Polymer-Nanoparticle Hydrogels for Co-Release of Varying-Size Cargos

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Solution Overview

Problem

Existing vaccine and immunotherapy delivery methods fail to provide sustained exposure of multiple compounds to the immune system, leading to inadequate immune responses due to inappropriate temporal control over antigen presentation and adjuvant activation, and challenges in co-releasing components of varying chemical nature.

Innovation Solution

A polymer-nanoparticle (PNP) hydrogel platform with dynamic non-covalent cross-links that encapsulates immunomodulatory cargos, allowing for simultaneous and sustained release of different compounds, creating a local inflammatory niche and enhancing immune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If subunit vaccines are administered as a single bolus injection, then the vaccine can be easily administered, but the antigen presentation duration is too short (1-2 days) to elicit robust immune responses

Engineering Contradiction:
Improveease of administrationVSAvoidantigen presentation duration
Core Design Contradiction:
Ease of operationVSDuration of action of moving object

Solution Approach 1:

The vaccine components (antigen and adjuvant) are pre-loaded into the hydrogel matrix before administration. The hydrogel is designed to degrade over time, releasing the antigen in a sustained manner that mimics the prolonged antigen presentation seen in natural infections, thereby eliminating the need for multiple booster shots

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the physical state and release kinetics of the antigen by embedding it in a degradable hydrogel matrix. This transforms the rapid bolus delivery into a controlled, sustained release system where the antigen concentration decreases gradually over days to weeks, matching the optimal immune stimulation profile

Inventive Principle:
Principle #35Parameter changes

2Reliability

If multiple immunomodulatory compounds are co-administered to enhance immune response, then the immune response can be strengthened, but the components with different chemical natures and molecular weights cannot be co-released at appropriate ratios

Engineering Contradiction:
Improveimmune response efficacyVSAvoidco-release control complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Multiple immunomodulatory compounds (antigen, adjuvant, and other immunomodulators) are merged into a single hydrogel delivery system. The hydrogel matrix provides a common platform that accommodates compounds of varying sizes and chemical properties, releasing them simultaneously or in a coordinated manner based on the matrix degradation kinetics

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent uses a composite hydrogel system that can incorporate multiple types of immunomodulatory compounds. The hydrogel matrix itself acts as a composite material that facilitates the co-delivery of molecules with different chemical natures, maintaining appropriate local concentrations of each component to achieve synergistic immune activation

Inventive Principle:
Principle #40Composite materials

3Duration of action of moving object

If polymer microparticles are used for prolonged vaccine delivery, then the antigen can be released over an extended period, but the synthesis requires organic solvents that can denature biologic cargo

Engineering Contradiction:
Improveantigen release durationVSAvoidcargo denaturation
Core Design Contradiction:
Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical composition and synthesis methodology from organic solvent-based polymer microparticles to aqueous-based degradable hydrogels. This parameter change eliminates the need for organic solvents that could denature proteins and other biologic cargo, while still achieving prolonged antigen release through controlled matrix degradation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The hydrogel matrix is designed to be biodegradable and temporary, serving its purpose of sustained release and then naturally degrading in the body. This disposable approach eliminates the need for complex removal procedures and avoids the toxicity issues associated with persistent polymer microparticles

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

4Reliability

If multiple shots are administered to achieve appropriate immune responses, then the immune response can be optimized, but the frequency of injections increases and complicates the treatment regimen

Engineering Contradiction:
Improveimmune response optimizationVSAvoidtreatment time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The hydrogel provides continuous antigen release over an extended period (days to weeks), maintaining a sustained immune stimulus that replaces the need for multiple discrete booster shots. This continuous action ensures that the immune system remains engaged with the antigen throughout the critical window for immune memory formation

Inventive Principle:
Principle #20Continuity of useful action

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 PNP hydrogel enhances humoral immune responses by prolonging germinal center activity, promoting high-affinity antibody production and memory, and providing a robust immune response with a single administration.

Implementation Method 1

A polymer-nanoparticle (PNP) hydrogel platform with dynamic non-covalent cross-links that encapsulates immunomodulatory cargos

Methodology Applied
Scientific EffectNon-covalent cross-links: Chemical Bonding

Implementation Method 2

creating a local inflammatory niche and enhancing immune responses

Methodology Applied
Scientific EffectInflammatory response:

Implementation Method 3

The PNP hydrogel enhances humoral immune responses by prolonging germinal center activity, promoting high-affinity antibody production and memory

Methodology Applied
Scientific EffectSustained release: Diffusion

Data Source

PatentEP3860613B1Injectable hydrogels for controlled release of immunomodulatory compounds
Publication Date: 2025.09.10 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • EP3860613B1 patent drawingFigure 1A~1B
  • EP3860613B1 patent drawingFigure 2A~2F
  • EP3860613B1 patent drawingFigure 3A~3D

AI summary

An immunomodulatory delivery system includes a hydrogel, a first immunomodulatory cargo encapsulated in the cargo, and a second immunomodulatory cargo encapsulated in the hydrogel. The hydrogel includes a polymer non-covalently crossed-linked with a plurality of nanoparticles. The first immunomodulatory cargo is smaller than the second immunomodulatory cargo. A ratio of a diffusivity of the first immunomodulatory cargo through the hydrogel to a diffusivity of the second immunomodulatory cargo through the hydrogel is less than 3.