Liposome Concentration via Cyclodextrin Mediator

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Solution Overview

Problem

Current methods for concentrating liposomes, such as ultracentrifugation and ultrafiltration, are laborious, expensive, and lead to irreversible aggregation, resulting in the loss of liposome characteristics, while lyophilization modifies initial characteristics upon rehydration.

Innovation Solution

A method involving the addition of cyclodextrins to liposomes in an aqueous dispersion causes flocculation and deposition, forming stable mixed liposome-cyclodextrin aggregates that can be easily lyophilized and rehydrated without altering the initial structure, allowing for reversible concentration and redispersion without the need for organic solvents or high energy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If ultracentrifugation or ultrafiltration is used to concentrate liposomes, then concentration is achieved, but the process becomes laborious, expensive, and difficult to scale industrially

Engineering Contradiction:
Improveliposome concentrationVSAvoidprocess complexity and scalability
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent introduces a mediator substance (polysorbate or hydrophilic polymer) that facilitates liposome aggregation and concentration through a simple mixing process. This intermediary agent enables concentration without requiring complex ultracentrifugation or ultrafiltration equipment, making the process easier to manufacture and scale industrially while achieving the desired liposome concentration

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If liposome flocculation or sedimentation is induced to concentrate liposomes, then concentration is achieved, but irreversible aggregation occurs and liposome characteristics are lost

Engineering Contradiction:
Improveliposome concentrationVSAvoidliposome individual characteristics
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the physicochemical parameters of the system by introducing specific mediator substances (polysorbate or hydrophilic polymers) that modify the interaction between liposomes. This controlled parameter change enables reversible aggregation through specific mechanisms (depletion attraction or steric stabilization) rather than irreversible flocculation, allowing concentration to be achieved while maintaining liposome characteristics. The mediators create controlled conditions where aggregation occurs without permanent damage to liposome structure

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The mediator substance acts as an intermediary that controls the aggregation process. Instead of direct liposome-liposome contact leading to irreversible fusion, the mediator creates a controlled aggregation mechanism where liposomes come together in a reversible manner. The mediator prevents direct harmful interactions while enabling the desired concentration effect, preserving liposome individual characteristics throughout the process

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If lyophilization is used to concentrate liposomes, then concentration is achieved, but the initial characteristics of liposomes are modified upon rehydration

Engineering Contradiction:
Improveliposome concentrationVSAvoidinitial liposome characteristics
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The mediator substance (polysorbate or hydrophilic polymer) is incorporated into the liposome system and remains present during lyophilization and rehydration. This intermediary protects liposomes during the freeze-drying process and ensures they maintain their characteristics upon rehydration. The mediator prevents direct exposure of liposomes to harsh lyophilization conditions and facilitates gentle rehydration, preserving the initial liposome properties

Inventive Principle:
Principle #24Intermediary (Mediator)

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 provides a simple, cost-effective, and scalable means to concentrate liposomes while maintaining their initial characteristics, enabling their use in various industries without altering physicochemical properties or requiring specialized equipment.

Implementation Method 1

adding cyclodextrins to liposomes in an aqueous dispersion causes the liposomes to flocculate and be deposited

Methodology Applied
Scientific EffectFlocculation: Flocculation

Implementation Method 2

These mixed aggregates are stable as they are, combine the individual properties of the liposomes and the cyclodextrins, and are further easily lyophilisable

Methodology Applied
Scientific EffectLyophilization: Freeze Drying

Data Source

PatentUS9895298B2Method for extemporaneous and reversible concentration of liposomes
Publication Date: 2018.02.20 CENT NAT DE LA RECH SCI (C N R S)
  • US9895298B2 patent drawing
  • US9895298B2 patent drawing
  • US9895298B2 patent drawing

AI summary

The invention concerns a method for extemporaneous and reversible concentration of liposomes, the mixed liposome-cyclodextrin aggregates obtainable by the method, and uses thereof in the pharmaceutical, diagnostic and cosmetic field.