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.
Qiu
Neng
N
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China.
Cai
Lu-Lu
LL
Xie
Dachun
D
Wang
Guangcheng
G
Wu
Wenshuang
W
Zhang
Yongkui
Y
Song
Hang
H
Yin
Huabin
H
Chen
Lijuan
L
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