College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, PR China.
Colloids Surf B Biointerfaces. 2011 Apr 1;83(2):189-97. doi: 10.1016/j.colsurfb.2010.10.029. Epub 2010 Oct 21.
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.
脱乙酰基 mycoepoxydiene（DM）是从海洋真菌 Phomopsis sp. A123 中提取的一种新型强效抗癌药物。由于其理化特性，该药物是一种水溶性差的弱酸，表现出较差的溶解度和溶解特性。为了提高其溶解度和溶解特性，本研究将 DM 制成纳米混悬剂。纳米混悬剂通过高压均质（HPH）（DissoCubes（®）技术）制备，并通过冷冻干燥转化为干粉。然后使用光学显微镜、光相关光谱（PCS）、zeta 电位测量、SEM、TEM、AFM、DSC 和 XRD 对纳米混悬剂进行了研究。为了验证表面积增加带来益处的理论假设，考察了体外饱和溶解度和溶解曲线。此外，还考察了体外细胞毒性。结果表明，得到了一种由不变晶态组成的、粒径分布窄的纳米混悬剂，平均粒径为 515±18nm，多分散指数为 0.12±0.03，zeta 电位为-23.1±3.5mV。在体外溶解试验中，DM 纳米混悬剂的溶解速度加快，饱和溶解度增加。体外细胞毒性实验为 DM 纳米混悬剂制剂比游离 DM 溶液具有更高疗效提供了证据。总之，这些结果表明可以将 DM 制成纳米混悬剂形式作为治疗前列腺癌的给药系统。
