Mitotane Loaded Poly(2-oxazoline) Micelles: Physico-Chemical Characterization and Cytotoxicity Studies in 2D & 3D in Vitro Models.Wednesday (08.05.2019) 17:20 - 17:40 Part of:
Adrenocorticol carcinoma (ACC) is rare tumor with poor prognosis . Mitotane (MT) has been used for treatment of ACC for decades either alone or in combination with other chemotherapeutic agents. Even at doses of MT up-to 6 g/L a day more than half of the patients do not achieve targeted plasma concentration (14-20mg/L) . These problems can be attributed to the MT low aqueous solubility (9.42e-06g/L) and unfavourable pharmacokinetic profile. Motivated by the extraordinary high drug loading of poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline)-block-poly(2-methyl-2-oxazoline) (A-pBuOx-A) based micelles for paclitaxel  we here aimed at development of MT loaded micelles which may enable an injectable formulation with increased water solubility which could help to circumvent toxicity and the long lag time. We successfully solubilize around 6g/L of MT in an aqueous formulation. MT loaded micelles formulations were characterized by FT-IR, DSC and XRD confirmed the amorphous nature of drug in the formulations. The polymer alone exhibited no toxicit yadrenal and liver cell culture models. By using the ACC model cell line NCI-H295 both in monolayers and tumor cell spheroids demonstrated micellar MT to exhibit comparable cytotoxicity as wehn dissolved in ethanol. In conclusion, we consider our micellar formulation a promising tool to alleviate major drawbacks of current MT treatment while retaining cytotoxic activity towards ACC in vitro.