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Continuous flow scalable production of injectable size-monodisperse nanoliposomes in easy-fabrication milli-fluidic reactors
Chemical Engineering Science ( IF 4.7 ) Pub Date : 2021-02-02 , DOI: 10.1016/j.ces.2021.116481
Alessandra Zizzari , Luigi Carbone , Maura Cesaria , Monica Bianco , Elisabetta Perrone , Filippo Rendina , Valentina Arima

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.



中文翻译:

在易于制造的毫流反应器中连续流动可规模生产可注射的大小单分散纳米脂质体

适于肠胃外给药的可重制脂质体批次的生产是耗时的,多步骤的过程,需要广阔的工作区域。尽管使用低高宽比(AR)的微反应器会限制生产率,但微流体流体动力聚焦(MHF)芯片可以一锅合成大小可注射的脂质体。

在本文中,为了扩大脂质体的生产,同时避免了光刻方法和无尘室设施,展示了AR = 1、3的T形和同轴注射几何形状的易于制造的玻璃MHF大通道(MHF-LC)芯片。具有已知药物(例如DOXIL®(CAELYX®))配方的窄分布单层纳米脂质体(空前的最小平均直径为85 nm,多分散指数为0.13)比T-MHF芯片大15-20倍。讨论了在同轴构型中脂质体大小对雷诺数(在5-50范围内)的依赖性,这是由于在水-乙醇界面处粘度引起的混合动力学。

更新日期:2021-02-15
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