Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel: part 1--Synthesis, characterization, and acute toxicity evaluation.
In this work, biodegradable PCL-PEG-PCL (PCEC) triblock copolymers were successfully synthesized at one-step. Aqueous solution of PCEC copolymer displayed thermosensitive sol-gel-sol transition behavior, which is flowing sol at low temperature and turns into non-flowing gel at body temperature. The cytotoxicity of PCEC copolymer was evaluated by cell viability assay using HEK293 and WISH cells. In vivo gel-formation, degradation test, acute toxicity tests, and histopathological study of PCEC hydrogels were performed in BALB/c mice by subcutaneous administration. In acute toxicity test, the mice were observed continuously for 21 days. For histopathologic study, samples including heart, liver, spleen, lung, kidneys, and tissue of injection site were histochemical prepared and stained with hematoxylin-eosin. No mortality or significant signs of acute toxicity was observed during the whole observation period and there is no significant lesion to be shown in histopathologic study of major organs and tissue of injection site. The maximum tolerance dose (MTD) of PCEC hydrogel (20 wt%) by subcutaneous administration was calculated to be higher than 25 g/kg b.w. The results indicated that the obtained PCEC hydrogel was non-toxic after subcutaneous administration, and could be a safe candidate for in situ gel-forming controlled drug delivery system.
Gong
Chang Yang
CY
State Key Laboratory of Biotherapy, West China Hospital, and School of Life Sciences, Sichuan University, Chengdu 610041, China.
Shi
Shuai
S
Dong
Peng Wei
PW
Yang
Bing
B
Qi
Xiao Rong
XR
Guo
Gang
G
Gu
Ying Chun
YC
Zhao
Xia
X
Wei
Yu Quan
YQ
Qian
Zhi Yong
ZY
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005260:Female; D005947:Glucose / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity*; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared
D003692:Delayed-Action Preparations; D020100:Hydrogels; D011091:Polyesters; D012996:Solutions; C515340:poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; D005947:Glucose