Title
Scalable Production of Therapeutic Protein Nanoparticles Using Flash Nanoprecipitation
Author
Zhipeng Zeng, Cong Dong, Pengfei Zhao, Zhijia Liu, Lixin Liu, Hai‐Quan Mao, Kam W. Leong, Xiaohu Gao, Yongming Chen
Year
2018
Journal
Advanced Healthcare Materials
Abstract
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.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Nanostructures, Materials, Biochemistry