Cationic Microvesicles with Neutral Polymer Stabilization

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Solution Overview

Problem

The existing methods for preparing calibrated gas-filled microvesicles using flow-focusing microfluidic techniques fail to effectively incorporate cationic lipids due to the presence of negatively charged pegylated phospholipids, resulting in insufficient overall positive charge on the microvesicles.

Innovation Solution

A suspension of gas-filled microvesicles with a stabilizing envelope comprising a cationic lipid and a neutral or cationic amphiphilic polymeric compound, where the polymeric compound is present in a molar amount higher than 3%, and the microvesicles have a geometric standard deviation (GSD) value of at least 1.25 or lower.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If negatively charged pegylated phospholipids are used to stabilize the microvesicle envelope, then the stabilizing layer is formed and coalescence is limited, but the incorporation of cationic lipids is substantially reduced or prevented, resulting in insufficient overall positive charge

Engineering Contradiction:

Improvestabilizing layer formationVSAvoidoverall positive charge

Core Design Contradiction:

Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The patent removes the negatively charged pegylated phospholipid component from the formulation to eliminate its harmful electrostatic repulsion effect on cationic lipid incorporation, while retaining the stabilizing function through alternative neutral or cationic amphiphilic compounds

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the harmful electrostatic repulsion caused by negatively charged pegylated phospholipids into a beneficial formulation strategy by deliberately selecting neutral or cationic amphiphilic compounds that electrostatically attract and facilitate cationic lipid incorporation into the microvesicle envelope

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Manufacturing precision

If flow-focusing microfluidic techniques are used to prepare calibrated microvesicles, then narrow size distribution is achieved, but effective incorporation of cationic lipids is prevented due to presence of negatively charged pegylated phospholipids

Engineering Contradiction:

Improvesize distributionVSAvoidcationic lipid incorporation

Core Design Contradiction:

Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent changes the electrostatic parameter of the amphiphilic compound formulation from negative to neutral or positive charge, which fundamentally alters the interaction mechanism with cationic lipids during the flow-focusing microfluidic process, enabling effective incorporation while maintaining calibrated size distribution

Inventive Principle:

Principle #35Parameter changes

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 described solution achieves an overall positive charge on the microvesicles, enabling effective binding of negatively charged genetic material and enhancing the efficiency of ultrasound-mediated therapeutic treatments.

Implementation Method 1

a stabilizing envelope comprising an amphiphilic material, wherein said amphiphilic material comprises a cationic lipid and a neutral or cationic amphiphilic polymeric compound

Methodology Applied

Scientific EffectAmphiphilic self-assembly: Amphiphiles

Implementation Method 2

said amphiphilic material comprises a cationic lipid... achieving an overall positive charge on the microvesicles, enabling effective binding of negatively charged genetic material

Methodology Applied

Scientific EffectElectrostatic charge: Electrostatics

Implementation Method 3

the flow-focusing technology allows the manufacturing of calibrated microvesicles... with a geometric standard deviation (GSD) value of at least 1.25 or lower

Methodology Applied

Scientific EffectFlow-focusing: Focusing

Data Source

PatentUS12233131B2Cationic calibrated-size gas-filled microvesicles

Publication Date: 2025.02.25 BRACCO SUISSE SA

AI summary

Technical field The invention relates to new calibrated-size gas-filled microvesicles bearing an overall positive charge, to their use and to their method of manufacturing. The gas-filled microvesicles have a geometric standard deviation (GSD) value of at least 1.25 or lower and a stabilizing envelope comprising an amphiphilic material, said amphiphilic material comprising a cationic lipid and a neutral or cationic amphiphilic polymeric compound.