Processing and Scale-up of Polymeric Nanoparticles - Intracellular Delivery: Fundamentals and Applications - page 445

specific flow rates with each phase including the polymer solution and the non
solvent of the polymer. Simultaneously, the nanoparticle dispersion flows out of the
mixing device through the outlet. The mixing conditions provided by the mixing
device are constant whatever the volume of nanoparticle dispersion produced. This
can be achieved thanks to the small volume of each phase processed instanta-
neously and continuously in the mixing device. Therefore, the mixing device is the
central piece of the production set-up and allows to maintain homogenous starting
condition all along the addition of the two phases whatever the total volume is. This
first mixing device was designed on the basis of a T-shape tube (Briançon et al.
1999 ; Tewa-Tagne et al. 2007; Colombo et al. 2001 ; Galindo-Rodriguez et al.
2005 ). Several mixing devices have been designed since then by different groups
with capacities varying from a few microlitres to a few millilitres (Fig. 2 ) (Liu et al.
2008 ; Akbulut et al. 2009 ; Lince et al. 2009 ; Tuereli et al. 2009 ). Simulations of the
mixing dynamic flow occurring in the mixing device help optimizing operating
conditions of nanoprecipitation (Gavy et al. 2009 ; Lince et al. 2009 ). The whole
Fig. 2 Mixing devices used to produce large batches of nanoparticles by nanoprecipitation or
solvent displacement methods. ( a ) T shape mixing device according to Briançon et al. ( 1999 ),
diameters of the inlets can vary; ( b ) Smart mixer and reactor according to Lince et al. ( 2009 ),
diameters of the inlets can vary; ( c ) Vortex jet mixer according to Liu et al. ( 2008 ) and Akbulut
et al. ( 2009 ), the nanoparticle dispersion is evacuated from the center of the device; ( d ) Microjet
reactor set-up according to Tuereli et al. ( 2009 ). Black arrows indicate the inlet of the mixing
device feed with polymer solution, light gray arrows indicate the inlet of the mixing device feed
with the polymer non solvent and medium gray arrows indicate the outlet of the mixing device
where the nanoparticle dispersions are collected