A novel delivery system for amphotericin B with lipid nano-sphere (LNS).
A low-dose therapeutic system with a lipid emulsion for amphotericin B (AmB), a potent antifungal drug, was studied. Lipid nano-sphere (LNS), a small-particle lipid emulsion, was taken up by the liver to a lesser extent than was a conventional lipid emulsion. As a result, LNS yielded higher plasma concentrations of a radiochemical tracer than did the conventional lipid emulsion. LNS was therefore judged to be a suitable carrier for a low-dose therapeutic system for AmB, and LNS incorporating AmB (LNS-AmB) was prepared. LNS-AmB was found to be a homogeneous emulsion with mean particle diameters ranging from 25 to 50 nm. LNS-AmB yielded higher plasma concentrations of AmB than did Fungizone, a conventional intravenous dosage form of AmB, after intravenous administration to mice, rats, dogs, and monkeys. This difference between LNS-AmB and Fungizone was also observed for constant intravenous infusion. In contrast to Fungizone, LNS-AmB showed a linear relationship between dose and AUC. These pharmacokinetic characteristics of LNS-AmB make it a suitable candidate for an effective low-dose therapeutic system for AmB.
Fukui
Hiroshi
H
R&D Administration Department, Nippon Shinyaku Co. Ltd., 14, Nishinosho-Monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan. h.fukui@po.nippon-shinyaku.co.jp
Koike
Tomohiro
T
Saheki
Akira
A
Sonoke
Satoru
S
Seki
Junzo
J
D000666:Amphotericin B / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D004285:Dogs; D004655:Emulsions; D007275:Injections, Intravenous; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008863:Microspheres; D036103:Nanotechnology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000935:Antifungal Agents; D004655:Emulsions; D008081:Liposomes; D000666:Amphotericin B