Boronated Polymers for Acidic pH Drug Delivery

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Solution Overview

Problem

Existing drug delivery systems based on polymers with boronic acid groups are limited to basic pH conditions and cannot effectively deliver drugs at acidic pH levels, which are relevant in cellular transport processes such as in phagosomes and endosomes.

Innovation Solution

Development of boronated polymers with specific molecular structures that can form hydrogels and nanoparticles, capable of binding with glycoproteins and exhibiting enhanced transfection efficiency, allowing for reversible drug delivery triggered by pH, temperature, or carbohydrates, and showing improved endosomal escape properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If polymers with boronic acid groups are used for drug delivery, then the system can form hydrogels and interact with polyol systems, but the system is limited to basic pH conditions and cannot effectively deliver drugs at acidic pH levels

Engineering Contradiction:
ImprovepH range for drug deliveryVSAvoiddrug delivery effectiveness at acidic pH
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent modifies the chemical structure of boronic acid-containing polymers by introducing specific molecular structures (Formula I) that enable the polymer to maintain stability and functionality across a broader pH range, particularly at acidic pH levels where conventional boronic acid polymers fail. This structural parameter change allows the polymer to overcome the pH limitation while retaining its hydrogel-forming and drug delivery capabilities.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If conventional poly(amino ester)s are used for pH-triggered drug delivery, then the micro-particles can dissolve in acidic environments, but the system shows increased toxicity and limited transfection efficiency

Engineering Contradiction:
ImprovepH-triggered drug deliveryVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent creates a composite polymer structure combining boronic acid groups with specific molecular architectures (Formula I) that integrate the pH-responsive behavior of poly(amino ester)s with the enhanced stability and reduced toxicity of boronic acid-containing polymers. This composite structure achieves effective pH-triggered drug delivery while minimizing the harmful effects of toxicity and improving transfection efficiency.

Inventive Principle:
Principle #40Composite materials

3Duration of action of stationary object

If boronic acid-containing polymers are cross-linked to form hydrogels, then the system can provide controlled drug release, but the system cannot achieve reversible drug delivery at acidic pH conditions

Engineering Contradiction:
Improvecontrolled drug releaseVSAvoidreversible drug delivery capability
Core Design Contradiction:
Duration of action of stationary objectVSAdaptability or versatility

Solution Approach 1:

The patent introduces dynamic covalent chemistry through boronic acid ester bonds that can reversibly form and break down in response to pH changes. The specific molecular structure (Formula I) enables these bonds to remain stable at physiological pH for controlled drug release, while becoming reversible at acidic pH conditions, allowing the hydrogel to dynamically adapt its drug release behavior based on the environmental pH.

Inventive Principle:
Principle #15Dynamics

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 boronated polymers demonstrate lower toxicity, higher transfection efficiency, and the ability to form stable nanoparticles with enhanced endosomolytic properties, enabling effective drug delivery at acidic pH levels and providing controlled release mechanisms.

Implementation Method 1

boronic acid and boronic acids as well as polymers comprising boronic acid groups interact with polyol systems, e.g. polyvinyl alcohol, to form hydrogels

Methodology Applied
Scientific EffectHydrogel formation: Hydrogel

Implementation Method 2

In their cationic form, the poly(amino ester)s form complexes with DNA molecules or fragments thereof

Methodology Applied
Scientific EffectElectrostatic interaction: Ion Repulsion/Attraction

Implementation Method 3

Upon exposure to an acidic environment, e.g. the endosome or the phagosome of a cell, the micro-particles dissolve or disrupt due to an enhanced solubility of the poly(amino ester) which is caused by hydrolysis of ester bonds in the polymer backbone

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentEP2582741B1Boronated polymers
Publication Date: 2016.07.27 UNIVERSITY OF TWENTE
  • EP2582741B1 patent drawingFigure 1a
  • EP2582741B1 patent drawingFigure 1b
  • EP2582741B1 patent drawingFigure 1c

AI summary

The present invention relates to a boronated polymer according to Formula (1): a process for making the boronated polymer according to Formula (1), drug 10 delivery systems, aggregates, nanoparticles and hydrogels comprising the boronated polymer according to Formula (1).