PhSeZnCl A NOVEL SELENIUM COMPOUND WITH GPx-MIMETIC ACTIVITY: FORMULATION AND IN VITRO CHARACTERIZATION

Purpose. The aim of the present work is to formulate and characterize in vitro potentially respirable spray-dried microparticles (MP) of PhSeZnCl, a novel compound with GPx-mimetic activity, in order to improve the efficacy of the molecule and reducing the dose-dependent cytotoxicity. Methods. PhSeZnCl was encapsulated in poly(D-L-Lactide) (PLA) polymer by spray-drying with a Buchi B290 spray-dryer; likewise, PhSeZnCl powder was also spray-dried without the excipient. The MP were characterized in terms of size distribution with an accusizer C770, encapsulation efficiency by UV-vis spectrophotometry and morphology by SEM. The MP were tested on iMEFS (WT-KO) cells incubated in standard conditions (37°C, 5% CO2, DMEM) for 5 and 24 hours and were analyzed for cytotoxicity by MTT assay and morphology by fluorescence microscopy. For this purpose the MP were labeled with FITC. Results. The PLA MP loaded with PhSeZnCl showed spherical shape, narrow size distribution (5.34 μm), and a good content (16.9 ± 0.4%). The PhSeZnCl spray-dried powder had a comparable size distribution (5.48m) but a more irregular morphology. The in vitro analysis showed that the formulation of PhSeZnCl in MP decreased the toxicity in iMEFS-KO cells, at 4 hours after incubation, respect to the PhSeZnCl spray-dried powder and solutions, while no differences were observed in iMEFS-WT cells. The first studies of fluorescence microscopy showed that the formulation of PLA MP are partially internalized by cells. Conclusions. The formulation of PhSeZnCl in PLA MP seems to be potentially useful to reduce dose and time-dependent toxicity of the compound. Such formulations may have proper characteristics to be administered as a dry powder in the lungs.