title: Novel chemotherapy for tuberculosis: chemotherapeutic potential of econazole- and moxifloxacin-loaded PLG nanoparticles.
abstract: The potential of econazole (ECZ) and moxifloxacin (MOX) individually against tuberculosis (TB) caused by multidrug-resistant and latent Mycobacterium tuberculosis has been demonstrated. In this study, poly-(dl-lactide-co-glycolide) (PLG) nanoparticle-encapsulated ECZ and MOX were evaluated against murine TB (drug susceptible) in order to develop a more potent regimen for TB. PLG nanoparticles were prepared by the multiple emulsion and solvent evaporation technique and were administered orally to mice. A single oral dose of PLG nanoparticles resulted in therapeutic drug concentrations in plasma for up to 5 days (ECZ) or 4 days (MOX), whilst in the organs (lungs, liver and spleen) it was up to 6 days. In comparison, free drugs were cleared from the same organs within 12-24h. In M. tuberculosis-infected mice, eight oral doses of the formulation administered weekly were found to be equipotent to 56 doses (MOX administered daily) or 112 doses (ECZ administered twice daily) of free drugs. Furthermore, the combination of MOX+ECZ proved to be significantly efficacious compared with individual drugs. Addition of rifampicin (RIF) to this combination resulted in total bacterial clearance from the organs of mice in 8 weeks. PLG nanoparticles appear to have the potential for intermittent therapy of TB, and combination of MOX, ECZ and RIF is the most potent.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Zahoor
authors.initials: Z
authors.lastname: Ahmad
authors.forename: Rajesh
authors.initials: R
authors.lastname: Pandey
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
authors.forename: G K
authors.initials: GK
authors.lastname: Khuller
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D001372:Aza Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple; D004358:Drug Therapy; D004464:Econazole / Q000494:pharmacology / Q000627:therapeutic use*; D024841:Fluoroquinolones; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077266:Moxifloxacin; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001372:Aza Compounds; D004337:Drug Carriers; D024841:Fluoroquinolones; D011108:Polymers; D011804:Quinolines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004464:Econazole; D000077266:Moxifloxacin