Combination of Microfluidics with SAXS for the investigation of pharmaceutical formulations

Aghiad Ghazal

Abstract

Due to the latest advancements in microfluidics and synchrotron facilities, researchers started
exploring the possibility of harnessing the benefits of combining both fields of science to
address questions that were deemed unanswerable. Moreover, this combination made
experiments that were believed to be impossible to perform, more practically viable,
financially affordable and doable in a reasonable time.
Some of the questions that have eluded scientists include understanding the very early
structural kinetics behind the folding of proteins, which experimentally became possible
using microfluidic systems. X-ray compatible microfluidic systems proved reliable and
suitable for performing protein-folding experiments all the while permitting the probing of Xray
radiation to detect reactions in the microsecond scale.
Other questions include understanding the early interaction of Ca2+ ions with drug
nanocarriers and the effect it has on its internal structure. Such experiments provide valuable
information for future investigations of the drug release activity of the nanocarriers.
The combination of microfluidics and synchrotron X-ray is also exploited to address
biological questions, however, other non-biological experiments have also made use of this
successful merger to discover novel rheological phenomena that can only occur on a
microscale in microchannels under non-equilibrium conditions due to strain and shear forces.
Being able to perform a range of experiments with as little as few nanoliters of sample,
opened the door for investigating expensive samples with a large number of experimental
parameters compared to conventional methods where only few experimental parameters were
addressed with samples as large as few milliliters in volume required.
The successful merger of microfluidics and synchrotron X-ray inspired us to explore
interesting nanoparticles that have been gaining interest in the recent years for drug delivery applications and bio-imaging. These drug nanocarriers are superior in terms of their
efficiency in solubilizing various drugs and may help in controlling their release. They are
lipid based, non-lamellar with a cubic and hexagonal crystalline internal structure thus called
cubosomes and hexosomes, respectively.
Unfortunately, information about the early formation of these nanocarriers and their
interaction with drug and other molecules is scarce in literature due to the lack of efficient
tools to investigate them thoroughly. Therefore, we became enthusiastic about performing
mixing experiments on these nanoparticles using microfluidics while performing in situ
characterization using synchrotron small angle X-ray scattering (SAXS). We were able to
locate the time range at which these nanocarriers start interacting with molecules and observe
them as they evolve under non-equilibrium conditions to form the final product.

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