ABSTRACT
Avocado (Persea americana Mill.; Lauraceae) seed-derived polyhydroxylated fatty alcohols (PFAs) or polyols (i.e., avocadene and avocadyne) are metabolic modulators that selectively induce apoptosis of leukemia stem cells and reverse pathologies associated with diet-induced obesity. Delivery systems containing avocado polyols have not been described. Herein, natural surface active properties of these polyols are characterized and incorporated into self-emulsifying drug delivery systems (SEDDS) that rely on molecular self-assembly to form fine, transparent, oil-in-water (O/W) microemulsions as small as 20 nanometers in diameter. Mechanistically, a 1:1 molar ratio of avocadene and avocadyne (i.e., avocatin B or AVO was shown to be a eutectic mixture which can be employed as a novel, bioactive, co-surfactant that significantly reduces droplet size of medium-chain triglyceride O/W emulsions stabilized with polysorbate 80. In vitro cytotoxicity of avocado polyol-SEDDS in acute myeloid leukemia cell lines indicated significant increases in potency and bioactivity compared to conventional cell culture delivery systems. A pilot pharmacokinetic evaluation of AVO SEDDS in C57BL/6J mice revealed appreciable accumulation in whole blood and biodistribution in key target tissues. Lastly, incorporation of AVO in SEDDS significantly improved encapsulation of the poorly water-soluble drugs naproxen and curcumin.
Subject(s)
Emulsions/chemistry , Persea/chemistry , Polymers/chemistry , Surface-Active Agents/chemistry , Animals , Cell Line, Tumor , Chemistry, Pharmaceutical/methods , Drug Delivery Systems/methods , Emulsions/administration & dosage , Emulsions/pharmacokinetics , Female , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Mice , Mice, Inbred C57BL , Polysorbates/chemistry , Solubility/drug effects , Tissue Distribution/physiology , Water/chemistryABSTRACT
BACKGROUND: Saffron, the dried stigmas of Crocus sativus L., is a highly valued agricultural product that is used mainly as a food coloring and flavoring agent. Three main secondary metabolites of Crocus sativus including crocin, picrocrocin, and safranal are responsible for the color, the bitter taste and for the odor and aroma, respectively. As a component of traditional medicine, saffron has been utilized as a medicinal herb for treating various ailments including cramps, asthma, liver disease, menstruation disorders, pain, and in the pathogenesis of cancer. HYPOTHESIS/PURPOSE: To summarize the recent published data on the chemo-preventive properties of Crocus sativus in cancer treatment. STUDY DESIGN: We conducted a non-systematic review of the literature. METHODS: A search of English-language literature was performed using Scopus, EMBASE and PubMed. We applied no restriction in time. Articles were searched using the keywords "Lung", "breast", "skin", "prostate", "leukemia", "cancer", "neoplasm", "tumor", "malignancy", "saffron", "crocus sativus", "crocin", "crocetin", "picrocrocin", and "safranal". RESULTS: Saffron has been reported to exert anti-tumor and anti-cancer effects in various types of cancer including lung cancer, breast cancer, leukemia, skin cancer and prostate cancer. This appears to be via various mechanisms including: the induction of apoptosis, arresting cell cycle progression, suppressing expression of matrix metalloproteinase, modulatory effects on some phase II detoxifying enzymes and decreasing expression of inflammatory molecules are potential mechanisms of saffron-induced anticancer effects. CONCLUSION: Saffron possesses potent anti-tumor properties and represents an efficacious and safe treatment.
