Cyclodextrin-Polymer Conjugates for Cholesterol Clearance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapeutic agents for lipid storage disorders, such as Niemann-Pick type C disease, face challenges due to rapid clearance from the body, leading to toxicity and adverse effects from high doses required to maintain effective concentrations, and lack of effective treatments for these conditions.
Innovation Solution
Development of cyclodextrin-based polymers with a triazole-ketal-triazole linker structure that prolongs the circulation of cyclodextrin derivatives in the body, allowing for improved bioavailability and permeation across the blood-brain barrier, effectively reducing cholesterol levels in cells and tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If hydrophilic molecules like cyclodextrin are used to treat lipid storage disorders, then they can effectively remove excess lipids from cells, but they undergo rapid clearance from the bloodstream requiring high concentrations or repeated administration
Solution Approach 1:
The patent applies composite materials by combining cyclodextrin molecules with hydrophobic polymers to create amphiphilic conjugates. These conjugates integrate the lipid-binding capability of cyclodextrin with the prolonged circulation properties of hydrophobic polymer backbones, resolving the contradiction between effective lipid removal and rapid clearance from bloodstream
Solution Approach 2:
The patent changes the physical-chemical parameters of cyclodextrin by modifying its hydrophilicity through conjugation with hydrophobic polymers. This parameter change transforms the pharmacokinetic profile, extending circulation half-life while maintaining the ability to bind and remove lipids from cells
2Quantity of substance
If high concentrations of hydrophilic therapeutic agents are administered to maintain effective levels, then minimum effective concentration is maintained, but toxicity and adverse effects to organs increase
Solution Approach 1:
By creating composite structures of cyclodextrin-conjugated-polymer, the patent achieves prolonged circulation at lower doses, thereby maintaining effective concentrations without the toxicity associated with high-dose administration of unmodified hydrophilic agents
Solution Approach 2:
The patent transforms the short-lived cyclodextrin molecule into a long-circulating therapeutic by attaching it to a polymer backbone, effectively creating a sustained-release system that reduces the need for repeated high-dose administrations
3Quantity of substance
If conventional treatments like dietary reduction or Low Density lipoprotein receptor knock-out are used, then cholesterol storage is reduced, but no significant therapeutic benefit is achieved
Solution Approach 1:
The patent introduces cyclodextrin-conjugated-polymer as an intermediary substance that directly binds to and removes excess cholesterol from cells, providing a more reliable therapeutic mechanism compared to conventional approaches that only reduce cholesterol storage without ensuring effective removal
Solution Approach 2:
The patent directly extracts and removes excess cholesterol from cells using the cyclodextrin moieties in the conjugate, which specifically bind to and sequester lipid molecules, providing reliable therapeutic benefit beyond mere storage reduction
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-based polymers significantly increase cholesterol clearance from cells, delay the onset of symptoms, and extend the lifespan of affected mice, demonstrating improved therapeutic efficacy with reduced dosing frequency and minimized toxicity.
Implementation Method 1
cyclodextrin, which are generally employed to treat lipid storage disorders
Data Source
Figure 1~2
Figure 3
Figure 4
AI summary
The present disclosure relates to polymers comprising conjugates of cyclodextrin or derivatives thereof and a linker moiety, methods of preparing the same and their application in the removal of lipids such as cholesterol from cells in treating lipid storage disorders. The present polymers exhibit improved properties including but not limiting to improved biocompatibility, improved retention time, prolonged duration of action in cells, and increased efficacy in removal of cholesterol from cells in treating lipid storage disorders.