Cationic Microspheres for Anionic Drug Loading and Release

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Solution Overview

Problem

Current embolic microspheres for embolotherapy lack suitable properties for loading and delivering anionically charged drugs and imaging agents, with existing cationically charged microspheres exhibiting poor loading and release characteristics.

Innovation Solution

Development of cationic microspheres comprising a polymer obtained by crosslinking a macromer with a cationically charged vinylic co-monomer, featuring 1,2 or 1,3 diol groups and pendant cross-linkable groups, which are water-swellable but water-insoluble, allowing for improved drug and imaging agent loading and delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If existing cationically charged microspheres are used for loading anionically charged drugs, then drug loading is possible, but loading and release characteristics are poor

Engineering Contradiction:
Improvedrug loading capacityVSAvoidloading and release characteristics
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent modifies the chemical structure of the polymer by incorporating specific diol groups (1,2 or 1,3) and pendant cross-linkable groups, and by selecting specific cationically charged vinylic co-monomers with particular structural parameters (X being C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene). These parameter changes in the polymer structure improve both the loading capacity and the reliability of drug release characteristics simultaneously.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite polymer structure combining macromer with cationically charged vinylic co-monomer, forming a new material with enhanced properties. This composite approach allows the microsphere to achieve both high drug loading capacity and reliable controlled release characteristics that neither component alone could provide.

Inventive Principle:
Principle #40Composite materials

2Reliability

If gelatin-based cationic microspheres are used for embolization, then positive charge is achieved, but drug loading and release characteristics are poor

Engineering Contradiction:
Improvecharge stabilityVSAvoiddrug loading and release characteristics
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent replaces gelatin-based charge with synthetic polymer charge by incorporating cationically charged vinylic co-monomers with specific structural parameters. This parameter change in the charge-generating component maintains charge stability while dramatically improving drug loading and release characteristics through the polymer's controlled porosity and chemical structure.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention moves away from natural gelatin (which has limited controllability) to synthetic polymers that can be precisely engineered for optimal performance. This substitution allows for reproducible, reliable drug loading and release characteristics while maintaining the necessary cationic charge for anionic drug binding.

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

3Quantity of substance

If polymers with high drug loading capacity are used, then therapeutically useful quantities of drugs can be loaded, but delivery control and bioavailability are insufficient

Engineering Contradiction:
Improvetherapeutic drug loadingVSAvoiddelivery control and bioavailability
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent optimizes polymer parameters including molecular weight, degree of cross-linking, and co-monomer composition to achieve the right balance between drug loading capacity and controlled release. The specific structural parameters of the vinylic co-monomer and macromer are tuned to provide both high loading capacity and reliable delivery control with improved bioavailability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The polymer structure is designed with controlled porosity through the cross-linking of macromer with pendant groups. This porous structure allows high drug loading capacity while maintaining controlled release kinetics, as the pore size and distribution can be engineered to regulate drug diffusion and release rates, thereby improving delivery control and bioavailability.

Inventive Principle:
Principle #31Porous materials

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 cationic microspheres enable efficient loading and controlled release of anionically charged molecules, including drugs and imaging agents, with enhanced bioavailability and predictable embolization, reducing the risk of off-target emboli and improving treatment efficacy in hypervascular tumors.

Implementation Method 1

the polymer carries a charge at physiological pH, such that drugs carrying the opposite charge can be electrostatically bound to the polymer

Methodology Applied
Scientific EffectElectrostatic attraction: Electrostatics

Implementation Method 2

The polymer of the invention is water-swellable, but water insoluble; in the presence of aqueous liquid it will form a hydrogel

Methodology Applied
Scientific EffectHydrogel formation: Hydrogel

Data Source

PatentEP3344234B1Polymers and microspheres
Publication Date: 2021.11.24 BIOCOMPATIBLES UK LTD
  • EP3344234B1 patent drawingFigure 1
  • EP3344234B1 patent drawingFigure 2a~2d
  • EP3344234B1 patent drawingFigure 3

AI summary

New cationic polymers are provided that are suitable for the preparation of microspheres. The microspheres are capable of loading and eluting anionic species such as drugs and find use in i.a. embolotherapy