Cationic Lipid Nanoparticle Composition to Limit Liver Accumulation

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Solution Overview

Problem

Therapeutic or prophylactic nucleic acids face challenges such as liver accumulation, reducing their efficacy at target sites due to most liposome formulations.

Innovation Solution

A cationic lipid compound and lipid nanoparticle system designed for intramuscular delivery, with specific ratios of cationic lipids and helper lipids, to enhance delivery and reduce liver enrichment, allowing high expression at injection sites and low visceral toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional liposome formulations are used for nucleic acid delivery, then delivery capacity is achieved, but liver accumulation occurs reducing efficacy at target sites

Engineering Contradiction:

Improvedelivery capacityVSAvoidliver accumulation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of cationic lipids by adjusting chain lengths (C12-C22), introducing hydroxyl groups at specific positions, and varying headgroup compositions to alter biodistribution patterns. These parameter changes enable the lipid nanoparticle to achieve high nucleic acid delivery capacity while reducing liver accumulation through optimized molecular properties that favor muscle tissue targeting.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention employs composite lipid formulations combining cationic lipids with specific chain lengths and hydroxyl substitutions alongside helper lipids. This composite approach creates lipid nanoparticles with enhanced delivery capacity to muscle tissue while minimizing liver accumulation, achieving both high efficacy at target sites and reduced off-target effects through synergistic material composition.

Inventive Principle:

Principle #40Composite materials

2Productivity

If high delivery capacity is achieved at target sites, then nucleic acid expression is enhanced, but visceral toxicity increases

Engineering Contradiction:

Improvenucleic acid expressionVSAvoidvisceral toxicity

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent designs cationic lipids with specific local structural features including hydroxyl groups at particular positions on the fatty acid chains and differentiated headgroup compositions. These local quality modifications enable the lipid nanoparticle to achieve high nucleic acid expression at muscle injection sites while reducing visceral toxicity through localized functional properties that favor target tissue uptake and reduce off-target accumulation.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20250325490A1Lipid compound, lipid nanoparticle comprising same and use thereof

Publication Date: 2025.10.23 THEMEDIUM THERAPEUTICS CO LTD

AI summary

The present disclosure provides a lipid compound, a lipid nanoparticle comprising the same and use thereof in the preparation of a drug delivery carrier. The lipid nanoparticle of the present disclosure can deliver a therapeutic or prophylactic agent (particularly a nucleic acid substance) to an injection site by intramuscular injection, and the therapeutic or prophylactic agent has high expression at the injection site but low expression in the viscera, which enables a drug to not only exert high activity but also have low visceral toxicity, and is of great significance to development and application of nucleic acid therapeutic or prophylactic agents.