title: Antileishmanial activity of nano-amphotericin B deoxycholate.
abstract: OBJECTIVE
  The aim of the present study was to compare the efficacy of a nano form of amphotericin B deoxycholate with that of conventional amphotericin B deoxycholate for the treatment of visceral leishmaniasis.
  
  
  METHODS
  We have formulated nanoparticles (10-20 nM) from amphotericin B deoxycholate (1-2 microM) by applying high-pressure (150 argon) milling homogenization and have tested their efficacy in a J774A cell line and in hamsters. Parasite survival and tissue burden in spleen were evaluated for nano-amphotericin B and conventional amphotericin B. Both nano-amphotericin B and conventional amphotericin B were injected intraperitoneally at 5 mg/kg per day for 5 days.
  
  
  RESULTS
  The inhibition of amastigotes in the splenic tissue with nano-amphotericin B was significantly more than with conventional amphotericin B (92.18% versus 74.57%, P = 0.005). Similarly, the suppression of parasite replication in the spleen was also found to be significant (99.18% versus 97.17%, P = 0.05). In a cytotoxicity test, nano-amphotericin B against the J774A cell line had a CC(50) of 12.67 mg/L in comparison with 10.61 mg/L for amphotericin B, far higher than the doses used for ED(50).
  
  
  CONCLUSIONS
  Nanoparticles of amphotericin B had significantly greater efficacy than conventional amphotericin B. This formulation may have a favourable safety profile, and if production costs are low, it may prove to be a feasible alternative to conventional amphotericin B.
authors.affiliation: Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India.
authors.forename: Krishna Das
authors.initials: KD
authors.lastname: Manandhar
authors.forename: Thakur Prasad
authors.initials: TP
authors.lastname: Yadav
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Prajapati
authors.forename: Subodh
authors.initials: S
authors.lastname: Kumar
authors.forename: Madhukar
authors.initials: M
authors.lastname: Rai
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.forename: Onkar Nath
authors.initials: ON
authors.lastname: Srivastava
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002460:Cell Line; D006224:Cricetinae; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D004338:Drug Combinations; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008647:Mesocricetus; D051379:Mice; D053758:Nanoparticles; D013154:Spleen / Q000469:parasitology
chemical_list: D000981:Antiprotozoal Agents; D004338:Drug Combinations; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination