Zein Nanoparticle Size Control via pH-Adjusted Precipitation
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Solution Overview
Problem
Existing methods for forming nanoparticles from hydrophobic, water-insoluble proteins like zein result in larger particle sizes and wider distributions, leading to immunogenicity issues when used in vivo, as particles greater than 500 nm are prone to phagocytosis and recognized by immune cells.
Innovation Solution
A pH-controlled nanoprecipitation process using specific grades of proteins like zein, buffers, surfactants, and phospholipids to produce nanoparticles with controlled sizes between 100 nm to 400 nm, reducing immunogenicity by stabilizing the particles and preventing aggregation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional methods are used to form zein particles, then particle formation is achieved, but particle size is large (micron range) and distribution is wide
Solution Approach 1:
The patent applies parameter changes by controlling pH to be between 6.8 and 7.4 (near the isoelectric point of zein), using specific solvent compositions (hydroalcoholic solvents with 20-80% ethanol), and adjusting protein concentration (1-10% w/v) to achieve nanoparticle sizes of 100-400 nm with narrow distribution, resolving the contradiction between manufacturing precision and ease of manufacture
Solution Approach 2:
The patent utilizes phase transitions by inducing nanoprecipitation through pH adjustment and solvent composition changes, causing zein to transition from a dissolved state to a precipitated nanoparticle state, thereby achieving controlled nanoparticle formation without complex manufacturing steps
2Object-affected harmful factors
If particle size is reduced to avoid phagocytosis, then immunogenicity is reduced, but manufacturing control becomes more difficult
Solution Approach 1:
The patent changes multiple parameters simultaneously - pH (6.8-7.4), solvent composition (hydroalcoholic with specific ethanol percentages), and protein concentration (1-10% w/v) - to achieve the dual goal of producing nanoparticles smaller than 500 nm to avoid phagocytosis while maintaining narrow size distribution through controlled nanoprecipitation
Solution Approach 2:
The patent uses hydroalcoholic solvents as intermediaries to control the precipitation process, where the solvent composition acts as a mediator between the protein solution and the final nanoparticle structure, enabling precise control over particle size and distribution while maintaining immunogenicity reduction
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 achieves non-immunogenic nanoparticles with a narrow size distribution, enhancing their suitability for therapeutic and diagnostic applications by avoiding phagocytic uptake and providing sustained delivery of encapsulated molecules for up to a week.
Implementation Method 1
a pH-controlled nanoprecipitation process using specific grades of proteins like zein, buffers, surfactants, and phospholipids to produce nanoparticles with controlled sizes between 100 nm to 400 nm
Implementation Method 2
adding a buffering agent and a surfactant, PBS and the poloxamer Syperonic PE, to it to arrive at a pH between 6.8 and 7.4
Implementation Method 3
adding a buffering agent and a surfactant, PBS and the poloxamer Syperonic PE, to it to arrive at a pH between 6.8 and 7.4 after which it is processed to effect a reduction in diameter of particles within the solvent
Implementation Method 4
The non-immunogenic effect of the nanoparticles made in accordance with the methods of the present invention is achieved by controlling the size of the particle formed by the method, as well as the range of particle sizes
Data Source
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Figure 3a~4C
AI summary
Methods are described for producing non-immunogenic nanoparticles from protein sources by controlling the pH in a nanoprecipitation process. The nanoparticles that are produced by the disclosed methods range in diameter size from about 100 ran to about 400 nm, with a preferred diameter size of from approximately 100 nm to approximately 300 nm, thereby rendering them non- immunogenic. The invention further discloses methods for producing nanoconjugates that are suitable for a variety of therapeutic, diagnostic and other uses.