Abstract
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
Current Medicinal Chemistry
Title:Development of Mitotane Lipid Nanocarriers and Enantiomers: Two-in-One Solution to Efficiently Treat Adreno-Cortical Carcinoma
Volume: 19 Issue: 34
Author(s): F. Menaa and B. Menaa
Affiliation:
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
Abstract: 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.
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Cite this article as:
Menaa F. and Menaa B., Development of Mitotane Lipid Nanocarriers and Enantiomers: Two-in-One Solution to Efficiently Treat Adreno-Cortical Carcinoma, Current Medicinal Chemistry 2012; 19 (34) . https://dx.doi.org/10.2174/092986712804143376
DOI https://dx.doi.org/10.2174/092986712804143376 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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