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pH-responsive hydrogels based on the self-assembly of short polypeptides for controlled release of peptide and protein drugs

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Abstract

In this study, a pH-responsive hydrogel consisting of a 4-arm poly(ethylene glycol)-block-poly(L-glutamic acid) (4a-PEG-PLG) copolymer was developed and used for the controlled release of peptide and protein drugs. It was found that the mechanical properties and degradation processes of the hydrogels could be tuned by changing the polymer concentrations. In vitro drug release results revealed that the release of insulin (or BSA) from hydrogel was highly dependent on the pH, i.e., less than 20% of insulin (or BSA) was released in the artificial gastric fluid (AGF) at 72 h, while close to 100% of insulin (or BSA) was released in the artificial intestinal fluid (AIF). It was because that the deprotonation of carboxyl groups in PLG block caused the disassembly, and even disintegration of the hydrogel in AGF, thereby resulting in accelerated drug release. Circular dichroism spectra showed that the bioactivities of insulin and BSA released from hydrogels were obviously unchanged compared to those of native insulin and BSA, respectively. Mouse fibroblast L929 cells were cultured on the surface of hydrogels and the viabilities of cultured cells were above 90% after incubation for 24 h, indicating that the hydrogels had good cytocompatibilities. Moreover, in vivo degradation evaluation disclosed that the formed hydrogels will completely degrade after 8 days, and the H&E staining study demonstrated the excellent biocompatibility of the as-prepared hydrogels. Therefore, the biocompatible and biodegradable 4a-PEG-PLG hydrogel may serve as a promising platform for pH-responsive drug delivery.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (51520105004 and 51833010) and the Youth Innovation Promotion Association of CAS (2017266).

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Authors and Affiliations

  1. School of Chemistry and Life Science, Changchun University of Technology, Changchun, 130012, China

    Xue Bao & Lijie Duan

  2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Xue Bao, Xinghui Si, Xiaoya Ding & Chunsheng Xiao

  3. University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, China

    Xinghui Si

  4. Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China

    Chunsheng Xiao

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  1. Xue Bao
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  2. Xinghui Si
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  4. Lijie Duan
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  5. Chunsheng Xiao
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Correspondence to Lijie Duan or Chunsheng Xiao.

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Bao, X., Si, X., Ding, X. et al. pH-responsive hydrogels based on the self-assembly of short polypeptides for controlled release of peptide and protein drugs. J Polym Res 26, 278 (2019). https://doi.org/10.1007/s10965-019-1953-8

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