Design and Evaluation of Compritol–Oleic Acid Nanostructured Lipid Carriers: A New Approach to Type 2 Diabetes Therapy

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder caused by reduced insulin production and sensitivity. Despite advancements in antidiabetic medications, many patients struggle with poor glycemic control. Combining drugs like sitagliptin (STG) and glipizide (GPZ) can improve treatment efficacy, but their low solubility and rapid excretion limit their effectiveness. To address these challenges, this study developed novel compritol and oleic acid-based nanostructured lipid carriers (NLCs) for the co-delivery of STG and GPZ. The NLCs were prepared using a modified microemulsion technique and optimized using the Box-Behnken model, focusing on particle size, zeta potential, and entrapment efficiency. The optimized NLCs exhibited a particle size of 275.5 nm, zeta potential of -23.4 mV, PDI of 0.134, and high entrapment efficiencies of 88% for STG and 85% for GPZ. Characterization was performed using FTIR, XRD, DSC, and TEM techniques. In vitro release studies at pH 1.2, 6.8, and 7.4 demonstrated prolonged drug release from the NLCs compared to pure drug solutions. In vivo studies in a nicotinamide-streptozotocin-induced diabetic rat model revealed that STG-GPZ co-loaded NLCs (10/2.5 mg/kg/b.w.) significantly improved pancreatic and liver function histology and exhibited synergistic antihyperglycemic effects. Statistical analysis confirmed the significance of these findings, highlighting the potential of STG-GPZ co-loaded NLCs as an effective oral drug delivery system for T2DM treatment and management. This innovative approach offers a promising solution to enhance therapeutic outcomes for diabetic patients.