Potential Active Targeting of Gatifloxacin to Macrophages by Means of Surface-Modified PLGA Microparticles Destined to Treat Tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and represents one of the leading causes of mortality worldwide due to multidrug-resistant TB (MDR-TB). In our work, a new formulation of biodegradable PLGA microparticles was developed for pulmonary administration of gatifloxacin, using a surface modifier agent to actively target alveolar macrophages thereby allowing to gain access of the drug to Mycobacterium tuberculosis. For this, rapid uptake of the particles by macrophages is beneficial. This process was evaluated with fluorescein-loaded microparticles using PLGA 502 or PLGA 502H as polymers and labrafil as surface modifier. Cell phagocytosis was studied in raw 264.7 mouse macrophage cell line after 3, 5, 24, and 48 h incubation with the microparticles. Labrafil enhanced the uptake rate of PLGA 502H microparticles by macrophages which was directly related to the modification of the polymer matrix. Gatifloxacin-loaded PLGA microparticles using PLGA 502 or PLGA 502H and labrafil were prepared. From our results, only microparticles prepared with PLGA 502H and labrafil exhibited high encapsulation efficiency (89.6 ± 0.2%), rapid phagocytosis by macrophages (3 h), and remained inside the cells for at least 48 h, thereby resulting in a suitable carrier to potentially treat MDR-TB.

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

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.