Fluorotronics Inc., USA
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, 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).
We will show that pure and active S-(-)- mitotane is more potent than pure R-(+)-mitotane for ACC treatment, and might offer synergic or additive benefits in vivo when adequately combined to well-prepared and characterized solid lipid-based nanocarriers.
Keywords: Adreno-Cortical Carcinoma (ACC); solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC); Nanomedicine; Mitotane; Enantiomers; Cancer Therapy.