Synthesis, structural and in vitro studies of well-dispersed monomethoxy-poly(ethylene glycol)-honokiol conjugate micelles.
Honokiol, an active principle extracted from Magnolia officinalis, has great potential as a cancer treatment. However, its poor water solubility greatly hampers its delivery to the tumor sites at an effective concentration. In this study, an amphiphilic polymer-drug conjugate was successfully prepared by condensation of low molecular weight monomethoxy-poly(ethylene glycol) (MPEG)-2000 with honokiol (HK) through an ester linkage to increase the hydrophilicity of honokiol. The MPEG-honokiol (MPEG-HK) conjugate prepared formed nano-sized micelles, with a mean particle size of less than 20 nm (MPEG-HK, 360 µg ml(-1)) in water, which could be well dispersed in water. The nanoparticles obtained were characterized by particle size distribution, morphology and zeta potential. The stability and hydrolysis profile of the polymeric pro-drug in phosphate-buffered saline (PBS) and plasma were also studied and the results showed that only 20% of the conjugated honokiol was released in 2.0 h in beagle dog plasma, while in PBS the time required to reach 20% of honokiol release was >200 h. Meanwhile, the inhibitory activity of the honokiol conjugate was found to be retained in vitro against LL/2 cell lines with an IC50 value of 10.7 µg ml(-1). These results suggest that the polymer-drug conjugate provides a potential new approach to hydrophobic drugs, such as honokiol, in formulation design.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China.
Neng
N
Qiu
Lu-Lu
LL
Cai
Dachun
D
Xie
Guangcheng
G
Wang
Wenshuang
W
Wu
Yongkui
Y
Zhang
Hang
H
Song
Huabin
H
Yin
Lijuan
L
Chen
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000737:chemistry*; D003102:Colloids / Q000737:chemistry; D004058:Diffusion; D004285:Dogs; D004339:Drug Compounding / Q000379:methods; D017705:Lignans / Q000008:administration & dosage / Q000737:chemistry*; D008422:Materials Testing; D008823:Micelles; D053769:Nanocapsules / Q000737:chemistry* / Q000627:therapeutic use; D010316:Particle Size; D010949:Plasma / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D000498:Allyl Compounds; D010636:Phenols
D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D003102:Colloids; D017705:Lignans; D008823:Micelles; D053769:Nanocapsules; D011092:Polyethylene Glycols; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C028210:monomethoxypolyethylene glycol