Ph.D. candidate Jaleesa Bresseleers, of the TU/e department of Biomedical Engineering, investigated a robust and scalable manufacturing process for nanocarriers and their building blocks. With these insights, the road to widely available clinical applications for nanocarriers has become much shorter.
It's
common to read about amazing new drugs and therapies in the newspapers, only to
have them disappear from the scene, never to be heard of again. The same
usually happens for novel therapeutic nanoparticle formulations, usually
nanocarriers that can be imagined as tiny balloons with a drug inside. One
reason for this is that during scale-up toward industry applications, it is
found that these formulations can't be reproducibly and cost-effectively
produced on a large scale, or even at all. Since nanocarriers are built from
multiple tiny building blocks, Jaleesa Bresseleers studied how these building
blocks and their formulation and processing parameters correlate to the
resulting nanocarrier characteristics.
Understanding
the process gives control over the results
Bresseleers
and coworkers found that by slightly adjusting the building blocks, they could
directly influence the size of the resulting nanocarriers. Simple processing
parameters such as concentration, solvent usage and mixing rates also had an
influence on the resulting size of the nanoparticles. These results provided
her with the ability to precisely tailor nanoparticles towards specific sizes.
Then, she
investigated the processing parameters in more detail using microfluidics. This
technique provided even more precise regulation of mixing rates by controlling
minute fluidic volumes. Bresseleers used it to obtain even better control over
the resulting nanoparticle sizes, and was able to produce nanoparticles with
different morphologies.
Ready for
production at scale
With this
knowledge, Bresseleers developed an efficient, scalable and highly controlled
manufacturing process. To ensure product quality and consistency, the quality
requirements of the European Medicines Agency (EMA) and U.S. food and drug
administration (FDA) were constantly taken into account. In the end, she
developed a continuous flow process for the large-scale production of
drug-loaded nanoparticles that can be readily translated to clinical-scale
production.
This
research is an important step to take nanoparticle formulations towards a
clinical product. It underscores how, as a general approach, it is important to
critically assess the formulation and processing parameters at an early stage
of nanoparticle design. Eventually, this will result in the creation of
nanoparticles with impact that extends beyond the conceptual phase.