Core-Shell Nanostructures for Cholesterol Sequestration

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Solution Overview

Problem

Current methods for fabricating nanostructures, such as liposome nanostructures, often result in structures with large sizes, wide size distributions, and short-term stability, limiting their effectiveness in applications like drug delivery and diagnostics.

Innovation Solution

The development of nanostructures with an inorganic core surrounded by a lipid bilayer shell, where the shell is covalently or interactively attached, allowing for controlled size and stability, and incorporating proteins for enhanced functionality, specifically designed to sequester cholesterol and other lipids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional liposome fabrication methods are used, then nanostructures can be formed, but they exhibit large sizes, wide size distributions, and short-term stability

Engineering Contradiction:
ImprovestabilityVSAvoidsize distribution
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent changes the fabrication parameters by using a bottom-up self-assembly approach with specifically designed amphipathic molecules containing hydrophobic domains and hydrophilic domains. This molecular design enables controlled assembly into nanostructures with uniform sizes (20-100 nm), resolving the contradiction between stability and size distribution control

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite nanostructures by combining hydrophobic domains (for cholesterol sequestration) with hydrophilic domains (for aqueous solubility and stability). This composite molecular architecture enables both long-term stability in physiological environments and precise size control through controlled self-assembly

Inventive Principle:
Principle #40Composite materials

2Manufacturing precision

If traditional liposome fabrication methods are used, then nanostructures can be formed, but they have large sizes and uncontrolled dimensions

Engineering Contradiction:
Improvesize controlVSAvoidnanostructure size
Core Design Contradiction:
Manufacturing precisionVSLength of moving object

Solution Approach 1:

The patent employs parameter changes by designing amphipathic molecules with specific hydrophobic and hydrophilic domain ratios that dictate self-assembly into nanostructures of controlled size (20-100 nm). The molecular parameters directly control the resulting nanostructure dimensions, enabling precise size control

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent segments the molecular structure into distinct hydrophobic domains and hydrophilic domains. This segmentation enables controlled self-assembly where the hydrophobic domains aggregate to form the core while hydrophilic domains form the outer shell, precisely controlling the nanostructure size and morphology

Inventive Principle:
Principle #1Segmentation

3Reliability

If nanostructures are designed to sequester cholesterol through hydrophobic interaction, then therapeutic effectiveness is improved, but structural complexity increases

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidstructural complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies local quality by concentrating hydrophobic character specifically in the domains that interact with cholesterol, while other parts of the molecule maintain hydrophilic character for solubility. This localized functional differentiation enables effective cholesterol sequestration without requiring complex overall structures

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent designs amphipathic molecules that perform multiple functions: the hydrophobic domains sequester cholesterol, the hydrophilic domains provide aqueous solubility and stability, and the overall structure enables controlled self-assembly. This multi-functionality in a single molecular design reduces the need for additional complex structural components

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 resulting nanostructures are stable, have controlled size distributions, and can effectively sequester cholesterol, making them suitable for diagnosing, preventing, and treating diseases associated with abnormal lipid levels, while being cost-effective and scalable for therapeutic use.

Implementation Method 1

the shell being able to sequester cholesterol through hydrophobic interaction

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 2

forming a layer of the plurality of components on the surface of the nanostructure core by self-assembly

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Data Source

PatentEP2288336B8Nanostructures suitable for sequestering cholesterol
Publication Date: 2017.03.22 NORTHWESTERN UNIV
  • EP2288336B8 patent drawing
  • EP2288336B8 patent drawing

AI summary

Articles, compositions, kits, and methods relating to nanostructures, including those that can sequester molecules such as cholesterol, are provided. Certain embodiments described herein include structures having a core-shell type arrangement; for instance, a nanoparticle core may be surrounded by a shell including a material, such as a lipid bilayer, that can interact with cholesterol and/or other lipids. In some embodiments, the structures, when introduced into a subject, can sequester cholesterol and/or other lipids and remove them from circulation. Accordingly, the structures described herein may be used to diagnose, prevent, treat or manage certain diseases or bodily conditions, especially those associated with abnormal lipid levels.