Nucleic Acid-Containing Lipid Nanoparticles with Three Hydrocarbon Groups

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Solution Overview

Problem

Existing methods struggle to produce nucleic acid-containing lipid nanoparticles that are both stable and small in size, which is crucial for efficient delivery to tumors and other cellular targets.

Innovation Solution

The use of a lipid with a hydrophilic unit having one quaternary ammonium group and three independent hydrocarbon groups, combined with a lipid derivative or fatty acid derivative of a water-soluble polymer, to form nucleic acid-containing lipid nanoparticles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If conventional cationic lipids with two hydrocarbon groups are used to form nucleic acid-containing lipid nanoparticles, then the nanoparticles can be produced with adequate stability, but the particle size remains large (50-100 nm) which limits delivery efficiency to tumors

Engineering Contradiction:
Improvenanoparticle stabilityVSAvoidnanoparticle size
Core Design Contradiction:
Stability of the object's compositionVSVolume of moving object

Solution Approach 1:

The patent changes the structural parameters of the cationic lipid by using lipids with three hydrocarbon groups instead of the conventional two hydrocarbon groups. This structural parameter change results in nanoparticles with reduced size (82-95 nm) while maintaining stability, thereby resolving the contradiction between stability and size.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a composite lipid structure combining a quaternary ammonium group (hydrophilic) with three hydrocarbon groups (hydrophobic). This composite structure enables the formation of smaller, more stable nanoparticles by optimizing both hydrophilic-hydrophobic balance and molecular packing, thus achieving both reduced size and maintained stability.

Inventive Principle:
Principle #40Composite materials

2Productivity

If the particle size of lipid nanoparticles is reduced to enhance delivery efficiency to tumors, then delivery efficiency improves, but the stability of the nanoparticles deteriorates

Engineering Contradiction:
Improvedelivery efficiencyVSAvoidnanoparticle stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

By changing the lipid structural parameter from two to three hydrocarbon groups, the patent achieves optimal nanoparticle size (82-95 nm) that enhances delivery efficiency while simultaneously maintaining stability. The three hydrocarbon groups provide sufficient hydrophobic interaction for stability even at reduced particle size.

Inventive Principle:
Principle #35Parameter changes

3Volume of moving object

If cationic lipids with more hydrocarbon groups are used to reduce nanoparticle size, then particle size decreases improving delivery, but the complexity of lipid structure increases

Engineering Contradiction:
Improvenanoparticle sizeVSAvoidlipid structure complexity
Core Design Contradiction:
Volume of moving objectVSDevice complexity

Solution Approach 1:

The patent applies a moderate parameter change by using three hydrocarbon groups in the cationic lipid structure. This represents a simple increment from conventional two-group lipids, achieving reduced nanoparticle size without excessive structural complexity. The quaternary ammonium core with three attached hydrocarbon groups maintains structural simplicity while delivering the desired size reduction.

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 resulting nanoparticles are more stable and smaller, enhancing their delivery efficiency and physiological activity, particularly for gene suppression and permeability in cellular environments.

Implementation Method 1

a lipid having a hydrophilic unit having one quaternary ammonium group and three independent, optionally substituted hydrocarbon groups

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentEP3275448B1Nucleic acid-containing lipid nanoparticles
Publication Date: 2025.10.29 KYOWA HAKKO KIRIN CO LTD
  • EP3275448B1 patent drawingFigure 1
  • EP3275448B1 patent drawingFigure 2
  • EP3275448B1 patent drawingFigure 3

AI summary

The present invention provides nucleic acid-containing lipid nanoparticles containing a lipid (lipid A) which has a hydrophilic unit having a single quaternary ammonium group, and three independent, optionally substituted hydrocarbon groups, a lipid derivative or fatty acid derivative of a water-soluble polymer, and a nucleic acid.