Ionizable Lipid Nanoparticles for Nucleic Acid Delivery

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Solution Overview

Problem

Existing lipid nanoparticles (LNPs) for delivering biomacromolecules like nucleic acids face challenges in penetrating cell membranes due to their hydrophilicity and stability issues, which limits their delivery efficiency and stability in vivo.

Innovation Solution

An ionizable lipid compound with an optimized hydrophobic carbon chain length and an amine head structure is developed, which enhances the delivery efficiency of active molecules such as nucleic acids by forming lipid nanoparticles that can effectively interact with and penetrate cell membranes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If the hydrophobic carbon chain length of ionizable lipid is increased to 12-18 carbon atoms, then the stability of lipid nanoparticles is improved, but the delivery efficiency of nucleic acids decreases

Engineering Contradiction:

Improvestability of lipid nanoparticlesVSAvoiddelivery efficiency of nucleic acids

Core Design Contradiction:

Stability of the object's compositionVSProductivity

Solution Approach 1:

The patent applies parameter changes by optimizing the hydrophobic carbon chain length to a specific range (8-10 carbon atoms) rather than using the conventional 12-18 carbon atoms. This parameter optimization resolves the contradiction by finding the optimal balance point where delivery efficiency is maximized while maintaining sufficient stability, demonstrating that neither too long nor too short chains are ideal.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies local quality by making the hydrophobic chain length different from conventional lipids (shorter at 8-10 carbons vs. 12-18 carbons) to achieve superior local interaction properties with cell membranes. This localized structural modification enables the lipid to penetrate cell membranes more effectively while maintaining nanoparticle stability through other structural features.

Inventive Principle:

Principle #3Local quality

2Productivity

If the hydrophobic carbon chain length is decreased below 12 carbon atoms, then the delivery efficiency increases, but the stability of lipid nanoparticles deteriorates

Engineering Contradiction:

Improvedelivery efficiency of nucleic acidsVSAvoidstability of lipid nanoparticles

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent resolves this contradiction by precisely optimizing the hydrophobic chain length parameter to 8-10 carbon atoms, which is shorter than conventional lipids but not excessively short. This optimized parameter range achieves high delivery efficiency while preventing stability deterioration through complementary structural features of the ionizable lipid.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies composite materials by combining the optimized short hydrophobic chain (8-10 carbons) with specific ionizable amine head groups and other lipid components to create a composite lipid structure. This composite approach allows the short chain to provide high delivery efficiency while other structural elements compensate for potential stability losses.

Inventive Principle:

Principle #40Composite materials

3Reliability

If the ionizable lipid compound is designed with optimized carbon chain length, then the interaction with cell membranes is improved, but the complexity of lipid nanoparticle formulation increases

Engineering Contradiction:

Improveinteraction with cell membranesVSAvoidcomplexity of lipid nanoparticle formulation

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by defining a specific optimized range (8-10 carbon atoms) for the hydrophobic chain length, which simplifies the formulation process by providing clear design guidelines. Rather than requiring complex trial-and-error optimization, the specified parameter range enables more straightforward nanoparticle formulation while maintaining reliable cell membrane interaction.

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 optimized ionizable lipid compound increases the delivery efficiency of nucleic acids and other active molecules by improving the stability and interaction of lipid nanoparticles with cell membranes, leading to enhanced therapeutic potential.

Implementation Method 1

The amine head part (amine head) of the cationic lipid or ionizable lipid can promote the binding and encapsulation of the LNP and a biomacromolecule, through electrostatic interaction with the biomacromolecule

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

the hydrophobic carbon chain length of cationic lipids or ionizable lipids affects stability of LNPs and the efficiency of drug encapsulation and delivery

Methodology Applied

Scientific EffectHydrophobic interaction: Hydrophobe

Data Source

PatentUS20250179015A1Degradable lipid for active molecule delivery and lipid nanoparticle thereof

Publication Date: 2025.06.05 BEIJING CARRIUS BIO LTD

AI summary

The present invention provides an ionizable lipid compound having an optimized carbon chain length and an amine head so that the ionizable lipid compound has increased delivery efficiency for an active molecule including, but not limited to, nucleic acids, proteins, small molecule drugs and the like. The present invention further relates to a lipid nanoparticle (LNP) comprising the ionizable lipid compound and the active molecule, and a pharmaceutical composition comprising the lipid nanoparticle.