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. 2013:2013:239838.
doi: 10.1155/2013/239838. Epub 2013 Nov 30.

Synthesis, characterization, and acute oral toxicity evaluation of pH-sensitive hydrogel based on MPEG, poly(ε-caprolactone), and itaconic acid

Liwei Tan  1 , Xu Xu  1 , Jia Song  1 , Feng Luo  1 , Zhiyong Qian  1
Affiliations

Synthesis, characterization, and acute oral toxicity evaluation of pH-sensitive hydrogel based on MPEG, poly(ε-caprolactone), and itaconic acid

Liwei Tan et al. Biomed Res Int. 2013.

Abstract

A kind of chemically cross-linked pH-sensitive hydrogels based on methoxyl poly(ethylene glycol)-poly(caprolactone)-acryloyl chloride (MPEG-PCL-AC, PECA), poly(ethylene glycol) methyl ether methacrylate (MPEGMA, MEG), N,N-methylenebisacrylamide (BIS), and itaconic acid (IA) were prepared without using any organic solvent by heat-initiated free radical method. The obtained macromonomers and hydrogels were characterized by ¹H NMR and FT-IR, respectively. Morphology study of hydrogels was also investigated in this paper, and it showed that the hydrogels had good pH-sensitivity. The acute toxicity test and histopathological study were conducted in BALB/c mice. The results indicated that the maximum tolerance dose of the hydrogel was higher than 10,000 mg/kg body weight. No morality or signs of toxicity were observed during the whole 7-day observation period. Compared to the control groups, there were no important adverse effects in the variables of hematology routine test and serum chemistry analysis both in male or female treatment group. Histopathological study also did not show any significant lesions, including heart, liver, lung, spleen, kidney, stomach, intestine, and testis. All the results demonstrated that this hydrogel was nontoxic after gavage. Thus, the hydrogel might be the biocompatible potential candidate for oral drug delivery system.

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Figures

Figure 1
Figure 1
Synthesis scheme of P(ECA-IA-MEG) hydrogel.
Figure 2
Figure 2
Direct observation of synthesis of the P(ECA-IA-MEG) hydrogel. (a) Mixture solution of PECA, IA, MPEGMA, BIS, and APS. (b) Obtained hydrogel after being heated at 37°C for 4 hrs.
Figure 3
Figure 3
1H NMR spectrum of PECA macromonomer (in CDCl3).
Figure 4
Figure 4
FT-IR spectra of PECA and P(ECA-IA-MEG) hydrogels.
Figure 5
Figure 5
SEM observation of P(ECA-IA-MEG) in pH 1.2 (a) and pH 6.8 (b).
Figure 6
Figure 6
Mice body weight of each group during the observation period.
Figure 7
Figure 7
Photograph of mice cardiac muscle, liver, spleen, lung, kidney, stomach, duodenum, jejunum, ileum, colon, and testes after oral administration of P(ECA-IA-MEG) hydrogel (40x), ((b), (d), (f), (h), (j), (l), (n), (p), (r), (t), (v)) and of the control group ((a), (c), (e), (g), (i), (k), (m), (o), (q), (s), (u)).
See this image and copyright information in PMC

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