Injectable And Biodegradable PH-Responsive Hydrogels For Localized And Sustained Treatment Of Human Fibrosarcoma

Objective:In order to overcome a short time, toxic and side effect in circulation in the chemical treatment of human fibrosarcoma. We designed and synthesized a novel injectable and Biodegradable pH-Responsive dynamic hydrogels which load common chemotherapy drug doxorubicin(DOX) then we evaluate its efficacy in the treatment of human fibrosarcoma..Methods:In this study, we designed and synthesized a new injectable hydrogel based on hydrogel precursors named polyethylene glycol(PEG) dialdehyde and α, β-polyaspartylhydrazide, meanwhile, evaluated the gel system formed in situ. In the reaction, acylhydrazone bonds have been successfully utilized. We synthetic hydrogel precursors, Dibenzaldehyde-Terminated PEG(DF-PEG) and Polyaspartylhydrazide(PAHy). We study the structure and properties of the hydrogels and test its biodegradation, tissue compatibility and in vivo gelation. We design it as drug carrier, load chemotherapy drugs doxorubicin for the treatment of bearing mice with human fibrosarcoma and evaluate the effect of the tumor chemical therapy..Results: An injectable poly(? α,β-L-aspartic acid)-based hydrogel via hydrazone crosslinking strategy was also studied in this thesis. The gelation occurs under physiological conditions immediately upon mixing of the two aqueous without any crosslinkers, initiators and residual catalysts. By scanning electron microscope, the internal structure of the hydrogel was porous. The degradation behavior of the hydrogel was found, the crosslinked structure of the hydrogel became loose with the decrease of pH, which showed that the hydrogel had good degradation properties. The loading and release behavior of the drug in the hydrogel with hydrophilic doxorubicin hydrochloride as the model drug were studied. In the acidic environment, the release rate of DOX was significantly higher than that in the neutral environment. Finally, we use hydrogel load DOX to treat BALB / c mouse with human fibrosarcoma. the therapeutic effect of drugs was observed. 20 days later, mice were dissected and we found that in the treatment group(hydrogel load DOX) compared with the control group(treated with DOX), tumor tissue volume significantly reduced.Conclusion: 1The gelation occurs under physiological conditions immediately upon mixing the two aqueous poly(? α,β-L-aspartic acid and DF-PEG) without any crosslinkers, initiators and residual catalysts. 2 The hydrogel has a good pH response, biocompatibility, degradation and the process of cross-linked structure showed pH dependent. 3 The hydrogel can be used as a carrier, realise drug sustained release, and shows excellent in the treatment of human fibrosarcoma.