Reversal of multiple drug resistance in cholangiocarcinoma by the glutathione S-transferase-pi-specific inhibitor O1-hexadecyl-gamma-glutamyl-S-benzylcysteinyl-D-phenylglycine ethylester.

Cholangiocarcinoma is markedly resistant to chemotherapy and has a dismal prognosis, but its mechanism of drug resistance is unknown. This study examines whether glutathione S-transferase-pi (GSTP1-1) is involved in resistance to anticancer drugs in cholangiocarcinoma and whether GSTP1-1-specific inhibitors can overcome this resistance. First, immunohistochemical examination disclosed strong staining of all our 17 cholangiocarcinoma specimens for GSTP1-1, irrespective of histological type.

Fractional contribution of lung, nasal and gastrointestinal absorption to the systemic level following nose-only aerosol exposure in rats: a case study of 3.7- micro m fluorescein aerosols.

Because absorption takes place from multiple sites of aerosol deposition, it is generally difficult to interpret systemic levels following nose-only inhalation in laboratory rodents. Therefore, this study attempted to determine the fractional contribution of lung, nasal and gastrointestinal (GI) absorption to the observed systemic level following nose-only aerosol exposure in rats using fluorescein as a model powder solute. Rats were treated orally with vehicle or activated charcoal, the latter diminishing GI absorption of fluorescein, and were subsequently nose-only exposed to 3.

Mucoadhesive beclomethasone microspheres for powder inhalation: their pharmacokinetics and pharmacodynamics evaluation.

The feasibility of prolonging drug action and/or reducing drug dosage using mucoadhesive beclomethasone dipropionate (BDP) microspheres for powder inhalation was investigated. BDP was spray-dried from ethanol solution or aqueous suspension systems dissolving a mucoadhesive polymer, hydroxypropylcellulose (HPC); this resulted in amorphous and crystalline BDP incorporation in the HPC microspheres (aBDP/HPC and cBDP/HPC; BDP-HPC ratio=1:4), respectively. These microspheres were administered as powder aerosols to healthy or antigen-induced, asthmatic guinea pigs, and BDP's retention in the lung (pharmacokinetics) and inhibitory duration with respect to eosinophil infiltration into the airways (pharmacodynamics) were compared to those for pure crystalline BDP (cBDP; 'control').