Lipid Nanoparticle Formulations for Reduced Immune Response

Solution Overview

Problem

Lipid nanoparticle formulations used to deliver immunogenic or immunostimulatory cargoes often induce immune responses, leading to adverse side effects such as fever, chills, and liver damage, due to the immunogenic properties of certain lipids like cationic lipids and lipopolysaccharides.

Innovation Solution

Incorporating non-cationic lipids or lipid-conjugates, such as palmitoyl-oleoyl-phosphatidylglycerol (POPG) and dipalmitoylphosphatidylcholine (DPPC), into the formulations to reduce or eliminate the immune response by masking the immunogenicity of the cargo, thereby preventing immune activation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cationic lipids are used in lipid nanoparticle formulations to deliver immunogenic cargo, then delivery efficiency is improved, but immune response is activated leading to adverse side effects

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidimmune response

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces non-cationic lipids as intermediary substances that mediate between the cationic lipids (which provide delivery efficiency) and the immune system (which responds to cationic lipids). These non-cationic lipids form complexes with the cationic lipids to create a formulation that maintains delivery capability while reducing immune activation. The non-cationic lipids act as a buffer or shield that modulates the interaction between cationic lipids and immune cells.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite lipid formulation by combining cationic lipids with non-cationic lipids in specific ratios. This composite material integrates the beneficial properties of cationic lipids (efficient delivery) with the protective properties of non-cationic lipids (reduced immunogenicity). The composite formulation achieves a balance between delivery performance and immune compatibility through the synergistic combination of different lipid types.

Inventive Principle:

Principle #40Composite materials

2Reliability

If immunogenic or immunostimulatory cargoes are delivered using lipid formulations, then pharmacological efficacy is achieved, but immune activation causes serious side effects

Engineering Contradiction:

Improvepharmacological efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the potentially harmful immune-stimulating properties of the formulation into a beneficial outcome by using non-cationic lipids to modulate the immune response. Instead of completely suppressing immune activity, the formulation harnesses controlled immune modulation to enhance drug delivery while minimizing adverse effects. The immune system's response is redirected from a harmful reaction to a controlled, beneficial process that aids in the overall therapeutic effect.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes the chemical parameters of the lipid formulation by substituting cationic lipids with non-cationic lipids or adjusting the cationic-to-non-cationic lipid ratio. This parameter change alters the formulation's interaction with the immune system, reducing the activation of immune pathways while preserving the ability to deliver the pharmacological cargo effectively. The modified lipid composition achieves a new balance between efficacy and safety.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If cationic lipids are used to enhance cargo delivery, then target gene inhibitory activity is improved, but TLR-mediated immune responses are activated

Engineering Contradiction:

Improvetarget gene inhibitory activityVSAvoidTLR-mediated immune response

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces non-cationic lipids as intermediary substances that mediate between the cationic lipids (which provide delivery efficiency) and the immune system (which responds to cationic lipids). These non-cationic lipids form complexes with the cationic lipids to create a formulation that maintains delivery capability while reducing immune activation. The non-cationic lipids act as a buffer or shield that modulates the interaction between cationic lipids and immune cells.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of the lipid formulation by substituting cationic lipids with non-cationic lipids or adjusting the cationic-to-non-cationic lipid ratio. This parameter change alters the formulation's interaction with the immune system, reducing the activation of immune pathways while preserving the ability to deliver the pharmacological cargo effectively. The modified lipid composition achieves a new balance between efficacy and safety.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS9320798B2Lipid delivery formulations

Publication Date: 2016.04.26 NOVO NORDISK AS

AI summary

The invention provides formulations that contain an immunogenic or immunostimulatory cargo, delivery moiety and/or lipid, and a lipid that functions to reduce or prevent induction in a subject of an immune response which would otherwise occur when the immunogenic or immunostimulatory cargo, delivery moiety and/or lipid is administered to a subject as a component of an appropriate control formulation lacking the immune response reducing lipid. Specific immune response reducing lipids and uses thereof are further provided.