Silicasome Synthesis Scale-Up for Uniform Mesoporous Nanocarriers
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Solution Overview
Problem
There is a lack of effective methods for scaled up synthesis of mesoporous silica nanoparticles (MSNPs) and lipid bilayer coated MSNPs (silicasomes) that meet pharmaceutical quality standards, as laboratory-scale synthesis protocols do not linearly scale to large-scale production, resulting in heterogeneous nanoparticle carriers.
Innovation Solution
A multi-parameter design method involving specific molar ratios of surfactant, triethanolamine, and tetraethylorthosilicate in water, followed by stirring and sonication to form mesoporous silica nanoparticles, which are then coated with a lipid bilayer to produce uniform silicasomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If laboratory-scale synthesis protocols are used, then nanoparticle quality and consistency are maintained, but production quantity is limited
Solution Approach 1:
The patent applies parameter changes by systematically adjusting multiple synthesis parameters (surfactant concentration, TEA amount, TEOS amount, water amount, stirring speed, reaction time, temperature) to optimize the balance between production quantity and nanoparticle consistency. The multi-parameter design allows scaling up while maintaining controlled nanoparticle formation through precise parameter management.
Solution Approach 2:
The patent implements dynamics by using adjustable stirring speeds (150-800 rpm) and reaction temperatures (25-99°C) that can be dynamically optimized during synthesis. The method allows real-time control of reaction conditions to maintain nanoparticle homogeneity while scaling up production volume.
2Productivity
If linear scaling of ingredients is applied, then production volume increases, but nanoparticle heterogeneity increases
Solution Approach 1:
The patent demonstrates that linear scaling of ingredients does not work by showing that nanoparticle synthesis requires non-linear adjustments of multiple parameters simultaneously. The method provides specific non-linear relationships between surfactant concentration, catalyst amount, precursor amount, and other parameters to maintain homogeneous nanoparticle formation at large scale.
Solution Approach 2:
The patent applies segmentation by dividing the synthesis process into distinct controllable steps: surfactant dissolution, catalyst addition, precursor addition, stirring, and reaction. This segmented approach allows independent optimization of each step to maintain nanoparticle homogeneity while scaling overall production volume.
3Productivity
If large batch sizes are synthesized, then production efficiency improves, but nanoparticle size distribution becomes broader
Solution Approach 1:
The patent uses parameter changes to control nanoparticle size distribution by optimizing stirring speed (150-800 rpm) and reaction temperature (25-99°C) ranges that maintain narrow size distributions even at large batch sizes. The method establishes specific parameter windows that prevent size broadening during scale-up.
Solution Approach 2:
The patent implements dynamics through adjustable stirring speeds and reaction conditions that can be optimized during synthesis to maintain consistent nanoparticle size distribution. The method allows real-time control to prevent size broadening while maintaining high production efficiency.
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 enables the production of large-scale MSNPs and silicasomes with consistent size distribution, high yield, and drug loading capacity, suitable for pharmaceutical use, enhancing cancer treatment efficacy and reducing toxicity.
Implementation Method 1
providing a surfactant in water at a concentration greater than the CTAC critical micellar concentration (CMC) of said surfactant to form a mixture comprising surfactant
Implementation Method 2
adding to said mixture tetraethylorthosilicate (TEOS); where the molar ratio of H2O:TEOS ranges from about 100:0.1 to about 100:1
Implementation Method 3
adding to said mixture triethanolamine (TEA); where the molar ratio of H2O:TEA ranges from about 100:0.02 to about 100:0.2
Implementation Method 4
stirring (or agitating) said mixture to allow said CTAC micelles, TEA, and TEOS to react
Implementation Method 5
followed by stirring and sonication to form mesoporous silica nanoparticles
Implementation Method 6
coated with a lipid bilayer to produce uniform silicasomes
Data Source
AI summary
In order to facilitate the approval and commercialization of silicasome drug delivery systems (e.g. irinotecan silicasomes) it is necessary to scale up synthesis of the drug-loaded silicasomes. In this regard, it was discovered that the synthesis protocols used for laboratory synthesis of drug-loaded silicasomes (e.g., 500 mg/batch) do not scale to large scale silicasome production, because the resulting products were too heterogeneous for use as pharmaceuticals. Accordingly, new methods are provided herein that effectively afford the large-scale production of mesoporous silica nanoparticles (MSNPs) and lipid bilayer coated MSNPs (silicasomes).