Preparation, characterization, in vitro drug release and anti-inflammatory of thymoquinone-loaded chitosan nanocomposite.

In this study, we formulated Thymoquinone-loaded nanocomposites (TQ-NCs) using high-pressure homogenizer without sodium tripolyphosphate. The TQ-NCs were characterized and their anti-inflammatory determined by the response of the LPS-stimulated macrophage RAW 264.7 cells in the production of nitric oxide, prostaglandin E2, tumor necrosis factor-α, interleukin-6, and interleukin-1ß. The physicochemical properties of TQ-NC were determined using different machines. TQ was fully incorporated in the highly thermal stable nanoparticles. The nanoparticles showed rapid release of TQ in the acidic medium of the gastric juice. In medium of pH 6.8, TQ-NC exhibited sustained release of TQ over a period of 100 h. The results suggest that TQ-NC nanoparticles have potential application as parenterally administered therapeutic compound. TQ-NC effectively reduce production of inflammatory cytokines by the LPS-stimulated RAW 264.7 cells, indicating that they have anti-inflammatory properties. In conclusion, TQ-NC nanoparticles have the characteristics of efficient carrier for TQ and an effective anti-inflammatory therapeutic compound.

Inclusion complex of clausenidin with hydroxypropyl-ß-cyclodextrin: Improved physicochemical properties and anti-colon cancer activity.

The long-term objective of the present study was to prepare, physicochemically characterize and determine the anticancer of clausenidin/hydroxypropyl-ß-cyclodextrin (Clu/HPßCD) inclusion complex. We used differential scanning calorimetry, X-ray diffractometer, fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometer and 13C and 1H nuclear magnetic resonance followed by in vitro anticancer assays. The orientation and intermolecular interactions of Clausenidin within cyclodextrin cavity were also ascertained by molecular docking simulation accomplished by AutoDock Vina. The guest molecule was welcomed by the hydrophobic cavity of the host molecule and sustained by hydrogen bond between host/guest molecules. The constant drug release with time, and increased solubility were found after successful complexation with HPßCD as confirmed by physicochemical characterizations. Clausenidin had greater cytotoxic effect on colon cancer HT29 cells when incorporated into HPßCD cavity than dissolved in DMSO. Also, from a comparison of cell viability between normal and cancer cells, a reduced side effect was observed. The Clu/HPßCD inclusion complex triggered reactive oxygen species-mediated cytotoxicity in HT29 cells. The inclusion complex-treated HT29 cells showed cell cycle arrest and death by apoptosis associated with caspases activation. The presence of HPßCD seems to aid the anticancer activity of clausenidin.

Anticancer effect of dentatin and dentatin-hydroxypropyl-ß-cyclodextrin complex on human colon cancer (HT-29) cell line.

INTRODUCTION: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that its complexation with hydroxy-ß-cyclodextrin (HPßCD) will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HPßCD complex were demonstrated in human colon HT-29 cancer cells. MATERIALS AND METHODS: After the human colon HT-29 cancer cells were treated with DEN and DEN-HPßCD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as the Bcl-2 family of proteins. RESULTS: At 3, 6, 12, and 24 µg/mL exposure, DEN and DEN-HPßCD complex significantly affected apoptosis in HT-29 cells through the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53, p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HPßCD complex also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8, and -9. CONCLUSION: Results of this study indicate that the apoptotic pathway caused by DEN and DEN-HPßCD complex are mediated by the regulation of caspases and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest that DEN-HPßCD complex may have chemotherapeutic benefits for colon cancer patients.