title: Evaluation of toxicity & therapeutic efficacy of a new liposomal formulation of amphotericin B in a mouse model.
abstract: OBJECTIVE
  Current therapy for leishmaniasis is limited and unsatisfactory. Amphotericin B, a second-line treatment is gradually replacing antimonials, the first-line treatment and is used as the preferred treatments in some regions. Though, presently it is the only drug with highest cure rate, its use is severely restricted by its acute toxicity. In the present study novel lipid-amphotericin B formulations with lower toxicity than the parent drug were evaluated for the treatment of visceral leishmaniasis (VL) in a mouse model.
  
  
  METHODS
  The toxicity and therapeutic efficacy of a new amphiphilic formulation of amphotericin B (Kalsome10) was compared to that of amphotericin B deoxycholate (Fungizone) in a mouse model of VL using quantitative real-time PCR (qRT-PCR).
  
  
  RESULTS
  The toxicity of amphotericin B was significantly less with liposomal formulation as compared to the deoxycholate form, evidenced by reduced nephrotoxicity and higher tolerated dose in BALB/c mice. The therapeutic efficacy was evaluated by quantitative real time (RT) PCR using primers highly specific for the ITS region of Leishmania donovani. There was reduction in parasite load by 2 log unit after 7 days of treatment and finally resulting in complete clearance of parasite from infected mice after 30 days of treatment with Kalsome10.
  
  
  CONCLUSIONS
  This new formulation showed a favourable safety profile and better efficacy when compared to conventional amphotericin B. If production cost is kept low, it may prove to be a feasible alternative to conventional amphotericin B.
authors.affiliation: Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Mishra
authors.forename: Ayan
authors.initials: A
authors.lastname: Dey
authors.forename: Niti
authors.initials: N
authors.lastname: Singh
authors.forename: Ramesh
authors.initials: R
authors.lastname: Somvanshi
authors.forename: Sarman
authors.initials: S
authors.lastname: Singh
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000473:pathology; D008081:Liposomes / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D008081:Liposomes; D000666:Amphotericin B