title: Peroral amphotericin B polymer nanoparticles lead to comparable or superior in vivo antifungal activity to that of intravenous Ambisome® or Fungizone™.
abstract: BACKGROUND
  Despite advances in the treatment, the morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70-90%) in immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation; development of an oral formulation would be beneficial as well as economical.
  
  
  METHODS
  Poly(lactide-co-glycolode) (PLGA) nanoparticles encapsulating AMB (AMB-NPs) were developed for oral administration. The AMB-NPs were 113 ± 20 nm in size with ~70% entrapment efficiency at 30% AMB w/w of polymer. The in vivo therapeutic efficacy of oral AMB-NPs was evaluated in neutropenic murine models of disseminated and invasive pulmonary aspergillosis. AMB-NPs exhibited comparable or superior efficacy to that of Ambisome® or Fungizone™ administered parenterally indicating potential of NPs as carrier for oral delivery.
  
  
  CONCLUSIONS
  The present investigation describes an efficient way of producing AMB-NPs with higher AMB pay-load and entrapment efficiency employing DMSO as solvent and ethanol as non-solvent. The developed oral formulation was highly efficacious in murine models of disseminated aspergillosis as well as an invasive pulmonary aspergillosis, which is refractory to treatment with IP Fungizone™ and responds only modestly to AmBisome®.
authors: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors: Jagdishbhai L
authors: JL
authors: Italia
authors: Andrew
authors: A
authors: Sharp
authors: Katharine C
authors: KC
authors: Carter
authors: Peter
authors: P
authors: Warn
authors: M N V Ravi
authors: MN
authors: Kumar
mesh_terms: D000096:Acetone / Q000737:chemistry; D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D007275:Injections, Intravenous; D055744:Invasive Pulmonary Aspergillosis / Q000188:drug therapy; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D011108:Polymers; D012997:Solvents; C068538:liposomal amphotericin B; D000096:Acetone; D000666:Amphotericin B; D004121:Dimethyl Sulfoxide