Methyl Palmitate Protein Nanoparticles for Reversible MPS Evasion

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Solution Overview

Problem

Existing strategies for reducing nanoparticle uptake by the Mononuclear Phagocytic System (MPS) in the liver and spleen, such as PEGylation and Gadolinium Chloride administration, are either ineffective or toxic, and there is a need for a safer and more effective method to transiently inhibit macrophage phagocytic activity to enhance nanoparticle delivery to targeted tissues.

Innovation Solution

Nanoparticles comprising methyl palmitate (MP) and serum globular proteins, such as albumin, are designed to transiently and reversibly modulate the phagocytic function of Kupffer cells and macrophages, using a self-assembly method that does not require surfactants or cytotoxic substances.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PEGylation is used to reduce nanoparticle uptake by MPS, then nanoparticle stealth potential is improved, but immune cell antibodies are generated reducing effectiveness

Engineering Contradiction:

Improvenanoparticle stealth potentialVSAvoidimmune cell antibodies

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the surface chemistry parameter of nanoparticles by replacing PEGylation with a different molecular configuration that does not trigger immune responses. This parameter change maintains stealth properties while avoiding antibody generation, resolving the contradiction between reliability and harmful factors.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If Gadolinium Chloride is administered to reduce phagocytic ability of macrophages, then nanoparticle delivery is improved, but toxicity and immune cell depletion occur

Engineering Contradiction:

Improvenanoparticle deliveryVSAvoidtoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces an intermediary substance that temporarily and reversibly reduces macrophage phagocytic activity without the toxicity of Gadolinium Chloride. This intermediary achieves the desired nanoparticle delivery improvement while avoiding harmful effects, resolving the contradiction between reliability and harmful factors.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If nanoparticle stiffness is increased for lung delivery, then delivery to target tissue is improved, but circulation half-life is reduced due to macrophage recognition

Engineering Contradiction:

Improvedelivery to target tissueVSAvoidcirculation half-life

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent changes the physical parameter of nanoparticle stiffness to create an optimal balance between deformability for evading macrophage recognition (extending circulation half-life) and structural integrity for effective tissue delivery. This parameter optimization resolves the contradiction between delivery reliability and duration of action.

Inventive Principle:

Principle #35Parameter changes

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 nanoparticles effectively inhibit macrophage uptake of secondary administered nanoparticles, enhancing their delivery to pathological tissues by reducing liver accumulation and increasing circulation time, while being biocompatible and reversible, thus avoiding long-term immune suppression.

Implementation Method 1

Methodology Applied

Scientific EffectSelf-assembly: Self-Assembly

Data Source

PatentUS12569450B2Nanoparticles for medical and diagnostic applications

Publication Date: 2026.03.10 FOND INST ITAL DI TECH

AI summary

The present disclosure provides nanoparticles comprising methyl palmitate and at least one serumglobular protein and uses thereof.