Fabrication of protein-encapsulating microgels
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Publication Number
US-12350374-B2
Publication Date
2025-07-08
Expiration Date
Abstract
The present invention provides methods for fabricating protein-encapsulating microgels using hydrocarbon-in-fluorocarbon emulsions. The non-aqueous emulsion-based microgel fabrication methods can be used for the encapsulation of a wide range of proteins and peptides, including antibodies and antibody-fusion proteins, for therapeutic use with ease of administration.
Core Innovation
The invention relates to producing microparticles that include VEGF-Trap protein by fabricating a non-aqueous emulsion using dichloromethane and perfluorotripentylamine. A dispersed phase suspension is formed by combining polyethylene glycol-amine polymer, polyethylene glycol-N-hydroxysuccinimide polymer, a PEG polymer, and a powder including a VEGF-Trap protein with dichloromethane, and the dispersed phase suspension is added to a continuous phase solution containing perfluorotripentylamine and PFPE-PEG-PFPE.
Blending forces are applied to form a non-aqueous emulsion having multiple dichloromethane droplets that include the polyethylene glycol-amine polymer, the polyethylene glycol-N-hydroxysuccinimide polymer, and the powder including VEGF-Trap in the perfluorotripentylamine. After emulsion formation, dichloromethane and perfluorotripentylamine are removed from the non-aqueous emulsion to form isolated microparticles.
In the disclosed embodiments, the microgels/microparticles include a microgel cortex formed from crosslinked PEG, while VEGF-Trap protein is encapsulated within micronized protein cores. The formulation framework includes a fluorocarbon continuous phase and fluorosurfactants such as PFPE-PEG-PFPE (Pico-Surf 1), and the microparticles can be used as sustained-release microparticles.
Claims Coverage
The document provides one independent claim that covers a non-aqueous emulsion method to produce VEGF-Trap protein-containing microparticles using dichloromethane, perfluorotripentylamine, PEG-amine and PEG-N-hydroxysuccinimide polymers, and PFPE-PEG-PFPE as part of the continuous phase. Dependent claims refine the core method with specific ingredient identity and quantitative constraints on composition and resulting particle size.
Non-aqueous emulsion microparticle production with dichloromethane and perfluorotripentylamine
Combining polyethylene glycol-amine polymer, polyethylene glycol-N-hydroxysuccinimide polymer, a polyethylene glycol (PEG) polymer, and a powder including a vascular endothelial growth factor-Trap (VEGF-Trap) protein with dichloromethane to form a dispersed phase suspension; adding the dispersed phase suspension to a continuous phase solution including perfluorotripentylamine and PFPE-PEG-PFPE to form a combined dispersed phase suspension and continuous phase solution; applying blending forces to form a non-aqueous emulsion having multiple dichloromethane droplets including the polyethylene glycol polymers and the VEGF-Trap in the perfluorotripentylamine; and removing the dichloromethane and the perfluorotripentylamine to form isolated microparticles.
VEGF-Trap powder loading in dispersed phase
The concentration of the powder including a VEGF-Trap protein in the dispersed phase suspension is between 1.0% and 30% w/v.
PFPE-PEG-PFPE concentration in continuous phase
The concentration of PFPE-PEG-PFPE in the continuous phase solution is between 0.1% and 5.0% w/v.
Amine to N-hydroxysuccinimide molar ratio
A molar ratio of the amine to N-hydroxysuccinimide is between 1:1 and 1:2.
Microparticle diameter range
The isolated microparticles have a diameter between 1 μm and 200 μm as measured by imaging analysis.
Truncated VEGF-Trap protein identity
The VEGF-Trap protein is a truncated form of VEGF-Trap protein.
Overall, the claims center on forming isolated VEGF-Trap protein-containing microparticles by producing a non-aqueous emulsion with dichloromethane droplets dispersed in a perfluorotripentylamine/PFPE-PEG-PFPE continuous phase, using PEG-amine and PEG-N-hydroxysuccinimide to provide the crosslinkable polymer system within the dispersed droplets. Dependent claims additionally constrain VEGF-Trap powder loading, PFPE-PEG-PFPE concentration, amine/N-hydroxysuccinimide molar ratio, resulting microparticle diameter, and specify that VEGF-Trap can be a truncated form.
Stated Advantages
Sustained release microparticles are disclosed.
Documented Applications
Sustained release use of the produced microparticles is disclosed.
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