Fluvastatin-Loaded Emulsomes Exhibit Improved Cytotoxic and Apoptosis in Prostate Cancer Cells.

Fluvastatin (FLV) is known to inhibit the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), which is over-expressed in various cancers. FLV has been reported to decrease cancer development and metastasis. However, because of low bioavailability, extensive first-pass metabolism and short half-life of FLV (1.2 h), it is not appropriate for clinical application. Therefore, FLV-loaded emulsomes were formulated and optimized using Box-Behnken experimental design to achieve higher efficiency of formulation. Antitumor activity of optimized FLV-loaded emulsomes was evaluated in prostate cancer cells using cell cytotoxicity, apoptotic activity, cell cycle analysis, and enzyme-linked immunosorbent assay. The FLV-loaded emulsomes exhibited a monodispersed size distribution with a mean particle size less than 100 nm as measured by zetasizer. The entrapment efficiency was found to be 93.74% with controlled drug release profile. FLV-EMLs showed a significant inhibitory effect on the viability of PC3 cells when compared to the free FLV (P < 0.0025). Furthermore, FLV-EMLs showed significant arrest in G2/M and increase in percentage of apoptotic cells as compared to free FLV. FLV-EMLs were more effective than free FLV in reducing mitochondrial membrane potential and increase in caspase-3 activity. These results suggesting that FLV-EMLs caused cell cycle arrest which clarifies its significant antiproliferative effect compared to the free drug. Therefore, optimized FLV-EMLs may be an effective carrier for FLV in prostate cancer treatment.

Large-Ring Cyclodextrins as Chiral Selectors for Enantiomeric Pharmaceuticals.

Large-ring cyclodextrins (CD) are cyclic glucans composed of 9 or more α-1,4-linked glucose units. They are minor side products of bacterial glucanotransferases (CGTases, EC 2.4.1.19) and have previously been available only in very small amounts for studies of their properties in supramolecular complex formation reactions. We engineered a CGTase to synthesize mainly large-ring CD facilitating their preparation in larger amounts. By reversed phase chromatography, we obtained single CD samples composed of 10 to 12 glucose units (CD10, CD11, and CD12) with a purity of >90 %. Their identity was confirmed by high resolution mass spectrometry and fragmentation analysis. We demonstrated the non-toxicity of CD10-CD12 for human cell lines by a cell proliferation assay and impedimetric monitoring. We then showed that CD10 and CD11 are efficient chiral selectors for the capillary electrophoretic separation of the enantiomeric pharmaceuticals fluvastatin, mefloquine, carvedilol, and primaquine.