Black Seed Oil Boosts Antidiabetic Activity of Glibenclamide: Development of Solidified Self Nanoemulsifying Drug Delivery System and Evaluation in Streptozotocin-Induced Diabetic Rat Model.

Abstract

Self nano-emulsifying drug delivery system (SNEDDS) has been widely used to enhance dissolution and bioavailability of glibenclamide (GB). In addition, black seed oil, containing bioactive thymoquinone (TQ), showed promising antihyperglycemic effect. Therefore, this work aims to design solid SNEDDS formulation composed of Black seed oil loaded with GB to enhance its antihyperglycemic activity. Different SNEDDS formulations were prepared and characterized for miscibility, dispersibility, droplet size, zeta potential, and in-vitro dissolution. Moreover, antidiabetic activity of prepared formulation against pure drug was evaluated using streptozotocin-induced diabetic rat model. The selected liquid SNEDDS (F7) formulation consisted of Kolliphor EL: Caproyl 90: BSO that produced nanoemulsion particles (24.9 ± 0.2nm). Different solidified formulations were prepared from F7, and the solidified (S4) formulation was selected as optimum formulation that showed GB and TQ had a DE% value of 73.16 ± 0.59 and 70.9%, respectively. Overall, both pure GB and GB-SNEDDS formulations significantly reduced blood glucose levels compared to the control diabetic group. The GB-SNEDDS showing superior efficacy (67% reduction, p = 5.5 × 10^-5) compared to pure GB (52% reduction, p = 1.5 × 10^-4). Moreover, the GB-SNEDD formulation has a significant (p = 0.0363) reducing action on blood glucose levels compared with the pure GB group. Present results showed that the prepared formulation boosted the antidiabetic activity of oral hypoglycemic drugs. This could open new avenues for using black seed oil as a natural bioactive hypoglycemic agent while preparing the SNEDDS formulation.