Hybrid Multi-Lamellar Nanostructure for EGF Delivery

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Solution Overview

Problem

Current methods for delivering epidermal growth factor (EGF) into the skin face challenges due to low skin absorption rates and loss of physiological activity during liposome preparation, primarily due to low encapsulation efficiency and denaturation of proteins under high pressure and temperature conditions.

Innovation Solution

A hybrid-type multi-lamellar nanostructure is formed through multivalent electrostatic and hydrophobic interactions between cationic lipid vesicles and EGF, allowing for high encapsulation efficiency and maintaining physiological activity by self-assembly at normal temperature and pressure, avoiding harsh conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If liposomes are prepared using high-pressure homogenization or Bangham method, then liposome formation is achieved, but physiologically active proteins are denatured and lose their characteristic physiological activity

Engineering Contradiction:
Improvephysiological activity of proteinVSAvoidliposome preparation process
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by pre-forming liposomes without proteins, then separately adding the physiologically active protein to the formed liposome structure. This avoids exposing the protein to denaturing conditions during liposome formation, thereby preserving its physiological activity while achieving successful encapsulation.

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If hydrophilic substances are encapsulated in the internal aqueous compartment of liposome, then encapsulation is achieved, but the encapsulation efficiency is low (10-20%)

Engineering Contradiction:
Improveamount of protein encapsulatedVSAvoidencapsulation efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent changes the physical and chemical parameters of the liposome structure by forming a multi-lamellar configuration with increased internal aqueous volume. This structural parameter change allows significantly higher amounts of hydrophilic protein to be encapsulated, improving encapsulation efficiency from the typical 10-20% to much higher levels.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If liposome structure is used for skin delivery, then biocompatibility and low toxicity are achieved, but skin absorption rate remains low

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidskin absorption rate
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent employs a nested doll strategy by creating multi-lamellar liposome structures where multiple aqueous compartments are nested within each other. This nested configuration increases the total internal volume available for protein encapsulation while maintaining the biocompatible liposome structure, thereby improving both capacity and skin delivery efficiency.

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

The novel nanostructure achieves high encapsulation efficiency and maintains EGF's physiological activity, enabling effective skin delivery with improved stability and permeation properties.

Implementation Method 1

multivalent electrostatic interactions in addition to hydrophobic interactions between empty vesicles formed of cationic lipid and anionic epidermal growth factor protein

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

multivalent electrostatic interactions in addition to hydrophobic interactions between empty vesicles formed of cationic lipid and anionic epidermal growth factor protein

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 3

a spontaneous self-assembly process occurring at normal temperature and normal pressure by mixing epidermal growth factor and empty vesicles formed of cationic lipid

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Data Source

PatentUS11712407B2Hybrid-type multi-lamellar nanostructure of epidermal growth factor and liposome and method for manufacturing same
Publication Date: 2023.08.01 CELLTRION INC
  • US11712407B2 patent drawing
  • US11712407B2 patent drawing
  • US11712407B2 patent drawing

AI summary

The present invention relates to a hybrid-type multi-lamellar nanostructure of an epidermal growth factor and a liposome and a method for manufacturing same. The new type of hybrid-type multi-lamellar nanostructure not only has a high epidermal growth factor encapsulating efficiency, but also can be manufactured through a simple process, such that the same can be easily delivered into a living body or a cell while maintaining a high physiological activity of the epidermal growth factor.