Safety evaluation of amphiphilic three-armed star-shaped copolymer micelles.
In our previous work, we had prepared a biodegradable amphiphilic three-armed star-shaped copolymers (SPCE) based on poly(epsilon-caprolactone) (PCL) and poly(ethylene glycol) (PEG), which could form micelles by self-assembly method and it was a potential carrier for hydrophobic drug. For further application, the safety of SPCE micelles was evaluated in vitro and in vivo here. (13)C-NMR was used to confirm the formation of the micelles in aqueous solution, and the morphology was observed on transmission electron microscope (TEM). Also, thermostability of blank SPCE micelles was determined by Malvern Nano-ZS 90 laser particle size analyzer. In vitro toxicity evaluation included hemolytic test and cytotoxicity. In vivo acute toxicity tests and histopathological study of SPCE micelles were carried out on BALB/C mice which were administrated SPCE micelles (1 g/kg b.w.) intravenously. In acute toxicity test, the mice were observed continuously for 7 days, obtained their body weight every day, at last the mice was sacrificed for the following study: the blood of the mice was assigned for blood chemistry and routine analysis, the heart, liver, spleen, lung, and kidneys were used for histopathological study. All results indicated that the biodegradable self-assembled SPCE micelles were nontoxic; therefore, it might be used as a safe candidate for drug delivery system.
Wang
XiuHong
X
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Kan
Bing
B
Wang
YuJun
Y
Dong
PengWei
P
Shi
Shuai
S
Guo
Gang
G
Zhao
YingLan
Y
Luo
Feng
F
Zhao
Xia
X
Wei
YuQuan
Y
Qian
ZhiYong
Z
D000818:Animals; D002208:Caproates; D016503:Drug Delivery Systems; D005260:Female; D006461:Hemolysis; D007783:Lactones; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D014867:Water
D002208:Caproates; D007783:Lactones; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D014867:Water; C016240:polycaprolactone; D011092:Polyethylene Glycols; C121056:caprolactone