A hydrodynamic flow focusing microfluidic device for the continuous production of hexosomes based on docosahexaenoic acid monoglyceride

Cubosomes and hexosomes are emerging platforms for drug and nutraceutical delivery applications. In addition to common high- and low-energy batch emulsification methods for the preparation of these nano-self-assemblies, it is important to introduce suitable microfluidic devices with a precision control of the flow parameters for their continuous production. Microfluidics has several advantages including cost effectiveness, short-production time, and control of the nanoparticle size and size distribution. In the present study, a hydrodynamic flow focusing polyimide microfluidic device was employed for the continuous production of hexosomes based on docosahexaenoic acid monoglyceride (MAG-DHA), in the presence of the stabilizer Pluronic F127. The size, structural, morphological and size characterizations of the continuously produced MAG-DHA nanodispersions were investigated through an integrated approach involving synchrotron small angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy. We report on a simple process for the microfluidic synthesis of hexosomes with sizes ranging from 108 to 138 nm and relatively narrow size distributions as the polydispersity indices were in the range of 0.14-0.22. At the applied total volumetric flow rates (TFRs) ranging of 50-150 μL min