Brain targeting of cefepime loaded transfersomes based thermosensitive in situ gel via intranasal delivery: In vitro and in vivo studies

Abstract

In the present study, cefepime loaded transfersomes based in situ gel (CFP-TSFG) were developed for brain targeting via intranasal delivery. Cefepime loaded transfersomes (CFP-TSFs) prepared by thin film hydration method. Box–Behnken design was applied for optimization by analyzing the effect of independent variables i.e., phospholipon 90G, tween-80, and cefepime on particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimized CFP-TSFs formulation was found to be spherical shaped with PS 111.1±0.6nm, PDI 0.28±0.05, ZP -27±0.9mV, EE 84±0.3%, and deformability index 73±0.3. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction technique (XRD), were performed to analyze the chemical interactions and crystallinity of excipients and formulation respectively. CFP-TSFs were effectively loaded in optimized thermosensitive in situ gel. CFP-TSFG was evaluated for its physicochemical properties, in vitro, antimicrobial, ex vivo, and in vivo studies. In vitro studies showed sustained behavior of CFP-TSFG. Ex vivo permeation studies of CFP-TSFG showed 34-fold increased permeation compared to conventional gel. In vivo studies demonstrating improved targeting efficiency of developed CFP-TSFG via the intranasal route. The biocompatibility of the CFP-TSFG was evaluated and confirmed by toxicity studies. In conclusion, the optimized CFP-TSFG system could be a potential formulation for brain targeting via intranasal delivery.