Porous Embolization Microspheres Drug Loading via Organic Solvent

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Solution Overview

Problem

Current polymeric microspheres used in drug-eluting embolization techniques require pre-incubation with cytostatics, leading to inefficiencies such as high initial drug burst release, limited drug loading capacity, and safety concerns due to handling of pure cytostatics, and are ineffective for drugs with poor solubility in water.

Innovation Solution

A method involving porous polymeric microspheres loaded with therapeutic agents using an organic solvent, followed by washing and drying, which allows for higher drug loading capacity and controlled release, suitable for drugs with varying charges and poor aqueous solubility, enabling pre-loading for safer and more efficient embolization procedures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If porous polymeric microspheres are pre-incubated with cytostatics in aqueous media, then drug delivery to tumor is achieved, but drug loading capacity is limited and initial burst release occurs

Engineering Contradiction:
Improvedrug loading capacityVSAvoiddrug release profile
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the solvent parameter from aqueous to organic (alcohol-based), which fundamentally alters the drug-microsphere interaction. This parameter change enables higher drug loading capacity and controlled release by preventing premature drug dissolution and burst release that occurs in aqueous media.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces an organic solvent (alcohol) as an intermediary medium for drug loading. This intermediary enables the drug to be effectively loaded into the porous structure without direct aqueous contact, thereby controlling the release profile and preventing initial burst release while maintaining high loading capacity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If pure cytostatics are handled during pre-incubation, then drug loading is achieved, but safety concerns arise for practitioners

Engineering Contradiction:
Improvedrug loadingVSAvoidpractitioner safety
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The organic solvent acts as a safe intermediary that allows drug loading without requiring practitioners to handle pure cytostatics. The drug is delivered dissolved in the organic solvent, eliminating direct exposure to concentrated pure drug substances while achieving effective loading.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The drug is pre-dissolved in the organic solvent before contact with the microspheres. This preliminary action of dissolving the drug in a safe carrier reduces the harmful exposure risk during the loading process, as the drug is no longer in its pure, highly active form during handling.

Inventive Principle:
Principle #10Preliminary action

3Quantity of substance

If microspheres are swollen and impregnated with drug, then drug delivery is achieved, but high initial burst release occurs decreasing sustained release

Engineering Contradiction:
Improvedrug deliveryVSAvoidsustained release duration
Core Design Contradiction:
Quantity of substanceVSDuration of action of stationary object

Solution Approach 1:

The patent changes the physical state parameter of the drug-microsphere system by using organic solvent loading instead of aqueous impregnation. This prevents the drug from immediately dissolving and bursting out, thereby extending the sustained release duration while maintaining effective drug delivery.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent converts the potential harm of high initial burst release into a benefit by using the organic solvent to control the release kinetics. The solvent acts as a rate-limiting barrier that prevents excessive initial release, transforming what would be a harmful burst effect into a controlled, sustained release profile.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

4Ease of manufacture

If aqueous loading method is used, then simple procedure is achieved, but ineffective for drugs with poor water solubility

Engineering Contradiction:
Improveloading procedure simplicityVSAvoiddrug type compatibility
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The organic solvent-based loading method provides universal applicability across different drug types, particularly those with poor water solubility. The organic solvent serves as a universal medium that can dissolve and deliver a broader range of therapeutic agents, making the method adaptable to various drug characteristics while maintaining procedural simplicity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 achieves higher drug loading and controlled release, reducing the need for immediate drug handling by practitioners and enhancing therapeutic window duration, while being versatile for different drug types, including those poorly soluble in water.

Implementation Method 1

exposing porous polymeric microspheres to an organic solvent comprising a dissolved therapeutic agent thereby creating microspheres loaded with therapeutic agent

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

washing the microspheres loaded with therapeutic agent with water

Methodology Applied
Scientific EffectExtraction: Liquid-Liquid Extraction

Implementation Method 3

drying the washed microspheres

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP3755308B1Porous embolization microspheres comprising drugs
Publication Date: 2022.02.16 VAN RIJN BEHEER BV
  • EP3755308B1 patent drawingFigure 1A~1C
  • EP3755308B1 patent drawingFigure 2A~2D
  • EP3755308B1 patent drawingFigure 3A~3C

AI summary

The current invention provides a method of forming polymeric microspheres loaded with therapeutic agent, comprising: a. exposing porous polymeric microspheres to an organic solvent comprising a dissolved therapeutic agent thereby creating microspheres loaded with therapeutic agent, b. separating the microspheres loaded with therapeutic agent from the organic solvent, c. washing the microspheres loaded with therapeutic agent with water, and d. drying the washed microspheres. The microspheres are particularly useful in embolization therapy.