Block Copolymer Vesicles for Stable Drug Delivery

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Solution Overview

Problem

Amphiphilic copolymers, particularly those involving ethylene oxide, face challenges due to its flammability, toxicity, and difficulty in functionalization and cross-linking, limiting their application in forming stable and functional vesicles for drug delivery and membrane formation.

Innovation Solution

Block copolymers comprising (poly)2-C 1-3 alkyl-2-oxazoline and polybutadiene blocks with specific end groups, such as carboxy, amine, or alkyne, are used to form vesicles that are easy to stabilize and functionalize, offering low permeability and tailored size for drug delivery and membrane applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ethylene oxide-based copolymers are used to form vesicles, then vesicle formation is achieved, but the copolymers suffer from flammability, toxicity, and difficulty in functionalization and cross-linking

Engineering Contradiction:
Improvevesicle stabilityVSAvoidflammability and toxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and replaces the problematic ethylene oxide component with alternative hydrophilic blocks such as poly(2-methyl-2-oxazoline) and poly(2-ethyl-2-oxazoline), eliminating the flammability and toxicity associated with ethylene oxide while preserving the amphiphilic structure necessary for vesicle formation

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention creates composite block copolymers combining hydrophilic oxazoline blocks with hydrophobic polybutadiene blocks, forming an amphiphilic structure that self-assembles into vesicles. This composite approach provides both the stability needed for vesicle formation and the safety benefits of replacing ethylene oxide with less hazardous materials

Inventive Principle:
Principle #40Composite materials

2Reliability

If ethylene oxide-based copolymers are used, then vesicles can be formed, but functionalization and cross-linking become difficult

Engineering Contradiction:
Improvevesicle formationVSAvoidfunctionalization ease
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent introduces specific functional groups at localized positions within the copolymer structure, particularly at the block interfaces and chain ends. The oxazoline blocks provide specific functionalization sites that are more accessible and reactive than ethylene oxide, enabling easier post-polymerization modification while maintaining vesicle formation capability

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention changes the chemical parameters of the hydrophilic block from ethylene oxide to oxazoline derivatives, which have different reactivity profiles. The oxazoline rings contain nitrogen atoms with lone pairs that can serve as functionalization sites, and the polymerization conditions can be tuned to create end groups with specific reactivities, making the system more amenable to functionalization and cross-linking

Inventive Principle:
Principle #35Parameter changes

3Reliability

If conventional copolymers are used for vesicle formation, then basic vesicles are obtained, but control over vesicle size and permeability is limited

Engineering Contradiction:
Improvevesicle formationVSAvoidvesicle size control
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent employs dynamic control of vesicle formation by adjusting polymerization parameters such as monomer ratio, chain length, and block composition during synthesis. The living polymerization technique allows for precise control of block lengths and molecular weights, which directly influence vesicle size and permeability, enabling dynamic optimization for different applications

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention systematically varies key parameters including the ratio of hydrophilic to hydrophobic blocks, the molecular weight of each block, and the degree of polymerization. These parameter changes directly control the self-assembly process, allowing precise tuning of vesicle size, shape, and permeability properties to match specific delivery or filtration requirements

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

These block copolymers facilitate the formation of stable vesicles with controlled permeability, suitable for drug delivery and membrane applications, including targeted delivery and filtration, with enhanced resistance to detergents and improved handling characteristics.

Implementation Method 1

Vesicles formed from block copolymers... Amphiphilic block copolymers have been studied as a synthetic alternative for use in the production of artificial vesicles

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

the permeability of the block copolymers is inherently low, and can be adjusted to be very low, which makes the polymers valuable for a number of applications, including use in vesicles for delivery of substances

Methodology Applied
Scientific EffectPermeation: Permeation

Data Source

PatentEP3274396B1Vesicles formed from block copolymers, and novel block copolymers
Publication Date: 2023.04.05 VANDSTROM APS
  • EP3274396B1 patent drawingFigure 1A~2
  • EP3274396B1 patent drawingFigure 3~4
  • EP3274396B1 patent drawingFigure 5~6

AI summary

Vesicles formed from a block copolymer comprising at least one (poly)2-C1-3alkyl-2-oxazoline block and at least one polybutadiene block; and membranes comprising such vesicles. Block copolymers comprising at least one (poly)2-C1-3alkyl-2-oxazoline block and at least one polybutadiene block, provided that the copolymer is not the diblock copolymer consisting of 40 butadiene units and 190 2-methyl-2-oxazoline units terminated by a hydroxy group, are novel, and also form part of the invention.