Design, Optimization, And Pharmacodynamic Evaluation Of Linagliptin-Loaded Lipospheres For Improved Glycemic Control

Abstract

The present study aimed to design, optimize, and evaluate linagliptin-loaded lipospheres for enhanced bioavailability and sustained glycemic control in type 2 diabetes mellitus. Lipospheres were prepared using stearic acid and cetyl alcohol as lipid carriers and optimized through a Box–Behnken design. The optimized formulation (F15) exhibited a particle size of 220.12 nm, high entrapment efficiency (81.15%), and a zeta potential of –36.25 mV, indicating good stability. In vivo pharmacodynamic studies were performed in streptozotocin-induced diabetic rats. Treatment with linagliptin lipospheres resulted in significant (p<0.05) reductions in fasting blood glucose levels and improvements in body weight compared to the diabetic control group. Moreover, lipid profile parameters such as total cholesterol, triglycerides, and LDL were markedly decreased, while HDL levels were restored. Serum biomarkers including ALT, AST, MDA, SOD, GSH, and insulin were also favorably modulated, indicating hepatoprotective and antioxidant potential of the formulation. The findings suggest that the developed lipospheres provide sustained drug release, enhanced therapeutic efficacy, and overall improved glycemic and metabolic outcomes, making them a promising drug delivery system for the effective management of diabetes mellitus.