Acute oral toxicity evaluation of biodegradable and pH-sensitive hydrogel based on polycaprolactone, poly(ethylene glycol) and methylacrylic acid (MAA).
In this article, a novel biodegradable and pH-sensitive hydrogel based on polycaprolactone, poly(ethylene glycol) and methylacrylic acid (MAA), was prepared by UV-initiated free radical polymerization. The obtained hydrogel was characterized by (1)H NMR and FTIR. The acute toxicity tests and histopathological study were performed in BALB/c mice. In acute oral toxicity test, mice were orally administered with a total 15 g/kg body weight (b.w.) of P(CL-MAA-EG) hydrogels, and were observed continuously for 14 days. For histopathologic study, samples including heart, liver, lung, kidneys, spleen, stomach, and intestine, were histochemically prepared and stained with hematoxylin-eosin for histopathologic examination. No mortality or significant signs of acute toxicity was observed during the whole observation period, and no macroscopic alteration was found in the organs. Histopathological analysis of various organs also did not show any significant pathological changes. Thus, the maximal tolerance dose of P(CL-MAA-EG) hydrogels was calculated to be higher than 15 g/kg b.w. in BALB/c mice. It was suggested that the studied P(CL-MAA-EG) hydrogel in this article were nontoxic after acute oral administration and it might be a promising candidate as a novel oral drug carrier.
Chen
Xian
X
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Qian
ZhiYong
Z
Gou
MaLing
M
Chao
GuoTao
G
Zhang
YangDe
Y
Gu
YingChun
Y
Huang
MeiJuan
M
Wang
JiWei
J
Pan
YiFeng
Y
Wei
YuQuan
Y
Chen
JianPing
J
Tu
MingJing
M
D020341:Absorbable Implants; D000284:Administration, Oral; D000818:Animals; D005260:Female; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
D020100:Hydrogels; D011091:Polyesters; D011109:Polymethacrylic Acids; C016240:polycaprolactone; D011092:Polyethylene Glycols