Formation of nanostructured biomaterials in lab-on-a-chip microsystems

The development of a microfluidic-based process is presented for the production of nanomaterials in continuous-flow microreactors. A flow focusing configuration was used enabling a controllable mixing process to assist the formation of the nanomaterials through precipitation, which was triggered by a solvent exchange process. Initially, Pluronic® tri-block copolymers were used as model polymeric biomaterials, relating to drug delivery applications, to investigate the production of empty polymeric micelles (PMs). Following the production of empty PMs, the production of copolymer stabilized organic ?-carotene nanopartilces (NPs) was also investigated. The formation of both PMs and NPs, within microfluidic reactors, was further analysed by computational fluid dynamics (CFD) models in order to gain more insight into the nanoprecipitation process. It has been shown that, besides the important role played by the width of the focused stream, the combined effect of reactor dimension, fluid properties, and flow condition significantly influenced the mixing condition and therefore the nucleation and growth process. When low water soluble molecules were co-precipitated together with polymeric stabilizer, competitive reactions resulted in the formation of two types of NPs, i.e., either with or without loading drug. The obtained results were interpreted by taking into consideration a new parameter representing the mismatching between the aggregations of the two precipitant species (polymer and drug), which played a decisive role in determining the size and polydispersity of the obtained NPs. Finally, the established microfluidic production procedure was examined from a drug delivery point of view, by encapsulating a clinically relevant drug in PMs. PMs containing mithramycin were prepared and tested in vitro as a therapeutic protocol for beta-thalassemia. In conclusion, the results of this study had demonstrated that microfluidics could facilitate the production of nanostructures for drug delivery purposes, and offer a novel method to control their properties including particle size, size distribution and pharmaceutical efficacy.