The development of a microfluidic-based process is presented for the production ofnanomaterials in continuous-flow microreactors. A flow focusing configuration wasused enabling a controllable mixing process to assist the formation of thenanomaterials through precipitation, which was triggered by a solvent exchangeprocess. Initially, Pluronic® tri-block copolymers were used as model polymericbiomaterials, relating to drug delivery applications, to investigate the production ofempty polymeric micelles (PMs). Following the production of empty PMs, theproduction of copolymer stabilized organic ?-carotene nanopartilces (NPs) was alsoinvestigated. The formation of both PMs and NPs, within microfluidic reactors, wasfurther analysed by computational fluid dynamics (CFD) models in order to gain moreinsight into the nanoprecipitation process.It has been shown that, besides the important role played by the width of the focusedstream, the combined effect of reactor dimension, fluid properties, and flow conditionsignificantly influenced the mixing condition and therefore the nucleation and growthprocess. When low water soluble molecules were co-precipitated together withpolymeric stabilizer, competitive reactions resulted in the formation of two types ofNPs, i.e., either with or without loading drug. The obtained results were interpreted bytaking into consideration a new parameter representing the mismatching between theaggregations of the two precipitant species (polymer and drug), which played adecisive role in determining the size and polydispersity of the obtained NPs.Finally, the established microfluidic production procedure was examined from a drugdelivery point of view, by encapsulating a clinically relevant drug in PMs. PMscontaining mithramycin were prepared and tested in vitro as a therapeutic protocol forbeta-thalassemia.In conclusion, the results of this study had demonstrated that microfluidics couldfacilitate the production of nanostructures for drug delivery purposes, and offer anovel method to control their properties including particle size, size distribution andpharmaceutical efficacy.
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