title: Optimization, in vitro-in vivo evaluation, and short-term tolerability of novel levofloxacin-loaded PLGA nanoparticle formulation.
abstract: 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 drug-polymer 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 4-6 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.
authors.affiliation: Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160 012, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kumar
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
authors.forename: Nusrat
authors.initials: N
authors.lastname: Shafiq
authors.forename: Gopal Krishan
authors.initials: GK
authors.lastname: Khuller
authors.forename: Samir
authors.initials: S
authors.lastname: Malhotra
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000737:chemistry*; D064704:Levofloxacin; D051379:Mice; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D015242:Ofloxacin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
chemical_list: D000995:Antitubercular Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D064704:Levofloxacin; D015242:Ofloxacin