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

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...

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Bibliographic Details
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
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Summary: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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2005.10.030