Abstract

Bile salts (BS) are identified as EA for their capacity to boost membrane flexibility and deformability of nanocarriers through tight junctions which in turn improves bioavailability of drugs. This study is the first to analyze the incorporation of BS as EA into NLC. Here, we investigated the effect of specific BS (SDC, SDGC, and SDTC) on NLC's physicochemical properties such as hydrodynamic diameter (HD), polydispersity index (PdI), Zeta potential (ZP), and stability. NLCs were synthesized using a blend of solid lipid glycerides, fatty acid esters of PEG, and a mix of capric and caprylic triglycerides, along with different concentrations of BS (2, 6 and, 10 mM) utilizing a modified method combining low-energy hot emulsification with an injection technique. We evaluated HD and PdI using Dynamic Light Scattering and ZP by Laser Doppler Electrophoresis. Stability was assessed over four weeks at 4 °C. In total, 10 NLC syntheses were produced including empty NLCs. One-way ANOVA with p< 0.05 was used to determine statistical significance of observed differences. Our findings revealed a significant impact of BS on the physicochemical properties of NLC. Increasing the concentration of SDC led to a rise in HD, while the inclusion of conjugated BS (SDGC and SDTC) resulted in a decrease. The PdI demonstrated a downward trend as BS concentration increased, indicating that the NLCs were monodisperse systems, attributable to the stabilizing function of BS. Furthermore, a notable increase in value of ZP was observed with the increasing BS concentration, suggesting higher electrostatic repulsion and reduced particle aggregation. The NLC-BS demonstrated high stability, with minimal variation in physicochemical characteristics over four weeks at 4 °C. In conclusion, the incorporation of BS into NLCs led to a general reduction in HD and PdI, an increase in ZP, and high stability over time. These insights can be instrumental in enhancing permeation across biological membranes.