Preliminary assessment of the safety evaluation of novel pH-sensitive hydrogel.

In our previous work, a new kind of pH-sensitive hydrogel based on poly (lactic acid) (PLA), methoxyl poly (ethylene glycol) (MPEG) and itaconic acid (IA) was prepared by heat-initiated free radical polymerization without any organic solvent. For further application, the safety of prepared copolymers and hydrogels was evaluated in vitro and in vivo in this paper. In vitro toxicity evaluation of MPEG-PLA-AC (PLE-AC) copolymers included hemolytic test and cytotoxicity which were evaluated by cell viability assay using HEK293 cells. In vivo acute toxicity tests and histopathological study of PLE-AC copolymers were carried out on BALB/c mice which were administrated copolymers (1 g/kg b.w.) intravenously. In acute toxicity test, the mice were observed continuously for 7 days, their body weight obtained everyday, at last the mice were 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. In acute oral toxicity test, mice were orally administered with a total 15 g/kg body weight (b.w.) of P(LE-IA-MEG) 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. All results indicated that the PLE-AC copolymers and pH-sensitive hydrogels were non-toxic. Therefore it might be used as a safe candidate for drug delivery system.