Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (16): 2488-2493.doi: 10.3969/j.issn.2095-4344.3114

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Preparation and in vitro evaluation of self-assembling peptide hydrogel loaded with doxorubicin

Zhang Xin1, Lu Ying1, Yao Qingqiang2, Zhu Yishen1   

  1. 1Nanjing Tech University, Nanjing 211816, Jiangsu Province, China; 2Department of Orthopedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
  • Received:2020-02-18 Revised:2020-02-27 Accepted:2020-06-05 Online:2021-06-08 Published:2021-01-07
  • Contact: Yao Qingqiang, Professor, Department of Orthopedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China Zhu Yishen, Professor, The College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, Jiangsu Province, China
  • About author:Zhang Xin, Master, Nanjing Tech University, Nanjing 211816, Jiangsu Province, China
  • Supported by:
    the Key Project of Social Development in Jiangsu Province, No. BE2019736 (to ZYS)

Abstract: BACKGROUND: Chemotherapy is an important method for treating osteosarcoma, but traditional small molecule therapy is not ideal for clinical efficacy and has serious adverse reactions. Therefore, it is necessary to develop a new method for osteosarcoma, which can anti-tumor at low doses and reduce adverse reactions.
OBJECTIVE: To construct a self-assembling peptide hydrogel (SAPH) loaded with doxorubicin (DOX) and analyze its drug release performance and biocompatibility in vitro.
METHODS: DOX was introduced into SAPH composed of FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine), prepared to contain 20, 30, and 40 g/L DOX-SAPH of FEFEFKFK; the DOX mass concentration in this system was 2 g/L. Three kinds of DOX-SAPH were placed in PBS, and the amount of DOX released was regularly detected. Three DOX-SAPH extracts were co-cultured with rabbit bone marrow mesenchymal stem cells, and the cell survival rate was detected by CCK-8 method. The DOX solution containing different concentrations of DOX and the DOX-SAPH extract (containing FEFEFKFK 30 g/L) were co-cultured with MG63 human osteosarcoma cells, and the cell survival rate was detected by CCK-8 method. 
RESULTS AND CONCLUSION: (1) With the increase of the concentration of FEFEFKFK in the hydrogel, the sustained release effect of DOX-SAPH was enhanced. The cumulative drug release rate of DOX-SAPH at 20, 30, and 40 g/L at the 168th hour in vitro was 88%, 83%, and 80%. (2) The cells in 20 g/L DOX-SAPH extract group proliferated faster than 30 and 40 g/L DOX-SAPH extract group at 1, 3, and 5 days in vitro (P < 0.05), in which the 40 g/L DOX-SAPH extract group had certain cytotoxicity on the first day. (3) DOX solution and DOX-SAPH extract showed concentration-dependent inhibition of MG63 cell proliferation, when the concentration of DOX in the DOX solution and the DOX-SAPH extract was lower than 12.5 mg/L, there was no significant difference in the toxicity of the two to MG63 cells (P > 0.05). When the concentration of DOX was higher than 12.5 mg/L, the cell toxicity of the DOX solution was greater than that of DOX-SAPH extract (P < 0.05). (4) The results show that DOX-SAPH has a good drug slow-release effect, which can inhibit the growth of MG63 osteosarcoma cells.

Key words: bone, materials, hydrogel, tumor, doxorubicin, in vitro evaluation, osteosarcoma, tissue engineering

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