Abstract

Introduction: Bile salts have been widely reported as effective edge activators (EA) in nanocarriers due to their ability to enhance membrane fluidity. Their incorporation into nanostructured lipid carriers (NLCs) can increase deformability and improve drug permeation and bioavailability. This study focused on the development of deformable NLCs loaded with a GLP-1 receptor agonist (GLP-1 RA), incorporating sodium deoxycholate (SDC) and sodium deoxyglycocholate (SDGC) as functional excipients. Materials and Methods: NLCs were prepared by a low-energy hot emulsification technique using a blend of solid and liquid lipids and adding SDC or SDGC. Hydrodynamic diameter (HD) and polydispersity index (PdI) were measured by dynamic light scattering; Zeta potential (ZP) by laser Doppler electrophoresis. Deformability was assessed by extrusion through polycarbonate membranes. Transmission Electron Microscopy (TEM) was performed to visualize the NLC morphology. Stability was monitored over four weeks at 4 °C. Encapsulation efficiency (%EE) and drug loading (%DL) were determined by fluorimetry. One-way ANOVA (p < 0.05) was used for statistical analysis. Results: Incorporation of EA significantly reduced the HD from 180.4 nm (control) to 137.2 nm (SDC) and 119.3 nm (SDGC). ZP shifted from -7.20 mV to -28.50 mV, indicating enhanced colloidal stability. Both modified NLCs showed increased deformability compared to control. EE reached 82.4% with a DL of 0.256%. TEM images revealed spherical structures, supporting the role of EA in modulating membrane elasticity. Discussion: Our findings demonstrate that incorporating SDC and especially SDGC improves NLC performance by optimizing HD, ZP, and structural flexibility. These features are advantageous for enhancing buccal permeability and the bioavailability of peptide drugs like GLP-1 RA.