Development of positively charged amphiphile containing self-nanoemulsifying drug delivery system for improved therapeutic efficacy of metronidazole against Helicobacter pylori

Metronidazole (MTZ) has been extensively used to treat bacterial infections for over five decades, but MTZ bacterial resistance has been on the rise, making it less effective against Bacteroides species. This study aimed to improve the antibacterial activity of MTZ-loaded self-emulsifying drug delivery systems (SNEDDS) against H. pylori by the incorporation of alkylated morpholine serving as a positively charged amphiphile. The studies of drug solubility and emulsification led to the development of a ternary phase diagram for selecting formulation ingredients. The key ingredients of the formulation were selected as cinnamon oil (lipid), cremophor EL (sur-factant), and polyethylene Glycol (PEG) 200 (co-surfactant). The optimized formulations were characterized for various physicochemical properties. The average droplet size and zeta potential of MTZ-SNEDDS were deter-mined to be 146.03 & PLUSMN; 2.1 nm and-15.3 & PLUSMN; 0.50 mV while for alkylated morpholine incorporated MTZ-SNEDDS, these were 183.36 & PLUSMN; 21.42 nm and-16.2 & PLUSMN; 1.30 mV, respectively. The thermodynamically robust alkylated morpholine incorporated SNEDDS was successful in maintaining the chemical integrity of the MTZ. The anti-bacterial potential of MTZ-SNEDDS was significantly enhanced against H. pylori upon the incorporation of alkylated morpholine. It can be concluded that incorporating amphiphilic positively charged morpholine into SNEDDS can lead to more intake of them by H. pylori, and prolonging the contact duration of the SNEDDS with the outer membrane of H. pylori increased the transmembrane penetration of SNEDDS.