Porous Substrate Protein Delivery with Cyclodextrin

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Solution Overview

Problem

Proteins stored on porous substrates often experience aggregation and denaturation due to large air-water interfaces, which existing storage and delivery methods fail to adequately address, leading to instability and reduced effectiveness.

Innovation Solution

The use of a porous substrate with a protein aggregation modifying agent, such as cyclodextrin, for reversible immobilization and elution of proteins, which reduces aggregation by displacing proteins from the air-water interface and maintaining stability during storage and delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If proteins are stored on porous substrates using conventional methods, then storage is achieved, but protein aggregation and denaturation occur due to large air-water interfaces

Engineering Contradiction:
Improveprotein stabilityVSAvoidaggregation and denaturation
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

Cyclodextrin acts as an intermediary substance between the protein and the air-water interface. It binds to the air-water interface through its hydrophobic cavity, preventing direct contact between the protein and the interface, thereby eliminating the harmful effect of aggregation and denaturation while maintaining protein stability during storage on porous substrates

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the chemical composition parameter of the storage environment by introducing cyclodextrin. This alters the properties of the air-water interface, transforming it from a harmful surface that causes aggregation to a modified interface that protects protein stability while maintaining reversible immobilization

Inventive Principle:
Principle #35Parameter changes

2Duration of action of stationary object

If proteins are reversibly immobilized on porous substrates for extended storage, then storage duration is improved, but protein aggregation increases due to prolonged exposure to air-water interfaces

Engineering Contradiction:
Improvestorage durationVSAvoidprotein aggregation
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

Cyclodextrin serves as a protective intermediary that remains present throughout the extended storage period. It continuously occupies the air-water interfaces on the porous substrate, preventing aggregation even during long-term storage, thereby enabling extended storage duration without the usual increase in protein aggregation

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The cyclodextrin is applied in advance to the porous substrate before protein immobilization. This preliminary action ensures that the air-water interfaces are pre-occupied by cyclodextrin, creating a protective environment that prevents aggregation from the beginning of storage and maintains protein stability throughout the extended storage period

Inventive Principle:
Principle #10Preliminary action

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

This method effectively reduces protein aggregation and denaturation, allowing for the efficient delivery of non-aggregated proteins, with the cyclodextrin agent protecting the proteins from denaturation and aggregation during the immobilization, storage, and elution processes.

Implementation Method 1

reduces aggregation by displacing proteins from the air-water interface

Methodology Applied
Scientific EffectSurface tension: Surface Tension

Implementation Method 2

providing a porous substrate comprising a reversibly immobilized protein

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentEP3024843B1Enhanced functionality and delivery of a protein from a porous substrate
Publication Date: 2022.08.31 BIO RAD LABORATORIES INC
  • EP3024843B1 patent drawingFigure 1
  • EP3024843B1 patent drawingFigure 2
  • EP3024843B1 patent drawingFigure 3

AI summary

Compositions, methods, articles of manufacture, and kits are provided for storage and delivery of proteins.