Polymeric Micelle Nanoparticle Fat-Soluble Drug Encapsulation

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Solution Overview

Problem

The hydrophobic core of polymeric micelles used in drug delivery systems, composed of polylactic acid, faces challenges in efficiently encapsulating fat-soluble drugs due to their hydrophobic nature.

Innovation Solution

A molecular assembly is developed using an amphiphilic block polymer based on polysarcosine and polylactic acid, combined with a fatty acid triglyceride, which forms a hydrophobic core capable of efficiently encapsulating fat-soluble drugs, utilizing a specific molar ratio and structure to achieve stable dispersion and targeting of tumor sites.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a polymeric micelle with a hydrophobic core composed of polylactic acid is used, then the nanoparticle can be formed with a particle diameter of several tens of nanometers to several hundreds of nanometers, but the encapsulation efficiency of fat-soluble drugs is insufficient

Engineering Contradiction:
Improveencapsulation efficiency of fat-soluble drugsVSAvoidcompatibility with fat-soluble drugs
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines polylactic acid (hydrophobic polymer) with fatty acid triglyceride to create a composite hydrophobic core. This composite structure provides both the structural integrity of polylactic acid and the enhanced fat-soluble drug compatibility of fatty acid triglyceride, resolving the contradiction between nanoparticle formation and drug encapsulation efficiency

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent modifies the chemical composition parameters of the hydrophobic core by incorporating fatty acid triglyceride alongside polylactic acid. This parameter change alters the core's solubility characteristics and interfacial properties, enabling improved encapsulation of fat-soluble drugs while maintaining the nanoparticle's structural stability

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If the hydrophobic core is composed solely of polylactic acid, then the nanoparticle structure is simple and stable, but the encapsulation of fat-soluble drugs is inefficient

Engineering Contradiction:
Improveamount of fat-soluble drug encapsulatedVSAvoidcomposition complexity of hydrophobic core
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent creates a composite hydrophobic core using polylactic acid and fatty acid triglyceride. This composite approach increases the drug encapsulation capacity by leveraging the lipophilic properties of fatty acid triglyceride, while the overall structure remains a straightforward two-component system that does not excessively increase complexity

Inventive Principle:
Principle #40Composite materials

3Reliability

If an amphiphilic block polymer with polylactic acid hydrophobic block and polysarcosine hydrophilic block is used, then the nanoparticle exhibits high retentivity in blood and reduced liver accumulation, but the encapsulation efficiency of fat-soluble drugs remains limited

Engineering Contradiction:
Improveblood retentivity and tumor targetingVSAvoidamount of fat-soluble drug encapsulated
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent modifies the hydrophobic core composition parameters by adding fatty acid triglyceride to the polylactic acid matrix. This parameter change enhances the core's ability to solubilize and encapsulate fat-soluble drugs without affecting the amphiphilic block polymer's self-assembly behavior, blood retentivity, or tumor targeting capabilities

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies local quality modification by specifically enhancing the hydrophobic core region with fatty acid triglyceride while maintaining the original amphiphilic block polymer structure. This localized modification improves drug encapsulation at the core without compromising the shell's blood compatibility and targeting functions

Inventive Principle:
Principle #3Local quality

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 enables effective encapsulation and targeted delivery of fat-soluble drugs to tumor sites, leveraging the Enhanced Permeability and Retention effect, thereby improving drug delivery efficacy.

Implementation Method 1

a linear amphiphilic block polymer having a polylactic acid chain as a hydrophobic block and a polysarcosine chain as a hydrophilic block self-assembles in an aqueous solution to form a polymeric micelle (lactosome)

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

a nanoparticle with a particle diameter of several tens of nanometers to several hundreds of nanometers retained in blood is likely to be accumulated in cancer (Enhanced Permeation and Retention (EPR) effect)

Methodology Applied
Scientific EffectEnhanced Permeability and Retention effect: Permeation

Data Source

PatentEP3517131B1Medicinal agent-containing molecular assembly which uses amphiphilic block polymer
Publication Date: 2023.07.12 SHIMADZU CORP
  • EP3517131B1 patent drawingFigure 1
  • EP3517131B1 patent drawingFigure 2~3
  • EP3517131B1 patent drawingFigure 4~5

AI summary

Provided is a molecular assembly (for example, a polymeric micelle nanoparticle) which is capable of efficiently encapsulating a fat-soluble drug. A molecular assembly comprising: an amphiphilic block polymer A1 comprising a hydrophilic block having a sarcosine unit and a hydrophobic block having a lactic acid unit; a hydrophobic polymer A2 having a lactic acid unit; a fatty acid triglyceride; and a fat-soluble drug. Examples of the fat-soluble drug include miriplatin.