Urtica dioica SmartLipids: Formulation, Characterization, and In vivo Evaluation as a Promising Antidiabetic Nanocarrier

Abstract

Urtica dioica (UD) has demonstrated promising antidiabetic activity by modulating glucose metabolism and lipid homeostasis. However, its clinical translation is limited by poor aqueous solubility, rapid degradation, and low gastrointestinal absorption, which significantly reduce oral bioavailability. Lipid-based nanocarriers, particularly third-generation SmartLipids (SL) systems, have emerged as promising platforms for improving the stability, solubility, and intestinal uptake of poorly soluble phytoconstituents. UD-loaded SmartLipids were prepared using a heat homogenization technique employing a mixture of solid lipid (Cetyl alcohol, Beeswax, Cocoa Butter, Stearic acid, and Glyceryl Monostearate) and liquid lipid (Oleic acid), and stabilized with Tween-80 as a surfactant. Homogenization was performed, followed by ultrasonication to obtain nanosized particles. The formulations were optimized based on the particle size, zeta potential, polydispersity index (PDI), and entrapment efficiency. The structural compatibility and morphology were evaluated using FTIR and transmission electron microscopy. In vitro drug release studies and stability analysis were conducted, followed by in vivo antidiabetic evaluation in streptozotocin-induced diabetic rats. The optimized UD smart lipid formulation exhibited a mean particle size of ~56.47 nm, PDI < 0>89.28%). The release profile demonstrated a biphasic pattern with an initial burst followed by sustained release over 24 hours. In vivo studies showed significant reductions in fasting blood glucose, improved insulin sensitivity, and restoration of lipid profiles compared. The optimized UD-SL formulation exhibited a mean particle size of 56.47 ± 4.42 nm, PDI < 0.3, zeta potential of approximately −25.4 ± 6.32 mV, and entrapment efficiency of 89.28 ± 0.38%. The formulation exhibited a biphasic drug-release pattern, with an initial burst followed by sustained release for up to 18 hours. In vivo studies demonstrated a significant reduction in fasting blood glucose levels compared to the diabetic control (p < 0.05), along with improved insulin sensitivity and significant normalization of lipid profile parameters when compared with conventional UD extract. The potential of SL to serve as a technologically advanced system for oral delivery of UD was confirmed in this study, which demonstrated improved overall capability of UD owing to its nanoscale size and negatively charged surface. The developed UD-SL significantly improved the delivery and antidiabetic efficacy of UD, likely due to enhanced solubility, nanoscale particle size, and improved gastrointestinal absorption. These findings highlight the potential of SL-based nanocarriers as an effective oral delivery platform for plant-derived antidiabetic compounds, although further pharmacokinetic and long-term safety studies are required to confirm their clinical applicability.