Reduced renal toxicity of nanoparticular amphotericin B micelles prepared with partially benzylated poly-L-aspartic acid.
A partially benzylated poly-L-aspartic acid (PBPA) was synthesized and investigated as a potential renal protective agent for the toxicity of amphotericin B (AmB) when the drug was administered as nanoparticular micelle. Nanoparticular AmB micelles were prepared by slow dialysis of the drug against distilled water at the elevated pH of 11.5 and subsequent sonication with the polymer solution. The resulting nanoparticular AmB micelles with PBPA showed an average diameter of about 20 nm and demonstrated significantly less damage to the tubular cells of the rat's kidney in terms of transmission electron microscopic study. There was little or no damage on the brush border of tubular cells 7 d after single intravenous dose of AmB 5 mg/kg in the rats when the drug was administered as nanoparticuar micelles with PBPA. The reduced renal toxicity appears to be due to the alteration of self-aggregation status of AmB. Molar absorptivity of AmB at 412 nm (a marker for the prevalence of non-aggregated AmB) was significantly higher in the nanoparticular AmB micelles with PBPA than those in AmB micelles without PBPA as well as in Fungizone. This result indicates an association of the reduced nephrotoxicity and the prevalence of non-aggregated AmB. Mechanisms for the reduced renal toxicity may also include the formation of electrostatic complex between anionic groups of PBPA and hydroxyl groups of AmB.
Yoo
Bong Kyu
BK
College of Pharmacy, Yeungnam University, Korea.
Jalil Miah
Md Abdul
MA
Lee
Eung-Seok
ES
Han
Kun
K
D000666:Amphotericin B / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008823:Micelles; D010455:Peptides; C017645:polyaspartate; D000666:Amphotericin B