Amphiphilic PMGA Polymers for Lipid Nanoparticle Delivery

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Solution Overview

Problem

Current lipid nanoparticles stabilized with polyethylene glycol (PEG) face challenges such as reduced interaction with target cells, immunogenicity, and the induction of anti-PEG antibodies, necessitating the development of alternative polymers for improved stability and intracellular delivery.

Innovation Solution

The use of amphiphilic poly(monoglycerol acrylate) (PMGA) polymers, which are synthesized via reversible addition-fragmentation chain-transfer polymerization and incorporate biodegradable hydrophobic groups, to form lipid particles that enhance cellular targeting and uptake while avoiding the limitations of PEG-based systems.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If polyethylene glycol (PEG) is used to stabilize lipid nanoparticles, then stability is improved, but immunogenicity increases and cellular interaction is reduced

Engineering Contradiction:

Improvelipid nanoparticle stabilityVSAvoidimmunogenicity

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical parameters of the stabilizing polymer from PEG to poly(monoglycerol acrylate) with specific molecular weights (1000-15000 Da) and compositions. This parameter change maintains the stabilizing function while eliminating immunogenicity and improving cellular interactions, as the new polymer lacks the immunogenic properties of PEG while providing comparable or superior stability through its amphiphilic structure and controlled molecular characteristics.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention uses composite material design by incorporating poly(monoglycerol acrylate) with specific hydrophobic group compositions (5-30% of total molecular weight) into the lipid nanoparticle system. This composite approach combines the benefits of polymer stabilization with the advantages of biodegradable hydrophobic groups, creating a multi-functional stabilizing agent that addresses both stability and immunogenicity concerns simultaneously.

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If polyethylene glycol (PEG) is used to stabilize lipid nanoparticles, then stability is improved, but cellular interaction is reduced

Engineering Contradiction:

Improvelipid nanoparticle stabilityVSAvoidcellular interaction

Core Design Contradiction:

Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent changes the physical and chemical parameters of the surface polymer from PEG to poly(monoglycerol acrylate) with controlled molecular weight (1000-15000 Da) and amphiphilic structure. This parameter change eliminates the steric barrier effect of PEG that prevents cellular interaction, while maintaining nanoparticle stability through the new polymer's unique properties including its hydroxyl groups and biodegradable hydrophobic segments.

Inventive Principle:

Principle #35Parameter changes

3Ease of operation

If biodegradable hydrophobic groups are incorporated into PMGA polymer, then intracellular delivery is improved, but polymer complexity increases

Engineering Contradiction:

Improveintracellular deliveryVSAvoidpolymer structure complexity

Core Design Contradiction:

Ease of operationVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the polymer structure into distinct functional segments: a hydrophilic poly(monoglycerol acrylate) backbone and separate biodegradable hydrophobic group segments (5-30% of total molecular weight). This segmentation allows each segment to perform its specific function independently - the hydrophilic backbone provides stability and biocompatibility, while the hydrophobic segments facilitate membrane interaction and intracellular delivery, simplifying the overall design despite the multi-functional requirements.

Inventive Principle:

Principle #1Segmentation

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

PMGA-based lipid particles demonstrate improved cellular internalization and stability, reduced immunogenicity, and comparable cytotoxicity to conventional polymers, making them suitable for bioactive agent delivery without prolonging circulation time or affecting osmotic stability.

Implementation Method 1

amphiphilic poly(monoglycerol acrylate) (PMGA) polymers, which are synthesized via reversible addition-fragmentation chain-transfer polymerization and incorporate biodegradable hydrophobic groups, to form lipid particles

Methodology Applied

Scientific EffectAmphiphilic polymer self-assembly: Self-Assembly

Implementation Method 2

PMGA-based lipid particles demonstrate improved cellular internalization and stability

Methodology Applied

Scientific EffectCellular internalization: Absorption (physical)

Data Source

PatentUS20240101733A1Monoglycerol acrylate based polymer and uses thereof

Publication Date: 2024.03.28 UNIVERSITE LAVAL

AI summary

The present document relates to amphiphilic poly(monoglycerol acrylate) (PMGA) polymers, comprising an hydrophilic repeating unit of monoglycerol acrylate and one or more biodegradable hydrophobic group and their use and methods of use in the delivery of bioactive agents. Additionally, the invention provides a method for preparing monoglycerol acrylate-based polymers.