PLGA Nanoparticles Sulfated Surface Charge Targeting

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Solution Overview

Problem

Current drug delivery methods face challenges in targeting specific cells or tissues due to the lack of effective targeting mechanisms, leading to suboptimal therapeutic outcomes and adverse effects, as many drugs fail to reach their intended sites and antibodies used for targeting are prone to degradation and are costly to develop.

Innovation Solution

The development of microparticles and nanoparticles with high negative surface charges using sulfated polysaccharides and PLGA, which are stable and maintain their charge even after washing, allowing for enhanced targeting and therapeutic delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If antibodies are used for targeting cells, then targeting capability is improved, but stability and cost are worsened due to hydrolysis, degradation, and high production costs

Engineering Contradiction:
Improvetargeting capabilityVSAvoidstability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent replaces expensive and unstable antibodies with inexpensive polysorbate 80 molecules that can be easily synthesized and do not degrade. The surfactant provides comparable targeting functionality through its amphiphilic structure, with the hydrophobic tail inserting into cell membranes and the hydrophilic head remaining in aqueous environment, enabling cell penetration without the stability issues of antibodies

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent modifies the surface properties of nanoparticles by conjugating polysorbate 80, changing the physical-chemical parameters such as surface charge, hydrophobicity, and molecular structure. This parameter change enables the nanoparticle to achieve cell penetration and targeting capabilities similar to antibody-conjugated particles but with improved stability and reduced cost

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If drugs are administered systemically, then broad coverage is achieved, but targeting efficiency is worsened as only a small fraction reaches tumor sites

Engineering Contradiction:
Improvedrug distributionVSAvoidtargeting efficiency
Core Design Contradiction:
Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by conjugating polysorbate 80 specifically to the surface of nanoparticles, creating a localized functional layer that provides targeting capability. The surfactant molecules are positioned at the nanoparticle surface where their amphiphilic structure enables interaction with cell membranes, providing targeted delivery to tumor sites while maintaining systemic administration for broad distribution

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent creates a composite material system consisting of the drug-loaded nanoparticle core combined with a polysorbate 80 surface layer. This composite structure integrates the drug delivery function of the nanoparticle with the cell-penetrating and targeting function of the surfactant, achieving both broad distribution and high targeting efficiency

Inventive Principle:
Principle #40Composite materials

3Adaptability or versatility

If antibodies are conjugated to drug-loaded nanoparticles, then targeting is improved, but complexity and cost are worsened

Engineering Contradiction:
Improvetargeting capabilityVSAvoidproduction complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent replaces complex antibody conjugation processes with simple surfactant attachment. Polysorbate 80 can be conjugated to nanoparticle surfaces through straightforward chemical or physical methods, eliminating the need for complex protein chemistry, purification steps, and specialized facilities required for antibody conjugation, thereby significantly reducing production complexity and cost

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent uses polysorbate 80 as a simplified copy or analog of antibody functionality. Instead of using the complex protein structure of antibodies, the surfactant replicates the essential cell-penetrating and targeting functions through its smaller, simpler amphiphilic molecular structure, reducing manufacturing complexity while maintaining therapeutic efficacy

Inventive Principle:
Principle #26Copying

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 use of sulfated polysaccharides in PLGA particles creates a stable negative surface charge, improving targeting capabilities and therapeutic efficacy while reducing adverse effects and production costs.

Implementation Method 1

The microparticles and/or nanoparticles preferably comprise poly(lactic-co-glycolic acid) (PLGA), a sulfated polymer, such as a sulfated polysaccharides... the sulfated polymer is also referred to herein as 'an anionic polymer' or 'negatively charged agent'... impart a negative zeta potential having an absolute value of at least 25 mV

Methodology Applied
Scientific EffectElectrostatic charge: Electrostatics

Implementation Method 2

emulsifying the polymer solution in a solution of a second solvent to form an emulsion, wherein the first solvent is not miscible or partially miscible with the second solvent

Methodology Applied
Scientific EffectEmulsion: Emulsion

Implementation Method 3

removing the first solvent to form said microparticles or nanoparticles having negative surface charges

Methodology Applied
Scientific EffectPhase separation: Phase Change

Data Source

PatentUS12070508B2Microparticles and nanoparticles having sulfate groups on the surface
Publication Date: 2024.08.27 CYTODIGM INC

AI summary

This invention provides polymer particles which contain negative charges on the surface of the particle. Preferably, the particles comprise PLGA and sulfate polymer. The invention also provides polymer particle produced by the methods of the invention.