The objective of the present work was to characterize the ability of liposomes and\ncyclodextrin (CyD) complexes to modulate the in vivo profile of fluticasone (FTZ). In vitro cell\ncompatibility tests were performed, exposing A549 cells to FTZ in the free form and FTZ associated\nto liposomes and complexed with CyD. The in vivo fate of a selected FTZ liposomal formulation\nand of several FTZ CyD complexes was achieved following intranasal instillation or pulmonary\nadministration in BALB/c mice, respectively. For pulmonary administration, an inhalation chamber\nwas constructed to enable the simultaneously pulmonary administration to six mice. Thirty minutes\nand 3 h after administration, mice were sacrificed, their blood, lungs, livers, and spleens were\nremoved, and FTZ level was determined by HPLC using an extraction procedure. The in vitro\ntests revealed no toxic effects of FTZ formulations, as cellular viability was always superior to 90%\nfor FTZ concentrations ranging from 5 to 60 microM 72 h after incubation. The in vivo biodistribution\nresults showed that FTZ incorporated in liposomes resulted in 20 and 30 times higher accumulation\nin the lungs in comparison with free FTZ, at 0.5 and 3 h after i.n. administration, respectively.\nFTZ associated to Hydroxypropyl-Gamma-cyclodextrin (HP-CyD) was the complex that permitted the\nhigher accumulation of FTZ in the lungs in comparison with the respective free form. The results\nalso suggest that the inhalation chamber apparatus can effectively facilitate the evaluation of in vivo\ninhalation. The establishment of an animal model of asthma allows us to further study the therapeutic\nefficacy of the developed FTZ formulations.
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