Development Of Lipid-Based Nanoscale Delivery Platforms Incorporating Enicostemma Littorale Extract For Targeted Glycemic Modulation

Abstract

Diabetes mellitus continues to be a major global health burden due to its rising prevalence and the limitations of conventional therapies, which often suffer from poor bioavailability, instability, and systemic side effects. Phytomedicine has been increasingly explored as an alternative approach, with Enicostemma littorale (EL) recognized for its potent antihyperglycemic, antioxidant, and insulin-sensitizing activities. However, the therapeutic potential of EL is restricted by its poor solubility and rapid metabolism. In the present study, lipid-based nanoscale delivery systems incorporating EL extract were developed to enhance its solubility, stability, and bioavailability for improved glycemic modulation. Nanoparticles were prepared by high-pressure homogenization using glyceryl monostearate, Compritol, Precirol, and stearic acid as lipid matrices, stabilized with Poloxamer 188, Tween 80, and lecithin. Compatibility of the extract with excipients was confirmed by FTIR, DSC. The optimized formulation exhibited a mean particle size of 162.4 ± 4.8 nm, PDI of 0.214, and zeta potential of –28.6 mV, indicating good stability. SEM analysis revealed spherical morphology with uniform distribution. The entrapment efficiency was 84.7 ± 2.3% with a production yield of 88.5 ± 3.2%. In vitro release studies demonstrated a biphasic release with ~22% drug release in the first 2 h followed by sustained release up to 78.6% at 24 h. Release was pH-dependent, showing better stability and controlled release under intestinal (74%) and physiological (79%) conditions compared to gastric pH (38%). Kinetic modeling indicated that the Higuchi model (R² = 0.981) provided the best fit, confirming diffusion-controlled release, while the Korsmeyer–Peppas model (n = 0.64) suggested anomalous transport. Overall, the study confirmed that lipid-based nanoscale carriers significantly enhanced encapsulation, stability, and controlled release of EL extract, highlighting their potential as an effective oral therapeutic strategy for targeted glycemic modulation in diabetes management.