Preparation of camptothecin-loaded polymeric micelles and evaluation of their incorporation and circulation stability

Int J Pharm. 2006 Feb 3;308(1-2):183-9. doi: 10.1016/j.ijpharm.2005.10.030.

Abstract

To improve its aqueous solubility and stability in biological fluid, CPT was physically loaded in polymeric micelles. Polymeric micelles were composed of various poly(ethylene glycol)-poly(aspartate ester) block copolymers (PEG-P(Asp(R))). The incorporation and circulation stability of CPT micelles were evaluated by measuring the CPT in micelle using gel-permeation chromatography and by CPT concentration measurement after intravenous injection using HPLC, respectively, in terms of chemical structure of block copolymers. The stability of CPT-loaded micelles in vivo depended on the amount of benzyl esters, and length of PEG in the polymers to a greater degree than it did in vitro. A stable formulation of CPT-loaded micelles was obtained using PEG-P(Asp) with PEG of 5,000 (MW), 27 Asp units, and 57-75% benzyl esterification of Asp residue. This CPT-loaded micelles showed about a 17-fold lower blood clearance value than unstable micelles. The CPT-loaded micelles are potentially delivered to tumor sites owing to an extended circulation in the blood stream.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Area Under Curve
  • Aspartic Acid / chemistry
  • Biopolymers / chemistry
  • Camptothecin / administration & dosage
  • Camptothecin / chemistry
  • Camptothecin / pharmacokinetics*
  • Drug Carriers
  • Drug Stability
  • Injections, Intravenous
  • Male
  • Mice
  • Micelles*
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry*
  • Solubility

Substances

  • Antineoplastic Agents, Phytogenic
  • Biopolymers
  • Drug Carriers
  • Micelles
  • Polymers
  • poly(ethylene oxide)-block-poly(beta-benzyl aspartate)
  • Aspartic Acid
  • Polyethylene Glycols
  • Camptothecin