Protein Nanoparticle Size Control via Zero-Length Crosslinking
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Solution Overview
Problem
Current methods for producing proteinaceous nanoparticles lack control over mean particle size and size distribution, which affects their in vivo uptake, biodistribution, and clearance, limiting their therapeutic and imaging applications.
Innovation Solution
A process involving zero-length crosslinkers at higher protein concentrations to form protein nanoparticles with closely defined mean particle sizes and narrow size distributions, using a single phase reaction in an aqueous medium without solvents or surfactants, allowing for controlled reaction conditions to achieve uniform particle properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional crosslinking methods are used at standard protein concentrations, then protein particles can be formed, but the mean particle size and size distribution cannot be closely controlled
Solution Approach 1:
The patent applies parameter changes by increasing the protein concentration to 8 mg/mL or greater and using zero-length crosslinkers at optimized concentrations to achieve precise control over mean particle size and size distribution. This systematic variation of reaction parameters enables manufacturing precision without excessive process complexity.
Solution Approach 2:
The patent employs feedback mechanisms through monitoring and controlling reaction conditions (pH, temperature, crosslinker concentration, protein concentration) to maintain optimal parameters throughout the crosslinking process, ensuring consistent particle size distribution and enabling precise particle size control.
2Reliability
If protein particles are made with closely defined sizes and narrow size distributions, then in vivo uptake and biodistribution improve, but the process requires higher protein concentrations and controlled reaction conditions
Solution Approach 1:
The patent uses parameter changes by implementing higher protein concentrations (8 mg/mL or greater) as a necessary condition to achieve the desired particle size control and narrow size distribution, which in turn improves in vivo performance including uptake and biodistribution characteristics.
3Manufacturing precision
If zero-length crosslinkers are used at higher protein concentrations, then protein nanoparticles with uniform properties are formed, but the reaction conditions must be precisely controlled
Solution Approach 1:
The patent implements feedback control by monitoring and adjusting reaction parameters including pH, temperature, crosslinker concentration, and protein concentration throughout the crosslinking process to maintain optimal conditions for forming uniform nanoparticles with precise size control.
Solution Approach 2:
The patent applies parameter changes through the systematic optimization of reaction conditions, specifically using zero-length crosslinkers at controlled concentrations with protein concentrations of 8 mg/mL or greater, enabling particle uniformity while managing reaction control requirements.
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 process enables the production of protein nanoparticles with precise size control, enhancing their uniformity and utility in medical imaging and therapeutic delivery by ensuring consistent properties and extended residence time in the body.
Implementation Method 1
produce protein particles comprising protein molecules that are covalently bonded together
Data Source
AI summary
Protein particles are prepared by causing or allowing protein molecules dispersed in a liquid medium at a concentration of 8 mg.mL−1 or greater to react in the presence of a zero-length crosslinker, so as to produce protein particles comprising protein molecules that are covalently bonded together. The protein particles may be produced with sizes in the sub-micron range with closely defined sizes and size distributions. The particles have applications in many fields, but are useful inter alia for the delivery of therapeutic agents and other agents, eg imaging contrast agents, to the body.