Development of Mitotane Lipid Nanocarriers and Enantiomers: Two-in-One Solution to Efficiently Treat Adreno-Cortical Carcinoma
Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with a poor prognosis. Treatment options for advanced
ACC are limited. Indeed, radical tumor resection can lead to local or metastatic recurrence, and mitotane (Lysodren®), the only recognized
adrenolytic drug, offers modest response rates, notably due to some of its physico-chemical and pharmacological properties (i.e.
hydrophobicity, low bioavailability). Meantime, high cumulative doses of Lysodren® usually cause systemic toxicities. To reduce adverse
health effects, the search of safe and efficient mitotane nano-formulations as well as the full characterization and testing of its enantiomers
can represent valuable therapeutic options. Interestingly, recent investigations showed that solid lipid nanoparticles (SLN) and
nanostructured lipid carriers (NLC) could considerably improve the efficacy of mitotane (i.e. enhanced solubility and bioavailability,
progressive release of the loaded drug into blood and targeted tissues) as well as its safety (i.e. lower toxicity, higher biocompatibility).
These two nano-carriers for mitotane delivery and targeting are of particular interest over other polymeric particles (i.e. low-cost, efficient
and simple scaling to an industrial production level following green methods). Besides, emerging studies suggested that the S-(-)-
mitotane is more potent than the R-(+)-mitotane for ACC treatment. Therefore, the production of pure and active S-(-)-mitotane might offer
synergic or additive benefits for ACC patients when combined to solid lipid-based nanocarriers. In this review, we first provide an
updated overview of the ACC disease before emphasizing on the promising mitotane drug nano-systems, as well as on the separation,
purification and production of single mitotane enantiomer using state-of-art chromatographic-based methods.
Keywords: Adreno-cortical carcinoma, cancer endocrinology, chiral separation, endocrine cancer chemotherapy, lysodren®, medicinal chemistry,
mitotane enantiomers, mitotane pharmacology, mitotane synthesis, nanostructured lipid carriers, nanomedicine, simulated moving bed
chromatography, solid lipid nanoparticles, supercritical fluid chromatography, translational medicine
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