Novel composite drug delivery system for honokiol delivery: self-assembled poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) micelles in thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) hydrogel.
This study aims to develop a novel composite drug delivery system (CDDS) for hydrophobic honokiol delivery: honokiol loaded micelles in thermosensitive hydrogel (honokiol micelles/hydrogel) based on biodegradable poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers. In our work, we found that PECE copolymers with different molecular weight and PEG/PCL ratios could be administered to form micelles or thermosensitive hydrogel, respectively. Honokiol loaded PECE micelles (honokiol micelles) were prepared by self-assembly of biodegradable PECE copolymer (PEG5000-PCL5000-PEG5000) triggered by its amphiphilic characteristic assisted by ultrasonication without using any organic solvents and surfactants. Meanwhile, biodegradable and injectable thermosensitive PECE hydrogel (PEG550-PCL2400-PEG550) with a lower sol-gel transition temperature at around physiological temperature was also prepared successfully. Furthermore, the obtained honokiol micelles/hydrogel CDDS was a free-flowing sol at ambient temperature and became a nonflowing gel at body temperature. The cytotoxicity results showed that the CDDS was a safe carrier and the encapsulated honokiol retained its potent antitumor effect. In addition, the in vitro release profile demonstrated a significant difference between rapid release of free honokiol and much slower and sustained release of honokiol micelles/hydrogel. The results suggested that the CDDS might have great potential applications in cancer chemotherapy.
Gong
ChangYang
C
State Key Laboratory of Biotherapy, West China Hospital, and School of Life Sciences, Sichuan University, Chengdu, 610041, PR China.
Shi
Shuai
S
Wang
XiuHong
X
Wang
YuJun
Y
Fu
ShaoZhi
S
Dong
PengWei
P
Chen
LiJuan
L
Zhao
Xia
X
Wei
YuQuan
Y
Qian
ZhiYong
Z
D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D020100:Hydrogels / Q000737:chemistry*; D017705:Lignans / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013696:Temperature; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D004337:Drug Carriers; D020100:Hydrogels; D017705:Lignans; D011091:Polyesters; D011092:Polyethylene Glycols; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C016240:polycaprolactone