Nanoporous Microsponge Particles via Organic Cross-Linking

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Solution Overview

Problem

Conventional methods for producing nanoporous microparticles for biomolecule delivery often involve toxic elements and harsh conditions, limiting their safety and efficiency as carriers for drugs and biomolecules.

Innovation Solution

A method involving cross-linking/precipitation of hyaluronic acid with a cross-linking agent prepared from 1,1'-carbonyldiimidazole and a diamine compound, producing nanoporous microsponge particles with a high swelling ratio suitable for drug delivery, characterized by an average molecular weight range of 10KDa to 200KDa, and specific dimensions and pore sizes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Shape

If inorganic components (metal salts) are added to produce nanoporous microparticles, then porous structure and high surface-to-volume ratio are achieved, but toxic elements and harsh conditions are introduced

Engineering Contradiction:
Improveporous structureVSAvoidtoxic elements
Core Design Contradiction:
ShapeVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and removes the harmful inorganic metal salt components from the nanoparticle synthesis process. Instead of using metal phosphates (calcium, manganese, copper) as structure-forming agents, the patent employs purely organic crosslinking agents that form hydrogen-bonded networks, eliminating toxic elements while preserving the desired porous microsponge architecture.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces organic crosslinking agents as intermediary substances that mediate the formation of nanoporous structures without introducing toxicity. These organic mediators (such as glutaraldehyde, genipin, or EDC/NHS couples) facilitate the crosslinking of polysaccharide chains to create the porous network, replacing the role of inorganic metal salts while being biocompatible and non-toxic.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If high molecular weight polysaccharides are used, then structural stability is improved, but swelling ratio decreases

Engineering Contradiction:
Improvestructural stabilityVSAvoidswelling ratio
Core Design Contradiction:
Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The invention optimizes the molecular weight parameter of the polysaccharide precursors to a specific range (10-200 KDa) that balances structural stability and swelling capacity. This parameter optimization ensures that the chains are long enough to form stable crosslinked networks but short enough to allow adequate water penetration and swelling, achieving both structural integrity and high drug loading capacity.

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 method enables the production of biocompatible nanoporous microsponge particles with high loading and sustained release capabilities for proteins and other biomolecules, enhancing their bioavailability and suitability for regenerative medicine and pharmaceutical applications without using toxic metal ions.

Implementation Method 1

a cross-linking/precipitation step wherein a cross-linking agent reacts with hyaluronic acid having nucleophile functional groups which react with said cross-linking agent

Methodology Applied
Scientific EffectCross-linking reaction: Chemical Bonding

Implementation Method 2

The swelling capability of nanoporous microsponge particles is a telling ex-post measurement of capillary suction of a nanoporous microsponge particle

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 3

said a cross-linking agent being prepared by a reaction between 1,1'-carbonyldiimidazole (CDI) and a diamine compound

Methodology Applied
Scientific EffectChemical reaction: Chemical Bonding

Implementation Method 4

a cross-linking/precipitation step wherein a cross-linking agent reacts with hyaluronic acid

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Data Source

PatentEP4143240B1Nanoporous microsponge particles (NMP) of biocompatible polymers as universal carriers for biomolecules delivery
Publication Date: 2023.09.20 NANOFABER SRL
  • EP4143240B1 patent drawingFigure 1
  • EP4143240B1 patent drawingFigure 2A~2D
  • EP4143240B1 patent drawingFigure 3

AI summary

A method to produce nanoporous microsponge particles useful as carriers for drug delivery. The method comprises a cross-linking/precipitation step wherein a cross-linking agent reacts with a biocompatible polymer having nucleophile functional groups, which react with said cross-linking agent. The cross-linking agent is prepared by a reaction between 1,1'-carbonyldiimidazole (CDI) and a diamine compound. The biocompatible polymer has an average molecular weight ranging from 10KDa to 150KDa.