to hydrogels upon administration, allowing for reduced blood flow to tumors and sustained, localized release of anti-cancer agents, thereby reducing systemic toxicity and improving treatment outcomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If liquid embolic agents dissolved in DMSO are used, then embolization can be achieved, but burst release of drugs occurs causing acute local toxicity and transient therapeutic effects
Solution Approach 1:
The patent changes the physical state parameter of the embolic agent from liquid to solid (amorphous glassy state), and changes the solvent system from DMSO to aqueous buffer, thereby eliminating burst release and acute toxicity while maintaining embolization efficacy
Solution Approach 2:
The patent utilizes phase transition by forming an amorphous glassy solid from an aqueous solution that remains stable during storage and only transitions to a gel state upon administration, enabling controlled drug release without burst effect
2Adaptability or versatility
If drug-eluting beads are used, then localized drug delivery can be achieved, but only charged low molecular weight drugs can be incorporated limiting drug selection
Solution Approach 1:
The amorphous glassy matrix provides a universal incorporation mechanism that can accommodate various types of anti-cancer agents including neutral, acidic, and basic drugs regardless of molecular weight, eliminating the limitations of ion exchange methods
Solution Approach 2:
The patent changes the incorporation mechanism from ion exchange (requiring charged drugs) to physical entrapment in an amorphous matrix, thereby expanding drug compatibility to include neutral and high molecular weight drugs
3Volume of moving object
If non-degradable polymer DEBs are used, then embolization can be achieved, but finite size limits penetration to arterio-capillary level reducing total tumor volume exposure
Solution Approach 1:
The patent creates a degradable amorphous glassy embolic agent that dynamically changes from a solid state during injection to a gel state in vivo, and further degrades over time to release drugs and allow macrophage clearance, enabling better tissue penetration and distribution
Solution Approach 2:
The embolic agent is designed to preliminarily occlude vessels to establish localized high drug concentration, then gradually degrade to allow macrophage-mediated clearance and further distribution to smaller vessels, maximizing tumor volume exposure
4Duration of action of moving object
If DEB drug delivery relies on concentration gradient and diffusive mechanisms, then drug release can occur, but release rate is limited and sustained delivery over days or weeks is difficult to achieve
Solution Approach 1:
The degradable amorphous glassy matrix provides periodic drug release by combining initial concentration gradient-driven release with sustained release during degradation, creating a multi-phase release pattern that maintains therapeutic levels over extended periods
Solution Approach 2:
The patent creates a composite system combining amorphous glassy matrix with degradable polymer components, enabling both sustained release through matrix degradation and controlled release through polymer erosion, achieving prolonged therapeutic effect
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 silk-elastinlike protein polymer-based compositions effectively reduce tumor volume and inhibit growth by providing sustained release of anti-cancer agents, minimizing systemic toxicity and allowing patients to adhere to the original treatment schedule, leading to improved patient outcomes.
Implementation Method 1
The compositions are liquids prior to administration to a subject but convert to hydrogels upon administration to the subject
Data Source
AI summary
Described herein are chemoembolic compositions and agents. The compositions include one or more anti-cancer agents and a silk-elastinlike protein polymer, wherein the compositions are liquids prior to administration to a subject but convert to hydrogels upon administration to the subject. Administration of the Chemoembolic compositions to tumor and/or tumor vasculature in a subject having cancer can result in reduced or inhibited blood flow to the tumor as well as localized, sustained release of the anti-cancer agent in the vicinity of the tumor. Reduction in blood flow, in turn, results in a reduction of tumor volume and/or inhibition of tumor growth, while localized release of the anti-cancer agent results in reduced systemic effects and lower overall toxicity of treatment with the compositions.