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, <i>in vitro</i> 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 AUC_0-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.