Nanocapsule Stability via Cationic Lipid Mediator Layer

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Solution Overview

Problem

Existing nanocapsules with negatively charged alginate outer layers and negatively charged supported lipid bilayers face issues with agglomeration and uncontrolled release of active moieties, leading to instability and leakage, which limits their therapeutic and pharmaceutical applications.

Innovation Solution

A method involving the formation of a supported lipid bilayer on porous silica nanoparticles with specific ζ-potential, incorporating DOTAP and other lipids through ultra-sonication, followed by the addition of sodium alginate and cross-linking to create a stable, biodegradable outer layer that prevents leakage and enables controlled release of active moieties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If negatively charged alginate is used as the outer layer of nanocapsules surrounded by negatively charged supported lipid bilayer, then biocompatibility and biodegradability are improved, but agglomeration and leakage occur leading to uncontrolled release

Engineering Contradiction:

ImprovebiocompatibilityVSAvoidstability

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

A cationic lipid layer (DOTAP) is introduced as an intermediary between the negatively charged supported lipid bilayer and the negatively charged alginate outer layer. This cationic layer acts as a mediator that electrostatically binds to both components, preventing direct negative-negative interaction that causes agglomeration, while maintaining biocompatibility and enabling controlled release

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If negatively charged alginate is used as the outer layer, then biodegradability is improved, but leakage and uncontrolled release of active moiety occur

Engineering Contradiction:

ImprovebiodegradabilityVSAvoidcontrol of release

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The cationic DOTAP lipid layer serves as a stabilizing intermediary that controls the interaction between the alginate outer layer and the inner negatively charged supported lipid bilayer. This intermediary layer regulates the release kinetics, preventing uncontrolled leakage while preserving the biodegradable nature of alginate

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The nanocapsule employs a composite structure with multiple layers: an inner negatively charged supported lipid bilayer, a cationic DOTAP lipid layer, and an outer negatively charged alginate layer. This composite architecture combines materials with complementary properties to achieve both biodegradability and controlled release

Inventive Principle:

Principle #40Composite materials

3Ease of manufacture

If supported lipid bilayer with negative charge is used, then encapsulation structure is formed, but agglomeration issues occur when combining with negatively charged alginate

Engineering Contradiction:

Improveencapsulation structure formationVSAvoidhomogeneity of outer layer

Core Design Contradiction:

Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The cationic DOTAP lipid layer acts as a intermediary that enables homogeneous distribution of the alginate outer layer by providing electrostatic binding sites that prevent agglomeration, while maintaining the integrity of the encapsulation structure

Inventive Principle:

Principle #24Intermediary (Mediator)

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 method enhances the stability and controlled release of active moieties, reducing leakage and agglomeration, making the nanocapsules suitable for various therapeutic, pharmaceutical, and cosmetic applications, including oral, topical, and loco-regional administration.

Implementation Method 1

supported lipid bilayer on a charged porous silica nanoparticle with a ζ-potential comprised between −10 mV and +10 mV

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

incorporating DOTAP and other lipids through ultra-sonication

Methodology Applied

Scientific EffectUltrasonic vibration: Ultrasonic Vibration

Implementation Method 3

addition of sodium alginate and cross-linking to create a stable, biodegradable outer layer

Methodology Applied

Scientific EffectCross-linking: Chemical Bonding

Data Source

PatentUS11406604B2Nanocapsules and method for manufacturing thereof

Publication Date: 2022.08.09 LUXEMBOURG INSTITUTE OF SCIENCE AND TECHNOLOGY (LIST)

AI summary

A method for manufacturing supported lipid bilayer on a porous silica nanoparticle with a ζ-potential comprised between −10 mV and +10 mV, the method comprising the steps of (a) providing a negatively charged supported lipid bilayer on a porous silica nanoparticle, wherein the negatively charged supported lipid bilayer has a ζ-potential inferior to −15 mV and wherein the negatively charged supported lipid bilayer comprised at least one phospholipid and; (b) adding a formulation of lipids, the lipids being 1,2-dioleoyl-3-trimethylammonium-propane alias DOTAP, cholesterol and at least one lipid different from DOTAP and cholesterol. The method further comprises the step of (c) performing an ultra-sonication for promoting DOTAP incorporation. The method can be supplemented by the step of addition of alginate and the step of cross-linking the alginate. Also a nanocapsule and composition comprising the nanocapsule.