Thermosensitive Micelles from PEG-Based Ether-anhydride Triblock Copolymers

• Published in: Pharmaceutical research 2010-08, Vol.27 (8), p.1627-1643
• Main Authors: Zhao, Aijun, Zhou, Shaobing, Zhou, Qi, Chen, Tao
• Format: Article
• Language: English
• Subjects: Anhydrides - chemical synthesis; Anhydrides - chemistry; Animals; Antineoplastic Agents - administration & dosage; Biochemistry; biodegradable; Biodegradable materials; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cells, Cultured; Doxorubicin - administration & dosage; Drug Delivery Systems; ether-anhydride; Ethers - chemical synthesis; Ethers - chemistry; General pharmacology; Hep G2 Cells; Humans; Medical Law; Medical sciences; Micelles; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Poloxamer - chemical synthesis; Poloxamer - chemistry; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; polymeric micelles; Polymers; Rats; Research Paper; self-assemble; Temperature; thermo-responsive
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-010-0155-1

Purpose The thermosensitive micelles based on the poly(PEG:CPP:SA) terpolymer composed of poly(ethylene glycol) (PEG), 1,3-bis(carboxyphenoxy) propane (CPP) and sebacic acid (SA) were fabricated for application as a promising drug carrier. Methods The terpolymer can self-assemble into micelles in water by a precipitation technology. The sol-gel transition behaviors were investigated by the tube-tilting method and dynamic rheology. The drug release behaviors were investigated in phosphate-buffered solution (PBS) at 25, 37 and 45°C, respectively, and the tumor cell growth inhibition assays were also evaluated. Results The diameters of these micelles increased as the environmental temperature, and the length of CPP and SA chains increased. The micelles with a low concentration underwent sol-to-nanogel transition as temperature increased from the room temperature to the body temperature, while the polymer solutions with a high concentration underwent sol-to-gel transition as the temperature increased from 20 to 70°C. In vitro release profiles consisted of a burst release followed a sustained release. The cytotoxicity results showed that the terpolymer micelles were biocompatible, and the encapsulated doxorubicin. HCl maintained its potent anti-tumor effect. Conclusion These micelles may bring the ether-anhydride family of polymers great potential as a novel carrier in nanomedicine.