Intra-lymph node PLGA microparticles for immune tolerance induction

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Solution Overview

Problem

Therapeutic vaccination for autoimmune diseases, such as multiple sclerosis, faces challenges in directing immune responses and achieving local targeting of immune populations due to rapid in vivo clearance of hydrophobic drugs, limiting their effectiveness in inducing specific immune tolerance.

Innovation Solution

A method involving direct intra-lymph node administration of a composition comprising a myelin antigen and a biodegradable polymer, such as PLGA, along with an immunomodulatory agent like rapamycin, to induce immune tolerance without surface ligands for targeting, effectively reducing and reversing multiple sclerosis symptoms by promoting systemic antigen-specific tolerance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hydrophobic immunomodulatory drugs are administered systemically, then immune response modulation is achieved, but rapid in vivo clearance limits therapeutic effectiveness and duration

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoiddrug residence time

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent uses biodegradable polymer particles as intermediary carriers to deliver hydrophobic immunomodulatory drugs to lymph nodes. The polymer matrix protects the drug from rapid clearance and enables sustained release, while the particles themselves are taken up by lymph node-resident cells, serving as a mediator between the drug and the target immune cells.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical state and delivery parameters of the drug by formulating it within biodegradable polymer particles. This encapsulation alters the drug's pharmacokinetic properties, extending its residence time in the lymph node and enabling controlled release over days to weeks, thereby resolving the rapid clearance issue.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If systemic administration of immunomodulators is used, then broad immune modulation occurs, but inability to locally target specific immune populations reduces precision

Engineering Contradiction:

Improveimmune response directionalityVSAvoidtargeting precision

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by concentrating the immunomodulatory drug delivery specifically within lymph nodes rather than distributing it systemically. The biodegradable polymer particles are taken up by lymph node-resident dendritic cells and macrophages, creating a localized high-concentration effect precisely where antigen presentation and immune cell activation occur, thereby achieving both local targeting and specific immune population modulation.

Inventive Principle:

Principle #3Local quality

3Adaptability or versatility

If therapeutic vaccines are designed to induce specific immune tolerance, then autoimmune disease treatment is enabled, but challenging to direct the nature of immune response in particular populations

Engineering Contradiction:

Improveimmune response typeVSAvoidimmune response direction control

Core Design Contradiction:

Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent employs biodegradable polymer particles as intermediaries that are naturally taken up by antigen-presenting cells (dendritic cells and macrophages) within the lymph node. This intermediary mechanism directs the immune response toward tolerance induction by ensuring the immunomodulatory drug is delivered to and internalized by the specific cell populations responsible for regulating immune responses, making the process more controllable and less challenging.

Inventive Principle:

Principle #24Intermediary (Mediator)

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

This approach significantly reduces the severity of multiple sclerosis symptoms, including slowing or halting the progression of primary-progressive multiple sclerosis, as demonstrated in the Experimental Autoimmune Encephalomyelitis mouse model, with a single administration achieving systemic reduction in inflammation and prevention or delay of symptom onset.

Implementation Method 1

a biodegradable material such as a polymer

Methodology Applied

Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

an immunomodulatory agent like rapamycin, to induce immune tolerance

Methodology Applied

Scientific EffectImmunomodulation:

Data Source

PatentUS10071145B2Local engineering of the lymph node environment to promote immune tolerance

Publication Date: 2018.09.11 UNIV OF MARYLAND

AI summary

A method of inducing specific immune tolerance to myelin in an individual is provided. The method includes introducing directly into a lymph node of the individual an effective amount of a composition that contains a myelin antigen, a biodegradable material and at least one tolerogenic agent. The method is suitable for reducing the severity of symptoms of multiple sclerosis in individuals who suffer from primary-progressive multiple sclerosis (PPMS), and can halt or even reverse PPMS progression.