Advancement in oral pharmacokinetics of an antibiotic Cefixime using amphiphilic 4-armed macrocyclic surfactant based niosomes

Abstract

The four -armed long carbon chains supramolecular amphiphilic macrocycles are able to self-assemble into nanosized architectures called niosomes that have a membrane bilayer structure. In this study, amphiphilic macrocycle (MCC10) was synthesized by the cyclization of alkylated 4-hydroxybenzaldehyde with resorcinol, in acidic medium acting as a catalyst as well as a solvent, and Cefixime (Cef) was used as model entrapment drug. The drug loaded MCC10 noisomes were characterized by various spectroscopic techniques including; Maldi Toff MS, 1HNMR and FTIR. MCC10 niosomes were subjected to biocompatibility and blood haemolysis using NIH/3T3 cell line and fresh human red blood cells (RBCs), respectively. Acute toxicity study was conducted in mice. The drug loading efficiency was studied by HPLC while shape and size of MCC10 macrocycle was investigated using atomic force microscope (AFM), scanning electron microscopy (SEM) and dynamic light scattering (DLS), respectively. In-vivo oral pharmacokinetic was evaluated in rabbits. The shape of drug loaded macrocycle (Cef-MCC-10) was spherical with average size of 200.1 ± 2.24 nm, and zeta potential −18.0 ± 0.8 mV, having polydispersity index (PDI) of 0.07 and showing greater drug entrapment efficiency (%EE) of 72.86 ± 3.31%. The average size of unloaded vesicles of MCC10 was 157.7 ± 2.02 nm, the zeta potential value for unloaded formulation of MCC10 was −11.5 ± 0.71 mV, and whereas, the polydispersity index was found to be 0.24. MCC10 was screened for cell cytotoxicity study using NIH/3T3 and Hela cells at the highest concentration of 1000 μg/mL where they better cell viability of 71.00 ± 2.10% and 68.00 ± 2.15%, respectively. MCC10 niosomes showed in-vivo drug plasma concentration (Cmax) of10.29 ± 4.81 μg/mL for Cef that was higher than commercially available suspension and capsules. Therefore, MCC10 is presented as effective and safe nano-carrier for Cef to improve the oral pharmacokinetics in rabbits.