Overview and appraisal of the current concept and technologies for improvement of sublingual drug delivery.

Sublingual drug delivery is capable of achieving high bioavailability by avoiding first-pass liver extraction and enzymatic degradation in the gastrointestinal tract, as well as achieving rapid onset of effect. Thus, this route of administration can offer attractive therapeutic advantages for certain drugs as a convenient substitute for parenteral administration and has been applied successfully to a number of therapeutic conditions, especially urgent cardiovascular conditions and acute severe pain control. However, due to inherent limitations such as small sublingual mucosa area for absorption, primarily passive mechanism of transport, short residence time, and potential local irritation, a relatively small number of sublingual products have been successfully developed to date. In this Review, key concepts and technologies for potential improvement of sublingual drug delivery are reviewed. The optimal application of these concepts and technologies, together with clinical need for non-parenteral delivery, will hopefully broaden the development of sublingual drug delivery in the future.

Traditional Chinese medicinal formula Si-Wu-Tang prevents oxidative damage by activating Nrf2-mediated detoxifying/antioxidant genes.

BACKGROUND: Induction of Nrf2-mediated detoxifying/antioxidant genes has been recognized as an effective strategy for cancer chemoprevention. Si-Wu-Tang (SWT), comprising the combination of four herbs, Paeoniae, Angelicae, Chuanxiong and Rehmanniae, is one of the most popular traditional oriental medicines for women's diseases. The purpose of this study is to determine the effects of SWT on Nrf2 pathway in vitro and in vivo and to identify the active component(s). RESULTS: Cell viability and apoptosis were analyzed in the non-cancerous breast epithelial cell line MCF-10A after H2O2 treatment in the presence or absence of SWT using the Sulphorhodamine B assay, Annexin-V/Propidium iodide staining and flow cytometry. SWT strongly reduced H2O2 -induced cytotoxicity and apoptosis in MCF-10A cells. Expression of Nrf2 and Nrf2-regulated genes HMOX1 (heme oxygenase 1) and SLC7A11 (xCT) was evaluated by quantitative RT-PCR, Western Blot and immunocytochemistry. SWT strongly induced Nrf2-regulated genes at mRNA and protein levels and increased the nuclear translocation of Nrf2 in MCF-10A cells. The in vivo pharmacodynamic effect of SWT was evaluated in healthy female Sprague-Dawley rats. Short-term oral administration of SWT (1,000 mg/kg per day for six consecutive days) to rats resulted in an increased expression of Nrf2-regulated genes Hmox1 and Slc7A11 in the liver detected by quantitative RT-PCR. Among nine compounds that have been identified previously in the SWT products, z-liguistilide was discovered as the main component responsible for the effect of Nrf2 activation using the antioxidant response element-luciferase reporter gene assay. Z-liguistilide was confirmed with a high potency to induce Nrf2-regulated genes and Nrf2 nuclear translocation. CONCLUSIONS: Our results demonstrated that SWT and its component z-liguistilide are able to activate the Nrf2 pathway in non-cancerous cells and organs in vitro and in vivo, suggesting that SWT might be an orally effective and nontoxic agent for cancer chemoprevention.