Nanolipidic Particle Assembly Size Control

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Solution Overview

Problem

Existing methods for delivering passenger molecules, such as pharmaceutical active ingredients, in lipid vesicles face limitations in achieving smaller vehicle sizes and improved encapsulation efficiency, which affects their effectiveness and stability.

Innovation Solution

A novel method utilizing a shelf-stable precursor solution to create nanolipidic particles (NLPs) and NLP assemblies with sizes ranging from 1 to 20 nanometers, allowing for the formation of smaller and more defined populations of carrier vehicles, including encapsulating carrier vehicles (ECVs) with enhanced encapsulation efficiency, by manipulating the precursor solution with a non-aqueous solvent before or after loading with passenger molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional lipid vesicle methods (SDMC) are used to deliver passenger molecules, then the vehicles can be formed with established procedures, but the vehicle size remains large (230-412 nanometers) and encapsulation efficiency is limited

Engineering Contradiction:
Improvevehicle size controlVSAvoidencapsulation efficiency
Core Design Contradiction:
Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent changes the concentration parameter of the precursor solution by diluting it with non-aqueous solvent to specific ranges (e.g., 0.1-10 mg/mL). This parameter change enables the formation of NLPs with controlled sizes (1-20 nm) and improves encapsulation efficiency, resolving the contradiction between size control and encapsulation capability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent segments the lipid assembly process into distinct stages: forming NLPs (1-20 nm) first, then allowing them to self-assemble into larger NLP assemblies (30-200 nm). This segmentation enables precise control over the size distribution and improves encapsulation efficiency by ensuring proper loading before assembly occurs

Inventive Principle:
Principle #1Segmentation

2Ease of manufacture

If the precursor solution concentration is high, then the vehicles form more readily, but the resulting particles are larger and less stable

Engineering Contradiction:
Improvevehicle formationVSAvoidparticle size stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent optimizes the precursor solution concentration parameter by diluting with non-aqueous solvent to specific ranges. This parameter change stabilizes the particle size composition, preventing uncontrolled aggregation while maintaining ease of formation through the defined dilution protocol

Inventive Principle:
Principle #35Parameter changes

3Length of moving object

If the vehicle size is reduced to improve delivery effectiveness, then the encapsulation capacity decreases, but the delivery precision improves

Engineering Contradiction:
Improvevehicle sizeVSAvoidencapsulation capacity
Core Design Contradiction:
Length of moving objectVSQuantity of substance

Solution Approach 1:

The patent segments the carrier system into two functional components: small NLPs (1-20 nm) that provide precise delivery and penetration capabilities, and larger NLP assemblies (30-200 nm) that provide enhanced encapsulation capacity. This segmentation allows the system to achieve both small effective size for delivery and sufficient total capacity for drug loading

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs a nested structure where multiple small NLPs are contained within or associate to form larger NLP assemblies. This nesting approach allows the outer assembly to provide capacity while the inner NLPs maintain small size for effective delivery, resolving the contradiction between size and capacity

Inventive Principle:
Principle #7Nested doll (Nesting)

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 results in improved encapsulation and delivery of passenger molecules, including vitamins, antibiotics, and other compounds, with increased stability and control over particle size, enabling targeted delivery and prolonged serum half-lives, as well as the ability to create optically clear solutions suitable for various applications.

Implementation Method 1

solubilizing an amphipathic material and a passenger molecule in a first quantity of a non-aqueous solvent

Methodology Applied
Scientific EffectSolubilization: Solvation

Implementation Method 2

a first quantity of water was added, forming a turbid suspension

Methodology Applied
Scientific EffectPhase separation: Phase Change

Implementation Method 3

a second quantity of non-aqueous solvent was added to form an optically clear solution

Methodology Applied
Scientific EffectSolubilization: Solvation

Implementation Method 4

organize the optically clear solution into SDMC vehicles by mixing with air or a second quantity of water

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Data Source

PatentUS9987234B2Nanolipidic particle assembly populations
Publication Date: 2018.06.05 NUVESSL INC

AI summary

Nanolipidic Particles (NLPs) having average mean diameters of 1 nm to 20 nm are made from a precursor solution. NLPs can be loaded with a desired passenger molecule. Assemblies of these particles, called NLP assemblies, result in a vehicle population of a desired size. Single application or multifunction NLP assemblies are made from the loaded NLPs and range in size from about 30 to about 200 nm. A method of using preloaded NLPs to make larger carrier vehicles or a mixed population provides increased encapsulation efficiency. NLPs have application in the cosmetics, pharmaceutical, and food and beverage industries.