Transfersomal nanoparticles for nose-to-brain delivery of ofloxacin for better management of bacterial meningitis: Formulation, optimization by Box-Behnken design, characterization and in vivo pharmacokinetic study

Abstract This study aims to formulate a nanosystem of ofloxacin (OFLOX) for nose-to-brain delivery to enhance brain accumulation and improve management of bacterial meningitis. OFLOX loaded transfersomal nanoparticles (OFLOX-TNPs) were prepared by a thin film hydration technique. A Box-Behnken design was employed to investigate the influence of Lipid concentration, Edge Activator concentration, and Cholesterol amount on particle size, entrapment efficiency, and intranasal permeation. Lipid concentration (%w/v) of 5%, Edge Activator concentration (%w/w) of 14.6%, and cholesterol amount (mg) of zero produced 271.5 nm particles entrapping 79.3% of the total drug added. Percentage of OFLOX released from the optimized nanoparticles was 75.39%, and 78.7% of the drug permeated after 24 h. Histopathological investigation displayed that the optimal formula in an in situ gel is tolerable. Pharmacokinetic study showed that the brain blood ratios of OFLOX from intravenous solution, intranasal solution, and intranasal OFLOX-TNPs in an in situ gel were 0.305, 0.579, and 1.858 respectively at 30 min. It is concluded that nanotransfersomes loaded with OFLOX could be a promising colloidal drug delivery system for effective brain targeting and treatment of bacterial meningitis. However, preclinical and clinical investigations are essential to evaluate its efficacy in humans.