Inverse Precipitation for Biologic Encapsulation
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Solution Overview
Problem
Current methods for forming microparticles with biologics, such as proteins and peptides, face challenges in achieving high loading, controlled release, and uniformity due to limitations in existing water-in-oil-in-water emulsification processes, which often result in burst release and low loading capacities.
Innovation Solution
A method involving rapid, controlled precipitation to form nanoparticles with a hydrophilic core and amphiphilic copolymer shell, allowing for high loading and precise control of release rates by using amphiphilic copolymers to stabilize and aggregate nanoparticles into microparticles, eliminating the need for a matrix and enabling loadings up to 80 wt%.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If water-in-oil-in-water emulsification processes are used to form microparticles, then microparticles can be produced, but loading capacity is limited and burst release occurs
Solution Approach 1:
The patent changes the fundamental parameters of the encapsulation process by using reverse nanofprecipitation instead of emulsification, altering the phase separation mechanism and solvent system to achieve high loading capacity without burst release
Solution Approach 2:
The patent utilizes controlled phase transition through reverse nanofprecipitation, where the biologic transitions from soluble to precipitated state in a controlled manner, forming stable nanoparticles with high loading capacity and preventing burst release
2Quantity of substance
If high loading of biologic is achieved in microparticles, then more therapeutic agent is delivered, but release control becomes difficult and uniformity is lost
Solution Approach 1:
The patent segments the biologic loading process into controlled nanofprecipitation steps, forming individual nanoparticles with uniform characteristics that maintain release control even at high loading capacities
Solution Approach 2:
The patent changes the physical and chemical parameters of the precipitation process, including solvent composition, temperature, and mixing conditions, to achieve uniform nanoparticle formation with high biologic loading while maintaining controlled release profiles
3Quantity of substance
If rapid precipitation is used to form nanoparticles, then high loading capacity is achieved, but control over particle formation is reduced
Solution Approach 1:
The patent implements feedback control through monitored nanofprecipitation parameters, adjusting conditions in real-time to maintain both high loading capacity and precise control over nanoparticle formation
Solution Approach 2:
The patent optimizes multiple parameters including solvent composition, temperature, pH, and mixing rate to achieve rapid yet controlled precipitation, balancing high loading capacity with manufacturability
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
This approach enables the formation of microparticles with high loading capacities and controlled release profiles, overcoming the limitations of previous methods by providing stable, prolonged release of biologics without burst release, and allowing for precise control of release rates.
Implementation Method 1
Water soluble molecules—including peptides, proteins, DNA, RNA, non-biologic therapeutics, polysaccharide-based therapeutics (e.g., tobramycin) and imaging agents—precipitate into nanoparticles that are protected by a copolymer stabilizing agent. The particles thus made are colloidally stable in the first nonpolar solvent phase.
Implementation Method 2
A method involving rapid, controlled precipitation to form nanoparticles with a hydrophilic core and amphiphilic copolymer shell, allowing for high loading and precise control of release rates by using amphiphilic copolymers to stabilize and aggregate nanoparticles into microparticles
Implementation Method 3
A method of the invention for encapsulating water soluble molecules using rapid, controlled precipitation is presented.
Implementation Method 4
The particles thus made are colloidally stable in the first nonpolar solvent phase.
Data Source
AI summary
An “inverse” precipitation route to precipitate aqueous soluble species with copolymers as nanoparticles having a hydrophilic, polar core and a less polar shell is described. The aggregation of these nanoparticles to form larger microparticles and monoliths provides a highly loaded construct (e.g., a depot) for the sustained and controlled release of actives.