Antileishmanial activity of nano-amphotericin B deoxycholate

• Published in: Journal of antimicrobial chemotherapy 2008-08, Vol.62 (2), p.376-380
• Main Authors: Manandhar, Krishna Das, Yadav, Thakur Prasad, Prajapati, Vijay Kumar, Kumar, Subodh, Rai, Madhukar, Dube, Anuradha, Srivastava, Onkar Nath, Sundar, Shyam
• Format: Article
• Language: English
• Subjects: Amphotericin B - administration & dosage; Amphotericin B - pharmacology; Amphotericin B - therapeutic use; Amphotericin B - toxicity; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiprotozoal Agents - administration & dosage; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; Antiprotozoal Agents - toxicity; Biological and medical sciences; Cell Line; Cricetinae; Deoxycholic Acid - administration & dosage; Deoxycholic Acid - pharmacology; Deoxycholic Acid - therapeutic use; Deoxycholic Acid - toxicity; Drug Combinations; Drug therapy; Human protozoal diseases; in vitro; in vivo; Infectious diseases; Leishmania donovani; Leishmania donovani - drug effects; Leishmaniasis, Visceral - drug therapy; Leshmaniasis; Macrophages - drug effects; Macrophages - parasitology; Medical sciences; Mesocricetus; Mice; nanomedicine; Nanoparticles; Parasites; Parasitic diseases; Pharmacology; Pharmacology. Drug treatments; Protozoal diseases; Spleen - parasitology; visceral leishmaniasis
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn189

Objectives 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 µM) 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 CC50 of 12.67 mg/L in comparison with 10.61 mg/L for amphotericin B, far higher than the doses used for ED50. 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.