title: Drug nanocarriers for cancer chemotherapy based on microemulsions: The case of Vemurafenib analog PLX4720.
abstract: Oil-in-water (O/W) microemulsions based on Tween 80 as the emulsifier and triacetin as the dispersed oil phase were formulated to be used as delivery vehicles of Vemurafenib analog PLX4720. PLX4720 is a lipophilic antitumor drug against various cancer types correlated with the BRAFV600Emutation. The limits of the single-phase region corresponding to O/W microemulsions as described by ternary phase diagrams were examined. Droplet size measurements determined by dynamic light scattering (DLS) showed mean droplet diameters equal to 10±0.1nm both in the presence and in absence of the drug. Cryogenic-transmission electron microscopy (Cryo-TEM) images of the microemulsions showed the existence of small structures with uniform size distribution having also average diameters of approximately 10nm. Electron paramagnetic resonance (EPR) spectroscopy applying the spin probing technique confirmed PLX4720 location in the oil cores excluding its participation in the surfactants monolayer. Furthermore, cell viability assays on colon cancer cell lines Colo-205 and HT29 showed that microemulsions did not exhibit any cytotoxicity when added in ratios between 0.005% v/v and 0.2% v/v. When the cells were treated with encapsulated PLX4720 at two different concentrations (0.063 and 0.12μΜ) the same response as when dissolved in classic DMSO was observed.
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., 11635, Athens, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Theochari
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., 11635, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Goulielmaki
authors.affiliation: Faculty of Biotechnology & Food Engineering, Technion-Israel Institute of Technology, 32000, Haifa, Israel.
authors.forename: Dganit
authors.initials: D
authors.lastname: Danino
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., 11635, Athens, Greece. Electronic address: vpapa@eie.gr.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Papadimitriou
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., 11635, Athens, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Pintzas
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., 11635, Athens, Greece.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Xenakis
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004655:Emulsions; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D011136:Polysorbates / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology; D013501:Surface-Active Agents / Q000737:chemistry; D014215:Triacetin / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004655:Emulsions; D007211:Indoles; D053769:Nanocapsules; C528407:PLX 4720; D011136:Polysorbates; D013449:Sulfonamides; D013501:Surface-Active Agents; D014215:Triacetin
keywords: Cell viability; Chemotherapy; Drug delivery; EPR; Microemulsions; PLX4720