Continuous flow scalable production of injectable size-monodisperse nanoliposomes in easy-fabrication milli-fluidic reactors. (18th May 2021)

• Record Type: Journal Article
• Authors: Zizzari, Alessandra; Carbone, Luigi; Cesaria, Maura; Bianco, Monica; Perrone, Elisabetta; Rendina, Filippo; Arima, Valentina
• Is Part Of: Chemical engineering science. Volume 235(2021)
• Publication Date: 2021-05-18
• Subjects: Nanoliposomes -- Milli-reactors -- Coaxial flow -- Hydrodynamic flow focusing -- Continuous flow synthesis -- Viscosity-induced mixing; Chemical engineering -- Periodicals; Génie chimique -- Périodiques; Chemical engineering; Periodicals; Electronic journals; 660
• DOI: 10.1016/j.ces.2021.116481
• Languages: English
• ISSNs: 0009-2509

Abstract

Graphical abstract: Highlights: Cheap and easy-fabrication glass T-shaped and coaxial milli-reactors are reported. Unilamellar liposomes used in a known pharmaceutical product are synthesized. T-shaped milli-reactors improve production rates compared to microreactors. Coaxial milli-reactors also decrease size and polydispersity of liposomes. Efficient mixing at water–ethanol interfaces was promoted by viscosity contrasts. Abstract: The production of reproducible batches of liposomes suitable for parenteral administration is a time-consuming, multi-step process requiring extensive workable area. Microfluidic Hydrodynamic Focusing (MHF) chips allow one-pot synthesis of injectable size liposomes, although the use of low height-to-width aspect ratio (AR) microreactors limits the production rates. Herein, aiming at scaling up liposome production, while avoiding lithographic methods and clean room facilities, easy-fabrication glass MHF large channel (MHF-LC) chips of AR = 1, 3 with T-shaped and coaxial injection geometries are demonstrated. Narrowly distributed unilamellar nanoliposomes (unprecedented minimum average diameters 85 nm and polydispersity index of 0.13) with the formulation of a known pharmaceutical product (i.e., DOXIL®(CAELYX®)) are synthesized at production rates 15–20 times larger than T-MHF chips. The dependence of liposome size on the Reynolds numbers (in the range of 5–50) in the coaxial configuration is discussed as due to viscosity-induced mixing dynamics at the water–ethanol interface.