Acute toxicity evaluation of in situ gel-forming controlled drug delivery system based on biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) copolymer.
In this paper, biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) triblock copolymer was synthesized, and was characterized by FTIR, 1H-NMR and GPC. The PCL-PEG-PCL/dimethyl sulfoxide (DMSO) solution displayed in situ gelling behavior when subcutaneously injected into the body. Toxicity tests and a histopathological study were performed in BALB/c mice. We focused mainly on acute organ toxicity of BALB/c mice by subcutaneous injection. In the acute toxicity test, the dose of subcutaneous injection was 5 g/kg body weight (b.w.), and the mice were observed continuously for 14 days. For the histopathological study, samples including heart, lung, liver, kidneys, spleen, stomach and intestine were histochemically prepared and stained with hematoxylin-eosin for histopathological examination. No mortality or significant signs of toxicity were observed during the whole observation period, and there is no significant lesion to be shown in histopathological study of major organs in the mice. Therefore, the maximal tolerance dose of dimethyl sulfoxide (DMSO) solution of PCL-PEG-PCL copolymer by subcutaneous injection was calculated to be higher than 5 g/kg b.w. Therefore, the PCL-PEG-PCL/DMSO system was thought to be non-toxic after subcutaneous injection, and it might be a candidate for an in situ gelling controlled drug delivery system.
Fang
Fang
F
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China.
Gong
Chang Yang
CY
Dong
Peng Wei
PW
Fu
Shao Zhi
SZ
Gu
Ying Chun
YC
Guo
Gang
G
Zhao
Xia
X
Wei
Yu Quan
YQ
Qian
Zhi Yong
ZY
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001835:Body Weight; D002849:Chromatography, Gas / Q000379:methods; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D016503:Drug Delivery Systems; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry* / Q000633:toxicity; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014018:Tissue Distribution
D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; C492324:poly(epsilon-caprolactone)-poly(oxyethylene)-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; D004121:Dimethyl Sulfoxide