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Scalable Production of Therapeutic Protein Nanoparticles Using Flash Nanoprecipitation
Author(s) -
Zeng Zhipeng,
Dong Cong,
Zhao Pengfei,
Liu Zhijia,
Liu Lixin,
Mao HaiQuan,
Leong Kam W.,
Gao Xiaohu,
Chen Yongming
Publication year - 2019
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201801010
Subject(s) - nanoparticle , materials science , nanotechnology , flash (photography) , bioavailability , solvent , chemistry , bioinformatics , organic chemistry , art , visual arts , biology
Flash nanoprecipitation (FNP) by fast mixing of drug‐containing organic solvent and water in a microchamber is a powerful and scalable technology to produce solid drug nanoparticles with high payload. The embedded therapeutic drugs, however, are largely limited to hydrophobic small molecules. By transferring proteins into organic solvent via hydrophobic ion pairing, the scope of FNP applications is expanded. This platform technology is capable of producing protein nanoparticles with tunable sizes (from ≈30 nm to sub‐micrometers), high‐production scale (grams per hour), high drug loading efficiency (>90%), and excellent reproducibility, opening a new paradigm for formulation of biological pharmaceuticals. As a proof‐of‐concept, insulin nanoparticles are made to address a major medical challenge; oral administration. A relative insulin bioavailability of 13.2% is achieved, enabling sustained reduction of blood glucose levels in a diabetic rat model.