title: Development and in vitro evaluation of deacety mycoepoxydiene nanosuspension.
abstract: Deacety mycoepoxydiene (DM), extracted from Phomopsis sp. A123 of thalassiomycetes, is a novel and potent anti-cancer agent. Due to its physicochemical characteristics, the drug, a poorly water-soluble weak acid, shows poor solubility and dissolution characteristics. To improve the solubility and dissolution, formulation of DM as nanosuspension has been performed in this study. Nanosuspensions were developed by high-pressure homogenization (HPH) (DissoCubes(®) Technology) and transformed into dry powder by freeze-drying. The nanosuspension produced was then investigated using optical microscope, photon correlation spectroscopy (PCS), zeta potential measurement, SEM, TEM, AFM, DSC and XRD. To verify the theoretical hypothesis on the benefit of increased surface area, in vitro saturation solubility and dissolution profile were investigated. In addition, the in vitro cell cytotoxicity was examined. Results showed that a narrow size distributed nanosuspension composed of unchanged crystalline state with a mean particle size of 515±18 nm, a polydispersity index of 0.12±0.03 and a zeta potential of -23.1±3.5 mV was obtained. In the in vitro dissolution test an accelerated dissolution velocity and increased saturation solubility could be shown for the MD nanosuspension. The in vitro cytotoxicity experiments provided evidence for an enhanced efficacy of the DM nanosuspension formulation compared to free DM solution. Taken together, these results illustrate the opportunity to formulate DM in nanosuspension form as an anti-prostate cancer delivery system.
authors.affiliation: College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, PR China.
authors.forename: Yancai
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Liu
authors.forename: Dianrui
authors.initials: D
authors.lastname: Zhang
authors.forename: Xihui
authors.initials: X
authors.lastname: Gao
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Cunxian
authors.initials: C
authors.lastname: Duan
authors.forename: Lejiao
authors.initials: L
authors.lastname: Jia
authors.forename: Feifei
authors.initials: F
authors.lastname: Feng
authors.forename: Yaojian
authors.initials: Y
authors.lastname: Huang
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008968:Molecular Conformation; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004852:Epoxy Compounds; D011753:Pyrones; C557709:deacety mycoepoxydiene