Effective formulation of highly water insoluble drugs remains a major challenge in pharmaceutical technology. Polymeric micelles have been discussed and utilized for many years for this purpose, but their translation to clinical practice has been slow. One of the main limitations is the poor drug loading and the limited absolute drug concentration that can be achieved using polymer micelles. Recently, amphiphilic triblock copolymers comprising poly(2-methyl-2-oxazoline) and a wide range of different hydrophobic poly(2-oxazoline)s have been described as extremely efficient solubilizers for a wide range of extremely water-insoluble drugs. Not only the relative drug concentration is very high, in several cases exceeding 50 wt.%, but also the absolute drug concentration can be very high, with apparent solubility increases of &gt;10.000 fold for several drugs. Here, we describe a novel nanoformulation of mitotane, an important therapeutic agent in the treatment of rare adrenocortical carcinoma. Structure property relationships are elucidated and the resulting ultra-high capacity nanoformulations are tested in 2D and 3D tumor models. Interestingly, while in 2D, the drug loaded micelles are slightly less active than the control, the situation is reversed in the 3D model. In summary, the novel mitotane nanoformulation exhibits promising characteristics which warrant further studies.

Novel ultra-high capacity nanoformulations of extremely hydrophobic drugs and their evaluation in 3D cancer models

2019 Fall National Meeting

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