Crosslinked Polyester Particles Sustained Drug Release

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Solution Overview

Problem

Current drug delivery particles face challenges in controlling particle size and morphology for reproducible results, limited drug loading capacity, rapid biodegradation, and a burst effect leading to inconsistent drug release profiles.

Innovation Solution

Development of crosslinked degradable particles with polyester backbones crosslinked via thioethers, allowing for controlled release of drugs through degradation, erosion, or diffusion, with specific methods involving functional groups, crosslinkers, and solvents to achieve uniform size and sustained drug release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If smaller particles are used to improve biodegradation rate, then drug release speed increases, but drug loading capacity decreases and sustained release duration is insufficient

Engineering Contradiction:
Improvedrug release speedVSAvoiddrug loading capacity
Core Design Contradiction:
SpeedVSQuantity of substance

Solution Approach 1:

The patent changes the chemical structure parameter of the particle matrix by incorporating hydrophobic segments and crosslinkable functional groups (allyl, propargyl, epoxide) into the polyester backbone. This structural modification enables the particles to maintain larger sizes with higher drug loading capacity while achieving controlled degradation rates through the hydrophobic effect and crosslinking density, resolving the contradiction between release speed and loading capacity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite particle structures by combining polyester backbones with crosslinking agents (dithiols, diamines, etc.) to form crosslinked networks. This composite approach allows the particles to achieve both high drug loading capacity (through larger size) and controlled release rates (through crosslinking density and hydrophobic segments), simultaneously satisfying both requirements.

Inventive Principle:
Principle #40Composite materials

2Duration of action of stationary object

If crosslinked particles are used to extend drug release duration, then sustained release is achieved, but particle size and morphology control becomes difficult

Engineering Contradiction:
Improvedrug release durationVSAvoidparticle size and morphology control
Core Design Contradiction:
Duration of action of stationary objectVSManufacturing precision

Solution Approach 1:

The patent incorporates crosslinkable functional groups (allyl, propargyl, epoxide) and crosslinking agents into the particle formulation before final particle formation. The crosslinking reaction is then triggered under controlled conditions (UV irradiation, thermal treatment, or chemical reaction) after particles are formed, allowing precise control of particle size and morphology during formation while subsequently achieving extended drug release through the crosslinked network structure.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If drug is dispersed in particles for delivery, then therapeutic effect is achieved, but burst effect occurs causing inconsistent drug release

Engineering Contradiction:
Improvetherapeutic effectVSAvoiddrug release consistency
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent creates local heterogeneity in the particle structure by incorporating hydrophobic segments and crosslinkable functional groups at specific locations within the polyester backbone. This local quality variation creates regions with different drug affinity and degradation rates, preventing the burst effect by ensuring uniform drug distribution and controlled release throughout the particle matrix, thereby achieving consistent therapeutic delivery.

Inventive Principle:
Principle #3Local quality

4Quantity of substance

If larger particles are used to increase drug loading capacity, then more drug can be loaded, but biodegradation rate decreases leading to insufficient release duration

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

Solution Approach 1:

The patent modifies the chemical composition parameters of the particle matrix by incorporating hydrophobic segments and crosslinkable functional groups into the polyester backbone. This structural change enables larger particles to maintain appropriate degradation rates through the hydrophobic effect (which slows water penetration) and controlled crosslinking density, allowing simultaneous achievement of high drug loading capacity and sufficient release duration.

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 crosslinked particles provide reproducible, sustained drug release over an extended period (up to several months) without a burst effect, ensuring consistent therapeutic delivery and improved biocompatibility.

Implementation Method 1

reacting the functional groups with crosslinkers to form a crosslinked degradable particle

Methodology Applied
Scientific EffectThioether crosslinking: Chemical Bonding

Implementation Method 2

The particles can release drug by degradation, erosion, diffusion, or a combination of mechanisms

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP4019575B1Crosslinked particles
Publication Date: 2023.12.06 LE DEVEDEC FRANTZ
  • EP4019575B1 patent drawingFigure 1A
  • EP4019575B1 patent drawingFigure 1B
  • EP4019575B1 patent drawingFigure 1C

AI summary

Disclosed are crosslinked particles (e.g., microparticles) that are capable of storing and releasing drugs. The particles can be macroparticles, microparticles, or nanoparticles and can be composed of polyester backbones. The particles can be loaded with a drug. The particles can degrade in vivo to release the drug. The particles can be prepared by crosslinking functionalized polyester backbones and loaded with a given drug. The particles of the present disclosure can be injected with a syringe. In some embodiments, the particles of the present disclosure are administered in connection with a surgery and release the drug after the site of the surgery for a period of 1-6 months.