International journal of pharmaceutics
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In this study, the effect of fluid physicochemical properties and the vibrating-mesh mechanism on the aerosols generated from vibrating-mesh nebulizers have been evaluated using fluids having a range of viscosity, surface tension and ion concentration. Two nebulizers were investigated: the Omron MicroAir NE-U22 (passively vibrating) and the Aeroneb Pro (actively vibrating) mesh nebulizers. For both devices, the total aerosol output was generally unaffected by fluid properties. ⋯ No clear effect of surface tension was observed on the performance of nebulizers employing a vibrating-mesh technology. However, when viscosity was low, reduced surface tension seemed advantageous in shortening the nebulization time and increasing the output rate, but for the Omron nebulizer this also increased the droplet VMD and decreased the FPF. This study has shown that vibrating-mesh nebulization was highly dependent on fluid characteristics and nebulizer mechanism of operation.
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Alkylcarbonates of gamma-cyclodextrins were produced and their inclusion complexes with four poorly water-soluble drugs of different structures and solubilities were prepared. The alkylcarbonates and the alkylcarbonate drug complexes were characterized by DSC and XRPD; the physical mixtures were used as control. Solubility capacities were evaluated by phase solubility studies. ⋯ The series of alkylcarbonates formed inclusion complexes with the drugs considered. Both XRPD and DSC analyses did not show neither the reflections of the crystalline structures nor the melting peaks of the drugs, respectively. These gamma-cyclodextrin derivatives can improve drug solubility and influence the drug release rates while the alkyl chain length may affect these properties.
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The purpose of this study was to develop a novel microsphere formulation of glucose oxidase (GOX) with high drug loading, encapsulation efficiency and bioactivity. GOX was encapsulated in alginate/chitosan microspheres (ACMS) using an emulsification-internal gelation, followed by GOX adsorption and polyelectrolyte coating method. The factors influencing GOX loading, encapsulation efficiency and activity of the loaded GOX were investigated. ⋯ The activity of GOX in ACMS was maintained and showed sustained production of H(2)O(2) as compared to free GOX. Around 90% of the original activity of immobilized GOX remained after lyophilization and storage at -20 degrees C for a month. These results suggest that the ACMS and the fabrication method are suitable for microencapsulation of proteins like GOX.
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As many anticancer agents paclitaxel is a substrate for ATP-binding cassette (ABC) transporters such as P-glycoprotein-mediated efflux, and its metabolism in humans mainly catalyzed by CYP 3A4 and 2C8. Genistein, an isoflavonoid, is supposed to be an inhibitor of some ABC transporters, and its oxidative metobolism catalyzed by CYP 3A4 and 2C8. The purpose of this study was to investigate the effect of orally administered genistein on the pharmacokinetics of paclitaxel administered through oral and intravenous (i.v.) route in rats. ⋯ Ten milligrams per kilogram genistein also significantly (p<0.05) increased the AUC (40.5% greater) and reduced the total clearance (CLt, 30% lower) of i.v. administered paclitaxel. The presence of genistein improved the systemic exposure of paclitaxel in this study. The pharmacokinetic interaction between them should be taken into consideration when paclitaxel is used with genistein or the dietary supplements full of genistein.
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Tumor vessel has been recognized as an important target for anticancer therapy. Cationic liposomes have been shown to selectively target tumor endothelial cells, thus can potentially be used as a carrier for chemotherapy agents. In this study, cationic liposomes containing 20 mol% cationic lipid dimethyl dioctadecyl ammonium bromide (DDAB) and loaded with doxorubicin (DOX) were prepared and characterized. ⋯ Although cationic liposomal DOX had higher tumor accumulation at 30 min after intravenous administration compared to control liposomes (p<0.05), DOX uptake of these liposomes at 24h post-injection was similar to that of PEGylated liposomal DOX (p>0.05) and approximately twice the levels of the free drug and non-PEGylated liposomes. In a murine tumor model generated using L1210 cells, increased survival rate was obtained with cationic liposomal DOX treatment compared to free DOX (p<0.01), neutral liposome control (p<0.01), as well as PEGylated liposomes (p<0.05). In conclusion, the cationic liposomal DOX formulation produced superior in vitro cytotoxicity and in vivo antitumor activity, and warrants further investigation.