A novel delivery system for amphotericin B with lipid nano-sphere (LNS)

Int J Pharm. 2003 Oct 20;265(1-2):37-45. doi: 10.1016/s0378-5173(03)00404-6.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Amphotericin B / administration & dosage*
  • Amphotericin B / blood
  • Amphotericin B / pharmacokinetics
  • Animals
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / blood
  • Antifungal Agents / pharmacokinetics
  • Area Under Curve
  • Dogs
  • Emulsions
  • Injections, Intravenous
  • Liposomes
  • Liver / metabolism
  • Macaca fascicularis
  • Male
  • Mice
  • Mice, Inbred Strains
  • Microspheres
  • Nanotechnology
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution

Substances

  • Antifungal Agents
  • Emulsions
  • Liposomes
  • Amphotericin B