Optimization, in vitro-in vivo evaluation, and short-term tolerability of novel levofloxacin-loaded PLGA nanoparticle formulation

A novel poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation of levofloxacin was developed for multidrug-resistant tuberculosis with the purpose of achieving sustained release in plasma. After lyophilization of levofloxacin-loaded nanoparticles, the average size, charge, and polydispersity index were 268 +/- 18 nm, -10.2 +/- 1.5 mV, and 0.15 +/- 0.03, respectively. The maximum drug encapsulation efficiency and loading capacity were 36.9 +/- 6.1% (w/w) and 7.2 +/- 1.2 mg/100 mg nanopowder, respectively. Biphasic extended-release profile was produced in vitro. Scanning electron microscopy and Fourier transform infrared studies showed spherical shape of drug-loaded nanoparticles and no drugpolymer interactions were observed. After single oral administration in mice, levofloxacin-loaded PLGA nanoparticles produced sustained release of levofloxacin for 4 days in plasma against 24 h for free levofloxacin. Levofloxacin was detected in organs (lung, liver, and spleen) for up to 46 days in case of levofloxacin-loaded nanoparticles, whereas free levofloxacin was cleared within 24 h. This novel formulation did not show any significant adverse effects on body weight and clinical signs in mice. No treatment-related changes were found in hematological and biochemical parameters and on histopathological evaluation. These results indicate the feasibility of development of an orally efficacious safe formulation of levofloxacin with sustained-release properties. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:21652176, 2012