Self-assembled hydrophobic honokiol loaded MPEG-PCL diblock copolymer micelles.
OBJECTIVE
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(epsilon-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.


CONCLUSIONS
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.
Gou
MaLing
M
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Zheng
XiuLing
X
Men
Ke
K
Zhang
Juan
J
Wang
BiLan
B
Lv
Lei
L
Wang
XiuHong
X
Zhao
YinLan
Y
Luo
Feng
F
Chen
LiJuan
L
Zhao
Xia
X
Wei
YuQuan
Y
Qian
ZhiYong
Z
D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014961:X-Ray Diffraction
D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol