Lyophilized Lipid Nanoparticles With pH Buffer Exchange for Gene Delivery

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing methods for lyophilizing nucleic acid-encapsulating lipid nanoparticles fail to maintain gene delivery efficiency and stability during storage and rehydration, with varying properties depending on the ratio of ionic lipids and other components.

Innovation Solution

Prepare nucleic acid-encapsulating lipid nanoparticles in an acidic buffer, exchange the buffer to a pH range of 4.5 to 6.9, and then lyophilize, using specific ionic lipids and a cryoprotectant to stabilize the composition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cationic liposomes using quaternary amine are used to form lipoplex, then nucleic acid delivery is achieved, but particle size control becomes difficult and cytotoxicity increases

Engineering Contradiction:

Improvenucleic acid deliveryVSAvoidcytotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical structure parameter of the lipid from quaternary amine (permanent positive charge) to tertiary amine (pH-dependent charge). This parameter change allows the lipid to be positively charged at acidic pH for nucleic acid complexation, but neutral at physiological pH to reduce cytotoxicity, thus resolving the contradiction between delivery effectiveness and safety.

Inventive Principle:

Principle #35Parameter changes

2Stability of the object's composition

If lipid nanoparticles are lyophilized for storage, then stability is improved, but gene delivery efficiency decreases after rehydration

Engineering Contradiction:

Improvestorage stabilityVSAvoidgene delivery efficiency

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The patent applies preliminary action by incorporating a cryoprotectant (sugar or polyol) into the lipid nanoparticle formulation before lyophilization. This cryoprotectant forms a protective matrix during freezing and drying that preserves the nanoparticle structure and prevents aggregation, ensuring that gene delivery efficiency is maintained after rehydration despite the stability improvements from lyophilization.

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

The method maintains high gene delivery efficiency and stability during storage, ensuring effective nucleic acid transfer into cells and living organisms.

Implementation Method 1

Utilizing the electrostatic interaction of quaternary amine with nucleic acid

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

attempts have been made to lyophilize lipid nanoparticles encapsulating nucleic acid

Methodology Applied

Scientific EffectLyophilization: Freeze Drying

Data Source

PatentUS20260034242A1Lyophilized composition of nucleic-acid-loaded lipid nanoparticles

Publication Date: 2026.02.05 NOF CORP

AI summary

The present invention provides a lyophilized composition of nucleic acid-encapsulating lipid nanoparticles having a pH of 4.5 or more and 6.9 or less, including an ionic lipid represented by the formula (1):wherein symbols are as defined in the DESCRIPTION.