Glycoside-based niosomal nanocarrier for enhanced in-vivo performance of Cefixime

Abstract

This study aimed to evaluate the potential of a novel glycoside non-ionic surfactant synthesized and characterized in our laboratory for increased oral bioavailability of Cefixime. The surfactant was synthesized by simple etherification of bergenin with bromoundecane and characterized by 1H NMR and mass spectroscopy (MS). Biocompatibility of the surfactant (BRM-BG) was assessed by in-vitro cytotoxicity against NIH/3T3 cells and human blood hemolysis. In-vivo acute toxicity was evaluated in mices. Cefixime loaded BRM-BG niosomes were investigated for drug entrapment efficiency using HPLC and surface morphology and vesicle size by atomic force microscopy (AFM) and dynamic light scattering (DLS). The in-vivo oral bioavailability and pharmacokinetics studies were carried out using rabbits. Cefixime loaded BRM-BG vesicles were spherical in the size range of 178.66 ± 8.17 nm with a polydipersity index (PDI) of 0.20 ± 0.01, offering an entrapment efficiency as high as 78.4 ± 0.83%. When the surfactant was applied on NIH 3T3 tissue culture, as high as 90.77 ± 3.15% and 86.86 ± 3.02%, cell viability at 1000 μg/mL concentration after 24 and 48 h respectively were observed. The surfactant also caused 5.49 ± 1.62% haemolysis and was found to be safe at a dose up to 2000 mg/kg. In-vivo drug plasma concentration (Cmax) was found to be 9.69 ± 1.22 μg/mL, much higher than that resulting from the intake of commercial suspension and capsules. BRM-BG demonstrated to be safe and effective as carrier of Cefixime following oral dosing in rabbits. The BRM-BG surfactant delivery nano-system is relatively safe and in animal models it is an appropriate carrier for Cefixime, offering enhanced bioavailability compared to commercially available formulations of the drug.