Adrenocortical carcinoma (ACC) is a rare tumor and prognosis is overall poor but heterogeneous. Mitotane (MT) has been used for treatment of ACC for decades, either alone or in combination with cytotoxic chemotherapy. Even at doses up to 6 g per day, more than half of the patients do not achieve targeted plasma concentration (14–20 mg L⁻¹) even after many months of treatment due to low water solubility, bioavailability, and unfavorable pharmacokinetic profile. Here a novel MT nanoformulation with very high MT concentrations in physiological aqueous media is reported. The MT‐loaded nanoformulations are characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X‐ray diffraction which confirms the amorphous nature of the drug. The polymer itself does not show any cytotoxicity in adrenal and liver cell lines. By using the ACC model cell line NCI‐H295 both in monolayers and tumor cell spheroids, micellar MT is demonstrated to exhibit comparable efficacy to its ethanol solution. It is postulated that this formulation will be suitable for i.v. application and rapid attainment of therapeutic plasma concentrations. In conclusion, the micellar formulation is considered a promising tool to alleviate major drawbacks of current MT treatment while retaining bioactivity toward ACC in vitro.

中文翻译：

---

具有高载药量和溶解度的胶束线粒体制剂：在2D和3D体外肿瘤模型中的理化特性和细胞毒性研究。

肾上腺皮质癌（ACC）是一种罕见的肿瘤，预后总体较差但异质。线粒体（MT）单独或与细胞毒性化学疗法一起用于治疗ACC已数十年了。即使每天剂量高达6 g，也有超过一半的患者未达到目标血浆浓度（14–20 mg L ^-1），即使由于水溶性低，生物利用度低和药物动力学特性不良而经过数月的治疗。此处报道了在生理水介质中具有很高MT浓度的新型MT纳米制剂。载有MT的纳米制剂的特征在于傅立叶变换红外光谱，差示扫描量热法和X射线粉末衍射，证实了药物的无定形性质。该聚合物本身在肾上腺和肝细胞系中未显示任何细胞毒性。通过在单层和肿瘤细胞球体中使用ACC模型细胞系NCI-H295，胶束MT表现出与乙醇溶液相当的功效。假定该制剂将适合于静脉内施用和快速达到治疗性血浆浓度。结论，