Multi-Droplet Encapsulation by Extrusion Without Sonication
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Solution Overview
Problem
Conventional microparticle formulation techniques face challenges in encapsulating heat-sensitive drugs and live microorganisms due to the use of sonication, which generates excessive heat, and lack the ability to incorporate live cells in a single-step process.
Innovation Solution
The SMART method combines extrusion-based printing with emulsion evaporation, using shear force from a syringe nozzle to create micro- and nano-sized droplets without sonication, allowing for the encapsulation of heat-sensitive drugs and live microorganisms, including live cells, in a one-step process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If sonication is used for emulsion formation, then microparticles can be formed effectively, but excessive heat is generated that damages heat-sensitive drugs and live microorganisms
Solution Approach 1:
The patent removes the sonication step from the emulsion formation process, extracting the harmful heat-generating mechanism while retaining the core function of creating microdroplets through alternative means (mechanical mixing or extrusion), thereby protecting heat-sensitive encapsulated materials
Solution Approach 2:
The patent replaces the acoustic energy-based sonication mechanism with a mechanical mixing or extrusion-based droplet generation system, substituting a harmful physical field (ultrasound) with a controlled mechanical process that does not generate excessive heat
2Reliability
If conventional multi-step processes are used for microparticle formulation, then encapsulation can be achieved, but the process complexity increases and live cells cannot be incorporated
Solution Approach 1:
The patent combines multiple separate operations (emulsion formation, droplet generation, and encapsulation) into a single integrated extrusion-based printing process, where all steps occur simultaneously in one operation, reducing process complexity while maintaining encapsulation effectiveness
Solution Approach 2:
The patent performs preliminary preparation of the emulsion composition before the extrusion process, allowing the system to be pre-configured with all necessary components (polymer, drug, live cells, surfactant) so that the actual fabrication requires only a single extrusion step without intermediate manipulations
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 efficient encapsulation of heat-sensitive drugs and live microorganisms, such as bacteria and yeasts, while maintaining the integrity of temperature-sensitive components, and facilitates the incorporation of live cells, enhancing the versatility of drug delivery systems for various therapeutic applications.
Implementation Method 1
The secondary emulsion is then transferred into a syringe for the Cellink BioX bioprinter, and the shear stress exerted by the syringe nozzle is employed to generate micro-sized emulsion droplets.
Implementation Method 2
The deposited droplets are then deposited onto a pre-cooled cryogenic surface, leading to their ultra-rapid freezing in the form of frozen particles. This process allows for the evaporation of the organic solvent.
Data Source
AI summary
Described are techniques, systems, and methods include those employing pneumatic, pressure assisted, extrusion-based 3D printing and emulsion evaporation, emulsion diffusion, nanoprecipitation, desolvation, gelation, spray-based atomization, etc. for fabricating loaded microparticles or nanoparticles that encapsulate an active pharmaceutical ingredient or live cells into a biocompatible polymer or pharmaceutical excipients. The techniques provide for encapsulation of a variety of substances including proteins, plasmid DNA, lipophilic pharmaceutical compositions, hydrophilic pharmaceutical compositions, live cells, and/or cellular components into polymeric microparticles or nanoparticles. The particles loaded with active pharmaceutical ingredients can be used for the treatment of different diseases or conditions. The particles loaded with live cells can be used for disease treatment, but can also be used for securely storing the live cells in a stable condition for transport and later use in inoculating fermentation systems, for example, to generate recombinant proteins.