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

Abstract

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.

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Identifiers

ORCID for X. Zhang: orcid.org/0000-0002-4375-1571

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