Superior chemotherapeutic efficacy of amphotericin B in tuftsin-bearing liposomes against Leishmania donovani infection in hamsters.
Chemotherapeutic efficacy of the amphotericin B (Amp B), which is the drug of choice for treatment of the leishmanial infections (kala-azar) that become resistant to the conventional chemotherapy using antimonials, has been examined in the Leishmania donovani infected hamsters after encapsulating the drug in tuftsin-free as well as tuftsin-bearing liposomes. The activity was significantly increased (p < 0.05) by delivering Amp B in tuftsin-free liposomes. This antileishmanial effect of the liposomized Amp B was further increased (p < 0.05) by grafting the natural macrophage-activator tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), on the liposome's surface. This could possibly be attributed to both the enhanced drug tolerance after liposomization as well as to the increased uptake of tuftsin-bearing Amp B-laden liposomes by the macrophages. In addition to the increased efficacy, encapsulation of Amp B in the tuftsin-bearing liposomes also enhanced the drug accessibility to areas (e.g. bone marrow) that are otherwise inaccessible to the free drug. These results further demonstrate the usefulness of tuftsin-bearing liposomes as drug vehicles in treatment of the macrophage-based infections that have been reviewed recently (Agrawal, A.K. and Gupta, C.M. (2000). Tuftsin-bearing liposomes in treatment of macrophage-based infections, Adv. Drug Deliv. Rev., 41, 135-146).
Agrawal
Ajay K
AK
Central Drug Research Institute, Lucknow, India. ajay224@hotmail.com
Agrawal
A
A
Pal
A
A
Guru
P Y
PY
Gupta
C M
CM
D000666:Amphotericin B / Q000008:administration & dosage* / Q000627:therapeutic use*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D006224:Cricetinae; D004337:Drug Carriers; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008081:Liposomes; D008264:Macrophages / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D014405:Tuftsin / Q000737:chemistry*
D000981:Antiprotozoal Agents; D004337:Drug Carriers; D008081:Liposomes; D000666:Amphotericin B; D014405:Tuftsin