Self-Assembled Hydrophobic Honokiol Loaded MPEG-PCL Diblock Copolymer Micelles

• Published in: Pharmaceutical research Vol. 26; no. 9; pp. 2164 - 2173
• Main Authors: Gou, MaLing, Zheng, XiuLing, Men, Ke, Zhang, Juan, Wang, BiLan, Lv, Lei, Wang, XiuHong, Zhao, YinLan, Luo, Feng, Chen, LiJuan, Zhao, Xia, Wei, YuQuan, Qian, ZhiYong
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.09.2009; Springer US; Springer; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Biotechnology; Cancer; Chemotherapy; Chromatography, Gel; Chromatography, High Pressure Liquid; General pharmacology; Herbal medicine; Medical Law; Medical sciences; Micelles; Microscopy, Electron, Transmission; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Polyesters - chemistry; Polyethylene Glycols - chemistry; Polymers; Rats; Rats, Sprague-Dawley; Research Paper; X-Ray Diffraction; Micelle; MPEG-PCL; self-assembly; nanomedicine; honokiol; Performance evaluation; Pharmaceutical technology; Diblock copolymer; Technique; Nanotechnology
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-009-9929-8

Purpose Honokiol showed potential application in cancer treatment, but its poor water solubility restricts its clinical application greatly. So, we designed a self-assembled monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelle to load honokiol to overcome its poor water solubility. Methods We synthesized MPEG-PCL diblock copolymer that could self-assemble into monodisperse micelles at the particle size of ca.18 nm in water. Honokiol was loaded into MPEG-PCL micelle by direct dissolution method assisted by ultrasound, without any surfactants, organic solvents, and vigorous stirring. Results The blank MPEG-PCL micelles (100 mg/mL) did not induce any hemolysis in vitro and showed very low toxicity ex vivo and in vivo. Honokiol could be molecularly incorporated into MPEG-PCL micelles at the drug loading of about 20% by direct dissolution method assisted by ultrasound. After loaded into MPEG-PCL micelles, honokiol maintained its molecular structure and anticancer activity in vitro. Honokiol could be sustained released from MPEG-PCL micelles in vitro. The honokiol loaded MPEG-PCL micelles could be lyophilized without any adjuvant. Conclusion The prepared honokiol formulation based on self-assembled MPEG-PCL micelle was stable, safe, effective, easy to produce and scale up, and showed potential clinical application.