Polymer-Conjugated Thyroid Hormone Analogs for Targeted Angiogenesis Control
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Solution Overview
Problem
There is a need for thyroid hormone analogs that can bind to the cell surface receptor without entering the cell, avoiding systemic thyroid hormone actions, to treat various disorders related to angiogenesis and cancer.
Innovation Solution
Development of polymeric and nanoparticle forms of thyroid hormone analogs that conjugate with polymers like polyvinyl alcohol, acrylic acid ethylene co-polymer, or polylactic acid, allowing binding to the cell surface receptor while preventing intracellular access, and using these forms to promote or inhibit angiogenesis as needed.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thyroid hormone analogs are administered systemically, then they can treat various disorders, but they cause unwanted systemic thyroid hormone actions
Solution Approach 1:
The patent divides the thyroid hormone analog into two functional components: a polymer-conjugated portion that binds to the cell surface receptor and a separate portion that would otherwise enter the cell. The polymer conjugate (using polymers like polyvinyl alcohol, acrylic acid ethylene co-polymer, or polylactic acid) is specifically designed to be too large to enter the cell, thus segmenting the hormone's actions to occur only at the cell surface rather than systemically throughout the body.
Solution Approach 2:
The invention creates a localized action at the cell surface by conjugating the thyroid hormone analog to a polymer that restricts its activity to the extracellular space. The polymer-conjugated hormone specifically interacts with cell surface receptors (such as integrin αVβ3) without penetrating into the cell interior, thereby confining the therapeutic effect to a local site at the membrane level and preventing widespread systemic effects.
2Object-generated harmful factors
If polymer-conjugated thyroid hormone analogs are used to bind cell surface receptors, then systemic effects are avoided, but the complexity of formulation increases
Solution Approach 1:
The patent employs composite material construction by chemically conjugating thyroid hormone analogs to biocompatible polymers (such as polyvinyl alcohol, acrylic acid ethylene co-polymer, or polylactic acid). This composite structure combines the biological activity of the hormone with the size-exclusion properties of the polymer, creating a single molecular entity that binds to cell surface receptors while the polymer backbone prevents cellular internalization and simplifies the overall formulation approach.
3Object-generated harmful factors
If nanoparticle forms of thyroid hormone analogs are used, then cell surface binding is achieved without intracellular access, but manufacturing precision requirements increase
Solution Approach 1:
The patent utilizes a polymer shell or film structure by conjugating the thyroid hormone analog to a polymer chain that forms a flexible molecular envelope around the active hormone portion. This polymer shell (using polymers such as polyvinyl alcohol, acrylic acid ethylene co-polymer, or polylactic acid) is sufficiently thick and flexible to prevent cellular uptake while allowing the hormone to remain bioactive at the cell surface, effectively creating a molecular-sized protective shell that controls intracellular access.
Data Source
AI summary
Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric Nanoparticle form of thyroid hormone agonist, partial agonist or an antagonist thereof, to promote or inhibit angiogenesis in the subject. Compositions of the polymeric forms of thyroid hormone, or thyroid hormone analogs, are also disclosed.