Oral Delivery of a High Quercetin Payload Nanosized Emulsion: In Vitro and In Vivo Activity Against B16-F10 Melanoma.

Quercetin is a natural compound that has several biological activities including anticancer activity. However, the use of this drug has been limited mostly because of its poor water solubility and low bioavailability. Therefore, the development of quercetin-loaded nanocarrier systems may be considered a promising advance to exploit its therapeutic properties in clinical setting including cancer treatment. This study evaluates the effect of orally administered nanosized emulsion containing quercetin (QU-NE) on the cytotoxicity activity against B16-F10 cells in vitro, and on subcutaneous melanoma in mice inoculated with B16-F1O cells. In vivo experiments, also evaluate the co-administration of quercetin with cisplatin in order to predict synergic effects and the renal and hepatic toxicity. The nanocarriers were prepared through the hot solvent diffusion associated with the phase inversion temperature methods. In vitro study showed reduction of cell viability in a concentration-depend manner for free quercetin and QU-NE. In vivo study, quercetin either as a free drug or colloidal dispersion was administrated at a dose of 5 mg kg(-1) twice a week for 17 days via oral route. Cisplatin was administrated at dose of 1 mg kg(-1) once a week intraperitoneally. Free quercetin and QU-NE reduced tumor growth, however, the reduction observed for QU-NE (P < 0.001 vs. control) was significantly higher than free quercetin (P < 0.05 vs. control). The association of both drugs did not show synergic effect. Besides, no renal or hepatic toxicities were observed after administration of free quercetin and QU-NE. These results suggest that an improvement in the oral bioavailability of quercetin occurred when this compound was dissolved in the oily phase of a nanosized emulsion, indicating that it might have a potential application in the treatment of melanoma.

Development of low density azithromycin-loaded polycaprolactone microparticles for pulmonary delivery.

CONTEXT: The development of low-density polymeric microparticles may be a useful approach to deliver antibiotics such as azithromycin into the lung. OBJECTIVE: The aim of this study was to develop azithromycin-loaded low density polycaprolactone microparticles by the double emulsion/solvent evaporation method. MATERIALS AND METHODS: Microparticles were prepared and characterized according to their physicochemical properties, drug loading, and drug release profiles. A full 23 factorial design was used to evaluate the effect of some independent variables on the drug loading and aerodynamic diameter of the particles. An in silico pulmonary deposition model was used to predict the lung deposition profiles for the formulations. RESULTS AND DISCUSSION: The resulting particles presented drug loading up to 23.1% (wt%) and mean geometric diameters varying from 4.0 µm to 15.4 µm. Bulk and tapped densities were low, resulting in good or excellent flow properties. SEM images showed spherical particles with a smooth surface. However, hollow inner structures were observed, which may explain the low values of bulk density. The estimated aerodynamic diameters ranged from 2.3 µm to 8.9 µm. The in silico pulmonary deposition profiles indicated, for some formulations, that a significant fraction of the particles would be deposited in the deeper lung regions. CONCLUSIONS: Statistical analysis demonstrated that not only drug loading but also the aerodynamic diameter of the microparticles is greatly affected by the preparation conditions. Overall, the results indicated that the low-density azithromycin-loaded microparticles with a relatively high respirable fraction may be obtained for the local treatment of lung infections.

Development of low density azithromycin-loaded polycaprolactone microparticles for pulmonary delivery.

CONTEXT: The development of low-density polymeric microparticles may be a useful approach to deliver antibiotics such as azithromycin into the lung. OBJECTIVE: The aim of this study was to develop azithromycin-loaded low density polycaprolactone microparticles by the double emulsion/solvent evaporation method. MATERIALS AND METHODS: Microparticles were prepared and characterized according to their physicochemical properties, drug loading, and drug release profiles. A full 2(3) factorial design was used to evaluate the effect of some independent variables on the drug loading and aerodynamic diameter of the particles. An in silico pulmonary deposition model was used to predict the lung deposition profiles for the formulations. RESULTS AND DISCUSSION: The resulting particles presented drug loading up to 23.1% (wt%) and mean geometric diameters varying from 4.0 µm to 15.4 µm. Bulk and tapped densities were low, resulting in good or excellent flow properties. SEM images showed spherical particles with a smooth surface. However, hollow inner structures were observed, which may explain the low values of bulk density. The estimated aerodynamic diameters ranged from 2.3 µm to 8.9 µm. The in silico pulmonary deposition profiles indicated, for some formulations, that a significant fraction of the particles would be deposited in the deeper lung regions. CONCLUSIONS: Statistical analysis demonstrated that not only drug loading but also the aerodynamic diameter of the microparticles is greatly affected by the preparation conditions. Overall, the results indicated that the low-density azithromycin-loaded microparticles with a relatively high respirable fraction may be obtained for the local treatment of lung infections.