Two-Step Crosslinking for Polymeric Microparticle Strength

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Solution Overview

Problem

Existing microcarriers used in cell culture and drug delivery technologies face challenges such as high manufacturing costs, reduced economic efficiency, and potential cell damage due to the need for proteolytic enzyme-based cell detachment processes. Additionally, biopolymers like hyaluronic acid are prone to degradation and exhibit reduced cell adhesion due to negative surface charges.

Innovation Solution

A method for preparing polymeric microparticles involves a two-step crosslinking process. First, a biocompatible polymer is crosslinked in an emulsion state with a first crosslinking agent, followed by extraction and secondary crosslinking in an organic solvent phase with a second crosslinking agent, optimizing crosslinking density and mechanical strength.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If a single crosslinking step is used to simplify the process, then manufacturing complexity is reduced, but mechanical strength and crosslinking efficiency are insufficient

Engineering Contradiction:
Improvecrosslinking process complexityVSAvoidmechanical strength of microparticles
Core Design Contradiction:
Device complexityVSStrength

Solution Approach 1:

The crosslinking process is divided into two distinct steps: first crosslinking in aqueous phase followed by second crosslinking in organic solvent phase. This segmentation allows each step to optimize for different requirements, achieving high mechanical strength without excessive process complexity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the solvent phase parameter between crosslinking steps (from aqueous to organic solvent) to optimize crosslinking efficiency and mechanical strength at each stage, resolving the contradiction between process simplicity and product performance

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If proteolytic enzymes are used for cell detachment to maintain cell viability, then cell damage is reduced, but manufacturing cost increases and economic efficiency decreases

Engineering Contradiction:
Improvecell damage during detachmentVSAvoidmanufacturing cost
Core Design Contradiction:
Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The microparticles are designed with temporary adhesion properties that allow easy detachment without expensive enzymes. The particles serve their purpose during culture and can be discarded or easily separated, eliminating the need for costly proteolytic enzymes while maintaining cell viability

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The microparticle surface is engineered to provide self-detachment capability through controlled adhesion mechanisms, eliminating the need for external enzymatic agents and reducing manufacturing costs while protecting cell integrity

Inventive Principle:
Principle #25Self-service

3Reliability

If hyaluronic acid is used as a biocompatible polymer to ensure biocompatibility, then biocompatibility is improved, but mechanical strength is insufficient and stability against degradation is reduced

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidmechanical strength
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The patent uses composite materials by combining hyaluronic acid with other polymers or crosslinking agents to maintain biocompatibility while significantly improving mechanical strength and degradation resistance of the microparticles

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

Crosslinking is performed preliminarily during the microparticle formation process, creating a pre-stabilized structure that maintains both biocompatibility and enhanced mechanical strength before cell culture or application

Inventive Principle:
Principle #10Preliminary action

4Strength

If crosslinking density is increased to improve mechanical strength, then strength is improved, but production yield decreases

Engineering Contradiction:
Improvemechanical strengthVSAvoidproduction yield
Core Design Contradiction:
StrengthVSProductivity

Solution Approach 1:

The patent optimizes crosslinking parameters including solvent type, crosslinking agent concentration, and reaction time to achieve high mechanical strength while maintaining acceptable production yield through parameter optimization rather than maximum crosslinking density

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 resulting polymeric microparticles exhibit enhanced mechanical strength, stability, and high crosslinking efficiency, while also improving production yield and maintaining biocompatibility, thus addressing the limitations of existing microcarriers.

Implementation Method 1

subjecting a mixture containing a biocompatible polymer in an emulsion state and a first crosslinking agent to a primary crosslinking reaction to form crosslinked particles; and extracting the crosslinked particles and performing a secondary crosslinking reaction in an organic solvent phase including a second crosslinking agent

Methodology Applied
Scientific EffectCrosslinking reaction: Chemical Bonding

Implementation Method 2

adding an aqueous solution in which the biocompatible polymer is dissolved to a hydrophobic solvent to form an emulsion

Methodology Applied
Scientific EffectEmulsion: Emulsion

Implementation Method 3

extracting the crosslinked particles and performing a secondary crosslinking reaction in an organic solvent phase

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Data Source

PatentEP3995530B1A method of preparing polymer microparticles, polymer microparticles, medical composition, cosmetic composition, medical articles, and cosmetic articles using the same
Publication Date: 2025.05.28 LG CHEM LTD

AI summary

The present disclosure relates to a method of preparing polymeric microparticles that can realize excellent mechanical strength and stability as well as high crosslinking efficiency and production yield, polymeric microparticles, medical compositions, cosmetic compositions, medical articles and cosmetic articles comprising the same.