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

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.

• Authors: Masato Watanabe, Kumi Kawano, Masayuki Yokoyama, Praneet Opanasopit, Teruo Okano, Yoshie Maitani
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 308 Issue 1-2 Pg. 183-9 (Feb 03 2006) ISSN: 0378-5173 [Print] Netherlands
• PMID: 16324807 (Publication Type: Journal Article)

Chemical References

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

Topics

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