Fabrocation And Applications Of Nanogel-Incorporated Injectable Hydrogel

The biocompatible hydrogels have been widely used in biomedical research,especially as a drug delivery system due to their high drug loading capability with sustained drug release behaviors.The injectable hydrogels,as a unique kind of hydrogel,not only possess the advantages of high drug delivery efficiency and drug utilization,but also reduce the systematic side effect with simple injection instead of surgery.In this thesis,in order to improve the effective status of single drugs or monotherapy,a drug delivery system based on injectable hydrogel was designed for dual drug synergistic therapy and combined photothermo/chemo-therapy.First,the pH and redox stimuli-responsive nanohydrogels were synthesized via one-step reflux-precipitation polymerization.Secondly,a dual drug delivery system based on nanogel-incorporated injectable hydrogel(NHG)was designed for sequentially local delivery of doxorubicin(DOX)and combretastatin-A4 phosphate(CA4P)for antiangiogensis and anticancer combination therapy.In vitro studies indicated that the DOX-CA4P@NHG exhibited sequential release behaviors for CA4 P and DOX and high inhibitory activities on the cancer cell proliferation.After a single injection,the DOX-CA4P@NHG displayed superior therapeutic efficacy in xenograft tumor-bearing mice.Immunohistochemistry analyses suggested a synergistic therapeutic effect of DOX-CA4P@NHG system,based on the tumor vascular collapse caused by CA4 P and tumor cell apoptosis resulted by DOX.Finally,the pH stimulated response hydrogel was constructed for chemo-/photothermo-therapy by doping gold nanorods.In vitro studies indicated that the controllable biodegradable injectable hydrogel could obviously inhibit the growth of tumor cells.Thus,the nanogel-incorporated injectable hydrogel system can be employed as a universal platform for tumor therapy.