Abstract

The therapeutic efficacy of vildagliptin (DPP-4 inhibitor) in conventional solid dosage forms is limited by rapid systemic clearance and low intestinal permeability, resulting in frequent dosing and suboptimal glycemic control. This study aimed to address these limitations by developing vildagliptin-loaded liposomes enhanced with fenugreek (Trigonella foenumgraecum) to improve antidiabetic activity and sustain drug release through inhibition of GLP-1 and GIP degradation. Liposomes were prepared via the ether injection method and optimized using a full factorial design, with lecithin, cholesterol, and chitosan/PLGA as independent variables and drug entrapment efficiency and cumulative release as dependent responses. Characterization was performed using FTIR, SEM, zeta potential analysis, and in vitro release studies in a pH 1.2 buffer over 8 hours following the USP paddle method. Entrapment efficiency ranged from 87.99% to 92.52%, with the PLGA-based formulation (PLFE-4) showing the highest performance. SEM confirmed uniform, spherical vesicles averaging 93.5 nm in diameter. Release kinetics followed a zero-order model, indicating sustained drug release. Level A IVIVC modeling using ex vivo release data predicted that PLFE-4 exhibits reduced Cmax and delayed Tmax. In vivo studies in alloxan induced diabetic rats demonstrated sustained glycemic control for up to 8 hours and maintenance of HbA1c levels between 6% and 8%. These findings suggest that fenugreek-integrated vildagliptin liposomes represent a promising sustained-release platform for effective management of type II diabetes mellitus.

Key words: Liposome, vildagliptin, fenugreek, chitosan, PLGA, antidiabetic activity