Design and development of lipid modified arginine based self-nanoemulsifying drug delivery systems for improved antibacterial activity of cefixime against S. aureus and E. coli

Cefixime (CEF) has numerous potential applications in the treatment of bacterial infections. However, due to its decreased cellular internalization, poor aqueous solubility, rapid intestinal hepatic metabolism, its clinical efficacy is limited. The purpose of this research was to develop an amphiphilic arginine (Amp-ARG) containing self-nanoemulsifying drug delivery system (SNEDDS) acting as a positively charged amphiphile for enhancing the antibacterial properties of CEF against E. coli and S. aureus. The self-emulsifying characteristics of various oils, including essential oils, were investigated using suitable surfactants and co-surfactants. Because of their high CEF solubilizing potential, transcutol (R) Hp, labrasol, and cinnamon oil were selected as co-surfactant, surfactant, and oil respectively, to develop the formulation of SNEDDs. The composition of the selected constituents was optimized via ternary phase diagram and the developed CEF loaded SNEDDS (CEF-SNEDDS) and Amp-ARG containing CEF-SNEDDS were investigated for morphological evaluation, droplet size, polysispersity index and zeta potential value. The developed SNEDDS was discovered to be extremely stable, having a spherical surface morphology and a nano range size. Furthermore, the CEF antibacterial activity was increased upon loading in the optimized SNEDDS. Interestingly, a significant antibacterial effect was observed for ARG-CEF-SNEDDS against both the investigated bacterial strains, including S. aureus and E. coli, owing to comparatively improved internalization of CEF mediated by the electrostatic interaction of the Amp-ARG polar head with the bacterial cell, followed by interaction with membrane lipid bilayers via their hydrophobic alkyl chain. Hence, the observed findings revealed the potential of the developed ARG-CEF-SNEDDS to be used as an effective candidate for bacterial infections.