Formulating paclitaxel in nanoparticles alters its disposition

Pharm Res. 2005 Jun;22(6):867-74. doi: 10.1007/s11095-005-4581-4. Epub 2005 Jun 8.


Purpose: Paclitaxel is active and widely used to treat multiple types of solid tumors. The commercially available paclitaxel formulation uses Cremophor/ethanol (C/E) as the solubilizers. Other formulations including nanoparticles have been introduced. This study evaluated the effects of nanoparticle formulation of paclitaxel on its tissue distribution.

Methods: We compared the plasma and tissue pharmacokinetics of paclitaxel-loaded gelatin nanoparticles and the C/E formulation. Mice were given paclitaxel-equivalent doses of 10 mg/kg by intravenous injection.

Results: The nanoparticle and C/E formulations showed significant differences in paclitaxel disposition; the nanoparticles yielded 40% smaller area under the blood concentration-time curve and faster blood clearance of total paclitaxel concentrations (sum of free, protein-bound, and nanoparticle-entrapped drug). The two formulations also showed different tissue specificity. The rank order of tissue-to-blood concentration ratios was liver > small intestine > kidney >> large intestine > spleen = stomach > lung > heart for the nanoparticles, and liver > small intestine > large intestine > stomach > lung > or = kidney > spleen > heart for the C/E formulation. The nanoparticles also showed longer retention and higher accumulation in organs and tissues (average of 3.2 +/- 2.3-fold), especially in the liver, small intestine, and kidney. The most striking difference was an 8-fold greater drug accumulation and sustained retention in the kidney.

Conclusions: These data indicate that formulation of paclitaxel affects its clearance and distribution into tissues, with preferential accumulation of nanoparticles in the liver, spleen, small intestine, and kidney.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Area Under Curve
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Ethanol
  • Female
  • Gelatin
  • Indicators and Reagents
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microspheres
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacokinetics*
  • Polyethylene Glycols
  • Solvents
  • Tissue Distribution


  • Antineoplastic Agents, Phytogenic
  • Indicators and Reagents
  • Solvents
  • cremophor
  • Ethanol
  • Polyethylene Glycols
  • Gelatin
  • Paclitaxel