Development and evaluation of novel itraconazole-loaded intravenous nanoparticles.
The purpose of this study was to present novel intravenous itraconazole-loaded nanoparticles (ITZ-NPs) using human serum albumin (HSA) as drug carrier materials. The ITZ-NPs were prepared by nanoparticle albumin bound technology involving a series of homogenization and lyophilization procedures. The ITZ-NPs powder could be easily reconstituted and provide stable solutions at a wide range of concentrations at 25 degrees C for 24h. In safety test, the ITZ-NPs caused mild hemolysis below the concentration of 10mg/mL and were well tolerated at the dose of 160 mg/kg in mice, indicating better biocompatibility than cyclodextrin formulation of itraconazole (ITZ-CD). The pharmacokinetic parameters of itraconazole and its major metabolite, hydroxyl-itraconazole, of ITZ-NPs had no differences from those of ITZ-CD in mice. For the ITZ-NPs group, the distributions of itraconazole in the lung, liver and spleen were higher than those for ITZ-CD group. It was of significance that ITZ-NPs increased the drug distribution in lung which was always the portal to fungal infection. These results indicate that the ITZ-NPs can be a potential intravenous formulation of itraconazole.
Chen
Wei
W
School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Gu
Bing
B
Wang
Hao
H
Pan
Jun
J
Lu
Weiyue
W
Hou
Huimin
H
D000818:Animals; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005260:Female; D007275:Injections, Intravenous; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012709:Serum Albumin / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D014018:Tissue Distribution; D014961:X-Ray Diffraction
D004337:Drug Carriers; D012709:Serum Albumin; D017964:Itraconazole