Human plasma distribution of free paclitaxel and paclitaxel associated with diblock copolymers

J Pharm Sci. 1997 Apr;86(4):460-4. doi: 10.1021/js960333n.

Abstract

Amphiphilic diblock copolymer poly (D,L-lactide)-block-methoxy polyethylene glycol was synthesized, and paclitaxel (Taxol) was incorporated into this copolymer above its critical micelle concentration (cmc), resulting in the formation of polymeric micellar paclitaxel (PMT). Free paclitaxel dissolved in acetonitrile (TAX) and PMT, at 10 micrograms of paclitaxel/mL of human plasma, were incubated for 5, 30, and 60 min at 37 degrees C. Following incubation, the plasma was separated into its high-density (HDL), low-density (LDL), very-low-density (VLDL) lipoprotein and lipoprotein-deficient (LPDP) plasma fractions by density gradient ultracentrifugation. Each of these lipoprotein (LP) and LPDP fractions were analyzed for paclitaxel and plasma lipid levels by well-established HPLC and enzymatic assays. When TAX was incubated in human plasma for 5 min, an equal amount of drug was found in the LP and LPDP fractions. This distribution profile did not change following incubation for 30 and 60 min. Of the amount of TAX that was distributed within the LP fraction, 70-75% of TAX was associated with the HDL fraction for all time points studied. The paclitaxel plasma and LP distribution profile for PMT was similar to the distribution profile of TAX, suggesting that the plasma and LP distribution of paclitaxel is independent of the method of paclitaxel delivery and that LP distribution is not a function of mass lipid levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / blood*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Humans
  • Lipids / blood
  • Paclitaxel / blood*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacokinetics
  • Polyesters / chemistry
  • Polyethylene Glycols / chemistry
  • Polymers

Substances

  • Antineoplastic Agents, Phytogenic
  • Lipids
  • Polyesters
  • Polymers
  • Polyethylene Glycols
  • poly(lactide)
  • monomethoxypolyethylene glycol
  • Paclitaxel