pH-Sensitive Hydrogel for High-Load Drug Delivery

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Solution Overview

Problem

Current drug delivery systems face challenges in carrying high-concentration drugs while maintaining the integrity and stability of molecular structure and biological activity, particularly for antibody drugs, due to the use of organic solvents which can inactivate proteins and disrupt drug stability during release.

Innovation Solution

A hydrogel composition comprising polyglutamic acid (PGA) with maleimide groups and polyethylene glycol (PEG) with thiol groups, forming a pH-sensitive cross-linked hydrogel system that encapsulates pharmaceutically active ingredients, enabling high drug loading and sustained release over extended periods without compromising the drug's integrity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If organic solvents are used in the preparation of drug delivery carriers, then the carrier can be formed, but the proteins are inactivated and the stability of drug molecular structure is compromised

Engineering Contradiction:
Improvecarrier preparationVSAvoiddrug stability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent changes the chemical parameters of the carrier preparation by using aqueous buffers (pH 4.0-6.5) instead of organic solvents. This parameter change allows the carrier to be formed while maintaining protein stability, as the aqueous environment prevents protein inactivation that occurs with organic solvents.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a composite hydrogel system combining polyglutamic acid with maleimide groups and polyethylene glycol with terminal thiol groups. This composite material achieves both carrier formation and drug stability through the synergistic interaction of the two polymers, eliminating the need for harmful organic solvents.

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If high-concentration drugs are loaded into the carrier, then the drug loading capacity is improved, but the integrity and biological activity of the drug may be compromised

Engineering Contradiction:
Improvedrug loading concentrationVSAvoiddrug integrity
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent optimizes the pH parameter of the hydrogel system to range from 4.0 to 6.5, which creates optimal conditions for both high drug loading and maintenance of drug integrity. This pH range prevents protein denaturation while allowing high concentration loading of antibody drugs.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The hydrogel acts as an intermediary matrix that protects the loaded drugs from degradation. The cross-linked hydrogel structure provides a protective environment that maintains drug integrity while enabling high loading concentrations, solving the contradiction between quantity and quality of drug delivery.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Duration of action of moving object

If the drug release period is extended, then the sustained release effect is improved, but the maintenance of molecular structure integrity and biological activity becomes more difficult

Engineering Contradiction:
Improvedrug release periodVSAvoidbiological activity
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The composite hydrogel system provides sustained release over extended periods (up to 35 days) while maintaining drug stability through the synergistic properties of PGA and PEG. The cross-linked structure controls release kinetics without compromising biological activity, resolving the contradiction between duration and reliability.

Inventive Principle:
Principle #40Composite 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 hydrogel system achieves high drug loading concentrations up to 300mg/mL and sustained release for over 35 days, maintaining the integrity and biological activity of encapsulated drugs, including antibodies and proteins, with controlled release profiles and extended half-life in vivo.

Implementation Method 1

polyglutamic acid (PGA) containing maleimide groups, and polyethylene glycol (PEG) containing terminal thiol groups

Methodology Applied
Scientific EffectCrosslinking reaction: Chemical Bonding

Implementation Method 2

the crosslinker will be cleaved in the mildly acidic conditions within the cell

Methodology Applied
Scientific EffectpH-sensitive cleavage: Hydrolysis

Data Source

PatentEP3311799B1Hydrogel compositions and drug delivery systems comprising the same
Publication Date: 2023.10.11 IND TECH RES INST
  • EP3311799B1 patent drawingFigure 1
  • EP3311799B1 patent drawingFigure 2
  • EP3311799B1 patent drawing

AI summary

A hydrogel composition is provided. The hydrogel composition includes polyglutamic acid (PGA) containing maleimide groups, and polyethylene glycol (PEG) containing terminal thiol groups, wherein the hydrogel composition has a pH value ranging from 4.0 to 6.5. A drug delivery system is also provided. The drug delivery system includes the above-mentioned hydrogel composition, and a pharmaceutically active ingredient encapsulated in the hydrogel composition.