Highly effective oral amphotericin B formulation against murine visceral leishmaniasis.
Visceral leishmaniasis is a deadly parasitic disease caused by obligate intramacrophage protozoans of the Leishmania genus. The World Health Organization estimates the annual death toll to be 50,000, with 500,000 new cases each year. Without treatment, visceral leishmaniasis is inevitably fatal. For the last 70 years, the first line of defense has been pentavalent antimonials; however, increased resistance has brought amphotericin B to the forefront of treatment options. Unfortunately, the difficult route of drug administration, toxicity issues, and cost prevent amphotericin B from reaching the infected population, and mortality continues to rise. Our reformulation of amphotericin B for oral administration has resulted in a highly efficacious antileishmanial treatment that significantly reduces or eradicates liver parasitemia in a murine model of visceral leishmaniasis. This formulation has overcome amphotericin B's significant physicochemical barriers to absorption and holds promise for the development of a self-administered oral therapy for the treatment of visceral leishmaniasis.
Wasan
Kishor M
KM
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3. kwasan@interchange.ubc.ca
Wasan
Ellen K
EK
Gershkovich
Pavel
P
Zhu
Xiaohua
X
Tidwell
Richard R
RR
Werbovetz
Karl A
KA
Clement
John G
JG
Thornton
Sheila J
SJ
D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008099:Liver / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000188:drug therapy; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine; D000666:Amphotericin B