JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.115, 2026 (SCI-Expanded, Scopus)
Diabetes mellitus (DM) continues to be a significant worldwide health problem, with restrictions on existing treatment options because of the poor bioavailability of many active compounds and their adverse effects. Harmine (HRM), a beta-carboline alkaloid with antidiabetic and antioxidant properties, has low aqueous solubility and limited oral absorption, which restricts its clinical potential. Our study aimed to develop harmine (HRM)-containing NE formulation (HRM-NE) to overcome these limitations and characterize it in vitro (TEM image, zeta potential, pH measurement, entrapment efficiency, droplet size, size distribution, and in vitro release) and in vivo (hypoglycemic effect, antioxidant effect, and liver tissue's histological evaluation). The HRM-NE formulation had a droplet size of around 200 nm with PDI<0.3 (a narrow size distribution), and a suitable zeta potential value (-38.67 mV) for acceptable physical stability. Its pH value was around 4. The % entrapment efficiency value for the HRM-NE formulation was 98.23 +/- 0.87%. The blood glucose levels of diabetic rats in the groups treated with pure HRM (5, 10, and 15 mg/kg) or HRM-NE (5, 10, and 15 mg/kg HRM equivalent) administered diminished significantly over time (p < 0.05). On the 21(st) day of the application, the blood glucose level of diabetic rats in the D-HRM-NE 15 group was significantly less than that of diabetic rats in the D-HRM 15 group (p < 0.05). Compared with the DC group (diabetic control), liver SOD activity and GSH levels of diabetic rats administered HRM or HRM-NE (for all doses) were significantly increased, and blood glucose, liver MDA and serum AST and ALT levels were reduced significantly (p < 0.05). In particular, the D-HRM-NE 15 group caused a noticeable decrease in oxidative stress markers and marked improvement in diabetic rats' liver tissues. The results indicate that NE formulation is a potential delivery system for the oral administration of HRM.