Preparation and Characterization of a Nanostructured Lipid Carrier-Based Formulation of Pioglitazone for Enhanced Antidiabetic Activity

Abstract

Pioglitazone, a thiazolidinedione class antidiabetic agent, suffers from low aqueous solubility and suboptimal bioavailability, which limits its therapeutic potential. The present study aimed to develop and characterize a nanostructured lipid carrier (NLC)-based formulation of pioglitazone to enhance its solubility, stability, and antidiabetic efficacy. Nanostructured lipid carriers were prepared using the hot homogenization and ultrasonication technique, employing solid lipids (glyceryl monostearate), liquid lipids (oleic acid), and surfactants (Tween 80 and soy lecithin). The formulation was optimized based on particle size, polydispersity index (PDI), zeta potential, drug loading, and entrapment efficiency. Characterization techniques included dynamic light scattering (DLS) for size analysis, transmission electron microscopy (TEM) for morphological studies, and differential scanning calorimetry (DSC) and X-ray diffraction (XRD) to investigate the crystalline nature of the drug. In vitro drug release studies were performed using the dialysis bag method. The antidiabetic potential was evaluated in streptozotocin-induced diabetic rats compared to plain pioglitazone suspension. The optimized NLC formulation exhibited a mean particle size of 152.6 ± 5.8 nm, PDI of 0.212, and zeta potential of –26.4 mV, indicating good stability. The entrapment efficiency and drug loading were found to be 89.7% and 8.2%, respectively. TEM images confirmed spherical morphology with uniform dispersion. DSC and XRD studies indicated molecular dispersion of pioglitazone in the lipid matrix. The NLC formulation showed a sustained release profile over 24 hours. In vivo studies demonstrated significantly improved glycemic control in diabetic rats treated with NLCs compared to the conventional formulation (p < 0.01). The nanostructured lipid carrier system effectively enhanced the physicochemical properties and antidiabetic efficacy of pioglitazone. This novel delivery platform holds promise for improving the therapeutic outcomes of poorly water-soluble antidiabetic drugs.