Self-Nanoemulsifying Formulation Improves Oral Bioavailability and Insulin Sensitizing Potency of Formononetin–Vitamin E Conjugate in Type 2 Diabetic Mice

The escalating incidence of obesity, diabetes, and insulin resistance has become a significant global health concern. In this study, we have developed a self-nanoemulsifying delivery system (SNEDS) of formononetin-vitamin E conjugate (VESylated-FMN) for improving its oral bioavailability and improving insulin sensitivity and glycemic control. The developed SNEDS were characterized using dynamic light scattering and transmission electron microscopy. Thereafter, the loading capacity, in vitro release, thermodynamic, and gastrointestinal stability of the developed formulation were evaluated. The safety and oral bioavailability of VESylated-FMN-SNEDS were assessed in Sprague–Dawley rats, whereas insulin-sensitizing potency was assessed in high-fat diet-induced type 2 diabetic mice. The VESylated-FMN-SNEDS quickly emulsified on dilution (droplet size ∼79.17 nm) and showed remarkable thermodynamic and gastrointestinal stability. The developed formulation demonstrated enhanced oral bioavailability (∼1.3-fold higher AUC0-t) of VESylated-FMN without liver and kidney injury. Consequently, VESylated-FMN-SNEDS significantly improves insulin sensitivity and glycemic control in HFD-fed mice compared to VESylated-FMN by upregulating the transcript level of insulin-sensitizing genes. Therefore, the SNEDS formulation could be an effective strategy to augment the oral bioavailability and insulin-sensitizing potency of VESylated-FMN.