Preparation and in vitro evaluation of self-assembling peptide hydrogel loaded with doxorubicin / 中国组织工程研究

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). 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.