Pharmacokinetics of Levofloxacin Entrapped in Non-Ionic Surfactant Vesicles (Niosomes) in Sprague Dawley Rats.

Abstract

Background/Objectives: Bacteria are becoming increasingly resistant to levofloxacin and other fluoroquinolones. Previously, drug loading in colloidal carriers has shown enhanced penetration into and retention in bacterial cells. However, the mechanism of levofloxacin niosomes' bio-disposition in rats has not been reported. This study investigated the pharmacokinetics (PK) of optimized levofloxacin niosomes following intraperitoneal injection into Sprague Dawley rats. Methods: Formulation and processing variables settings were determined using DoE Fusion One software. The resulting data input into the Optimizer module provided niosome formulation for in vivo study in Sprague Dawley rats. Each group of rats (n = 6) was injected intraperitoneally with either conventional levofloxacin or its niosomes at equivalent doses of 7.5 mg/kg/dose. Blood samples were collected via tail snip and analyzed using a validated HPLC method. The plasma-time data were fed into the Gastroplus software (Simulations Plus, CA) and used to model levofloxacin PK. Results: Niosomes for in vivo study had a mean hydrodynamic diameter of 329.16 nm (±18.0), encapsulation efficiency (EE) of 30.74%, Zeta potential of 21.72 (±0.54), and polydispersity index (PDI) of 0.286 (±0.014). Both the Akaike and Schwarz criteria showed levofloxacin niosomes and conventional drug formulation obeying one- and two-compartment PK models, respectively. Thus, formulation in niosomes altered levofloxacin biodistribution by concentrating the drug in the vascular compartment. Conclusions: Niosome encapsulation of levofloxacin altered its biodistribution and pharmacokinetic profile, possibly by protecting i.p. levofloxacin en route into plasma, and significantly enhanced its plasma concentration with enhanced potential for treating intravascular infections.