In this study, trans-dehydrocrotonin was encapsulated into microspheres prepared using the double emulsion method. The physicochemical characteristics of the DCTN-loaded microspheres were studied (encapsulation efficiency, particle size distribution, FT-IR, 1H-NMR). The in vitro release profile of DCTN-loaded microspheres was evaluated according to standard dissolution test and drug content was evaluated at 244 nm. The in vivo hypoglycemic activity of DCTN-loaded microspheres was evaluated in normal and hyperglycemic female Swiss mice (25-35 g body weight) through two different sets of experiments. In the first one, normal glycemic mice were separated in three groups of six animals each, which were randomly established as control and treated groups. In a second set of experiment, diabetes was induced by three consecutive intraperitoneal injections of streptozotocin (60 mg/kg in citrate buffer 0.01 M, pH 4.5) with intervals of 24 h. Diabetic mice were then randomly separated into three groups of 10 animals each. The treatment of both normal and hyperglycemic animals was performed by a daily oral administration of DCTN suspension in 5 % v/v tween 80 or DCTN-loaded microspheres (50 mg/kg). The results demonstrated that the encapsulation efficiency of DCTN into microspheres was about 85.46 ± 3.87 % and  the mean particle size of microspheres was 3.11 ± 0.56 mm. The in vitro kinetic profile of DCTN-loaded microspheres was initially fairly fast with a burst effect of 41.5% (k=4.839 ± 0.503) followed by a slower and controlled release attaining a maximum drug released (roughly 60%) within 3 days. The decrease of blood glucose levels was 14.3 % and 26.8 % after the treatments with DCTN suspension and DCTN-loaded microspheres, respectively. However, the hypoglycaemic effect of DCTN-loaded microspheres was statistically significant only at the 7th day of the treatment as compared with that one of the untreated animals. The encapsulation increased the effectiveness of DCTN in normal glycemic mice. Chemotherapeutic potential of these particles can improve the management of drug therapy in hyperglycaemic patients. Support by: CNPq/MCT, CAPES.

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