ABSTRACT
The purpose of this study is to investigate the enantioselectivity of norgestrel (NG) transdermal permeation and the potential influence of linalool and lipids on the enantioselectivity. In vitro skin permeation studies of NG across the excised rat skins were performed with Valia-Chien diffusion cells, and the permeation samples were analyzed by enantioselective HPLC. The possible enantioselective permeation of NG across intact rat back skin and lipids extracted rat back skin and the influence of linalool were evaluated. The skin permeation rate of dl-NG was two times higher than that of l-NG when donor solutions (EtOH/H2O 2 : 8, v/v) containing l-NG or dl-NG. It may be mainly attributed to the solubility discrepancy between enantiomer and racemate. The enantioselective permeation of dl-NG across intact rat skin was observed when the donor solutions containing dl-linalool. The permeation flux of l-NG was 22% higher than that of d-NG. But interestingly, the enantioselective permeation of dl-NG disappeared under the same experimental condition except that the lipid extracted rat skin was used. Attenuated total reflection-fourier transform infrared spectroscopy analysis of stratum corneum showed that the wave number for asymmetric CH2 stretching vibrations of lipids treated with dl-linalool was greater than that of the control. The results indicated that the enantioselective permeation of NG may be contributed by the interaction between dl-linalool and lipids. More than half of lipids were composed of ceramides. The stereospecific interaction maybe existed among chiral enhancer (linalool), lipids (ceramides) and/or chiral drugs (NG).
ABSTRACT
AIM: To observe the growthinhibiting cell cycle-modifying and apoptosis-inducing effects of satraplatin on human ovarian carcinoma cell line A2780, and to explore its possible mechanism. METHODS: The effect of satraplatin on A2780 cells proliferation was determined using MTT, and the change in cell cycle was analyzed using PI staining. Morphologic change was visualized by fluorescence and electron microscopy. AnnexinV-FITC/PI staining multiparameter flow cytometry and immuno- histochemical TUNEL assay were used to detect apoptotic cells. The activity of caspase-3 and the effect of pan-caspase inhibitor on cell viability were measured as well. RESULTS: The growthinhibiting and apoptosis-inducing effects of satraplatin were dose-dependent and similar to those of cisplatin. Satraplatin mainly caused A2780 cell accumulation in S phase accompanied by minor accumulation in G2/M phase. Cells treated with satraplatin exhibited typical morphology of apoptosis. Satraplatin-induced increase in caspase-3 activity of A2780 cells was concentration-dependent. The viability of A2780 cells was affected by pan-caspase inhibitor z-VAD-fmk in a dose-dependent manner under certain concentration of z-VAD-fmk. CONCLUSION: Satraplatin-induced apoptosis in A2780 in vitro was observed. Caspase-dependent and independent pathways were involved in apoptosis induced by satraplatin, and the latter included caspase-3 dependent and non-caspase-3 dependent pathways.