Lipid Nanoparticle Membrane Composition Stability
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Solution Overview
Problem
Lipid nanoparticle membranes in prior art face stability issues due to aggregation and rapid phagocytosis, with short-chain PEG increasing repellency but reducing stability, and long-chain PEG preventing phagocytosis but hindering target cell uptake.
Innovation Solution
A lipid nanoparticle membrane composition combining cationic lipids, neutral phospholipids, cholesterol, Tween, and a polyethylene glycol derivative in specific molar ratios, along with a method involving ethanol dilution and ultrafiltration, to enhance stability and circulation time while promoting targeted drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If short-chain PEG (Tween) is used alone in the lipid nanoparticle membrane, then the repellency between nanoparticles increases and aggregation is prevented, but the nanoparticle stability is reduced and it is easily phagocytosed by phagocytes
Solution Approach 1:
The patent combines two different PEG types (short-chain Tween and long-chain polyethylene glycol derivative) in the lipid nanoparticle membrane to create a composite structure that leverages the advantages of both: Tween provides aggregation prevention through electrostatic repulsion, while long-chain PEG provides steric hindrance against phagocytosis, achieving both stability and immune evasion
2Object-affected harmful factors
If long-chain PEG (TPGS) is used alone in the lipid nanoparticle membrane, then the recognition by phagocyte system is prevented and circulation time is prolonged, but the uptake by target tumor cells is hindered due to steric-hindrance effect
Solution Approach 1:
The patent creates local quality differentiation on the nanoparticle surface by using Tween (with its hydroxyl groups) to provide regions that can interact with target cells while long-chain PEG provides regions that prevent phagocytosis, allowing the nanoparticle to have different functional zones: one for immune evasion and another for cellular uptake
3Stability of the object's composition
If Tween is used in the lipid nanoparticle membrane, then aggregation is prevented, but the nanoparticle is easily lost in the systemic circulation
Solution Approach 1:
The patent merges the functions of two different PEG types by incorporating both Tween and long-chain polyethylene glycol derivative into the same lipid nanoparticle membrane, combining the aggregation-prevention function of Tween with the circulation-prolonging function of long-chain PEG to achieve both stability and extended circulation
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 composition significantly increases nanoparticle stability, prolongs circulation time, and enhances targeted delivery by combining short and long PEG chains, maintaining stability and effectiveness over 27 days.
Implementation Method 1
due to the lack of long-chain PEG embedded on the surface of nanoparticles, this nano-preparation is easily phagocytosed by phagocytes
Implementation Method 2
the short-chain PEG can increase the repellency between the nanoparticles to prevent the stability from being reduced due to their aggregation
Implementation Method 3
removing ethanol and free uncoated content in the mixed solution obtained in step (4) with an ultrafiltration or dialysis device
Data Source
Figure 1
AI summary
The present invention discloses a lipid nanoparticle membrane composition, and the membrane composition comprises a cationic lipid, a neutral phospholipid, cholesterol, Tween, and a polyethylene glycol derivative, with a molar ratio of (25-35):(40-50):(15-25):(1-5):(1-5) in the membrane composition. Also disclosed is a method for preparing a lipid nanoparticle from the lipid nanoparticle membrane composition. The present invention provides a lipid nanoparticle membrane composition that is capable of increasing the stability of the nanoparticle itself, thereby promoting the release of a medicament in tumor tissue and reducing the probability of being degraded