Anti-inflammatory Lipid Nanoparticles for Immune Response Mitigation

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Solution Overview

Problem

Current drug carriers like liposomes and lipid nanoparticles trigger an immunogenic response, leading to inflammatory reactions and limiting their therapeutic effectiveness due to their ability to activate the immune system, which increases the risk of anaphylactic shock and reduces their bioavailability.

Innovation Solution

Development of anti-inflammatory lipid nanoparticles comprising a lipid phase and at least one lipophilic anti-inflammatory agent, which are designed to minimize immune response by incorporating therapeutically effective amounts of lipophilic anti-inflammatory agents such as rofleponide or budesonide, and nucleic acid segments, thereby reducing inflammation and immune response markers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If liposome carriers are used for drug delivery, then targeted delivery to tissues and cells is improved, but immune system activation and inflammatory response increase

Engineering Contradiction:

Improvetargeted delivery effectivenessVSAvoidimmune system activation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent combines anti-inflammatory agents with lipid nanoparticle carriers to create a dual-function system that simultaneously delivers therapeutic cargo and suppresses immune activation. This merging of functions resolves the contradiction by integrating the harmful factor mitigation directly into the delivery vehicle.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The anti-inflammatory agents act as intermediaries between the lipid nanoparticle carrier and the immune system. These agents mediate the interaction by suppressing immune activation while allowing the carrier to perform its delivery function, thus resolving the contradiction between effective delivery and immune response.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If cationic lipid components are added to liposomes for enhanced cellular delivery, then delivery efficiency across cellular membrane is improved, but immune response and risk of anaphylactic shock increase

Engineering Contradiction:

Improvecellular delivery efficiencyVSAvoidimmune response

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts or removes the cationic lipid components that cause immune activation while retaining the essential drug delivery functionality. By eliminating the harmful cationic charge, the system maintains productivity without the associated immune response and anaphylactic shock risks.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the charge parameter of the lipid nanoparticles from positive (cationic) to neutral or negative, thereby altering the immune interaction profile. This parameter change maintains cellular delivery efficiency through alternative mechanisms while eliminating the harmful immune activation associated with cationic surfaces.

Inventive Principle:

Principle #35Parameter changes

3Duration of action of stationary object

If polyethylene glycol shield is added to LNPs to avoid recognition by mononuclear phagocyte system, then circulation time is improved, but immune response is only partially reduced

Engineering Contradiction:

Improvecirculation timeVSAvoidimmune response

Core Design Contradiction:

Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent creates composite lipid nanoparticle formulations that combine PEGylated lipids with anti-inflammatory agents. This composite structure provides both the circulation time extension from PEG shielding and the immune response suppression from anti-inflammatory components, resolving the partial effectiveness limitation.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The anti-inflammatory agents provide multi-functionality by simultaneously extending circulation time (through immune system suppression) and reducing immune response. This universal approach addresses both limitations of PEG shielding in a single integrated solution.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS11458106B2Lipid nanoparticles comprising lipophilic anti-inflammatory agents and methods of use thereof

Publication Date: 2022.10.04 ASTRAZENECA AB

AI summary

The immunostimulatory effect of lipid nanoparticles (LNPs) continues to block their use for safe and effective delivery of pharmaceutical drugs. Consequently, there exists a need to develop effective LNP delivery systems with an increased therapeutic window that do not trigger an inflammatory response. Disclosed herein are lipid nanoparticles comprising a lipid phase and at least one lipophilic anti-inflammatory agent, and pharmaceutical compositions comprising lipid nanoparticles and methods for using lipid nanoparticles. The anti-inflammatory lipid nanoparticles disclosed herein may further serve as platforms for selective delivery of, for example, nucleic acid segments to target cells and tissues, such as antisense oligonucleotides, DNA, mRNAs, siRNAs, Cas9-guideRNA complex.