Surface-modified gatifloxacin nanoparticles with potential for treating central nervous system tuberculosis

Patricia Marcianes,1 Sofia Negro,1,2 Luis García-García,3 Consuelo Montejo,4 Emilia Barcia,1,2 Ana Fernández-Carballido1,2 1Department of Pharmaceutics, School of Pharmacy, University Complutense of Madrid, Madrid, Spain; 2Institute of Pharmaceutical Technology, University Complutense of Madrid, Madrid, Spain; 3Multidisciplinary Institute of Cerebral Cartography, University Complutense of Madrid, Madrid, Spain; 4Department of Pharmaceutical and Health Sciences, School of Pharmacy, University CEU-San Pablo, Spain Abstract: A new nanocarrier is developed for the passage of gatifloxacin through the blood–brain barrier to treat central nervous system tuberculosis. Gatifloxacin nanoparticles were prepared by nanoprecipitation using poly(lactic-co-glycolic acid) (PLGA) 502 and polysorbate 80 or Labrafil as surface modifiers. The evaluation of in vivo blood–brain barrier transport was carried out in male Wistar rats using rhodamine-loaded PLGA nanoparticles prepared with and without the surface modifiers. At 30 and 60 minutes after administration, nanoparticle biodistribution into the brain (hippocampus and cortex), lungs, and liver was studied. The results obtained from the cerebral cortex and hippocampus showed that functionalization of rhodamine nanoparticles significantly increased their passage into the central nervous system. At 60 minutes, rhodamine concentrations decreased in both the lungs and the liver but were still high in the cerebral cortex. To distinguish the effect between the surfactants, gatifloxacin-loaded PLGA nanoparticles were prepared. The best results corresponded to the formulation prepared with polysorbate 80 with regard to encapsulation efficiency (28.2%), particle size (176.5 nm), and ζ-potential (-20.1 mV), thereby resulting in a promising drug delivery system to treat cerebral tuberculosis. Keywords: polysorbate 80, Labrafil, gatifloxacin, nanoparticles, targeting, blood–brain barrier, brain delivery