Cytoprotection of pancreatic β-cells and hypoglycemic effect of 2-hydroxypropyl-β-cyclodextrin: sertraline complex in alloxan-induced diabetic rats.

Sertraline, a selective inhibitor of serotonin reuptake, is widely used as antidepressant in diabetic patients for improvement of depression and glycemic control. Sertraline is poorly soluble in water, which limits its oral applicability. In this work we tried to improve the pharmaceutical properties of sertraline by complexation with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and evaluated the efficacy of the HPβCD:sertraline complex in prevention of alloxan-induced lesions in rats. The solubility of sertraline increased in the presence of HPβCD and the association constant for sertraline and HPβCD was equal to 4000 ± 1000 M(-1). Two-week treatment of diabetic animals with the HPβCD:sertraline complex improved pancreatic islet morphology and β-cell survival, which, in turn, reduced the severity of diabetes, as evidenced by lowering of blood glucose and glycated hemoglobin contents as well as normalization of serum insulin level and insulin sensitivity (HOMA-IR). The effect of the HPβCD:sertraline complex was strongly expressed in comparison with the antidiabetic effect of both the monopreparations, HPβCD and sertraline. It is suggested that the cyclodextrin derivative increased the pharmacological effect of sertraline, probably due to enhanced drug bioavailability.