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

• Published in: International journal of pharmaceutics 2006-02, Vol.308 (1), p.183-189
• Main Authors: Watanabe, Masato, Kawano, Kumi, Yokoyama, Masayuki, Opanasopit, Praneet, Okano, Teruo, Maitani, Yoshie
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacokinetics; Area Under Curve; Aspartic Acid - chemistry; Biological and medical sciences; Biopolymers - chemistry; Camptothecin; Camptothecin - administration & dosage; Camptothecin - chemistry; Camptothecin - pharmacokinetics; Drug Carriers; Drug Stability; General pharmacology; In vivo stability; Injections, Intravenous; Long circulating; Male; Medical sciences; Mice; Micelles; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Polymeric micelles; Polymers - chemistry; Solubility
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2005.10.030

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 5000 (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.