title: Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis.
abstract: OBJECTIVE
  Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized.
  
  
  METHODS
  A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities.
  
  
  RESULTS
  MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC50for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug.
  
  
  CONCLUSIONS
  These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.
authors.affiliation: Department of Pharmacy, Quaid-i-Azam University Islamabad, 45320, Pakistan.|Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Gul
authors.initials: G
authors.lastname: Shahnaz
authors.affiliation: Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Benson J
authors.initials: BJ
authors.lastname: Edagwa
authors.affiliation: Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: JoEllyn
authors.initials: J
authors.lastname: McMillan
authors.affiliation: Department of Entomology, University College of Agriculture & Environmental Sciences, The Islamia University, Bahawalpur, Pakistan.
authors.forename: Sohail
authors.initials: S
authors.lastname: Akhtar
authors.affiliation: Nuclear Medicine, Oncology & Radiotherapy Institute, Islamabad, Pakistan.
authors.forename: Abida
authors.initials: A
authors.lastname: Raza
authors.affiliation: Department of Animal Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Naveeda A
authors.initials: NA
authors.lastname: Qureshi
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, International Islamic University, Islamabad, Pakistan.
authors.forename: Masoom
authors.initials: M
authors.lastname: Yasinzai
authors.affiliation: Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000666:Amphotericin B / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000627:therapeutic use; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles
chemical_list: D000981:Antiprotozoal Agents; D000666:Amphotericin B; D048271:Chitosan; D008358:Mannose
keywords: amphotericin B; macrophage nanoparticle targeting; mannose receptors; thiolated chitosan; visceral leishmaniasis