Optimization And Pharmacodynamic Evaluation Of The Anti Osteosarcoma Drug Delivery System Of The Multiple Drug-Loaded Phosphene Thermosensitive Hydrogel

Object: In order to obtain a stable and controllable multiple drug-loaded thermosensitive hydrogel anti osteosarcoma delivery system,chitosan hydroxyapatite black phosphorus nanosheets composite hydrogel was prepared by using chitosan,hydroxyapatite and black phosphorus nanosheets to carry doxorubicin and cisplatin chemotherapy drugs,forming a new drug dosage form of local injection of multiple drug-loaded chemotherapy radiotherapy promoting bone regeneration and repair.A series of characterization,stability inspections,photothermal effect evaluation,in vitro drug release,in vitro cytological level and in vivo animal level inspections were carried out on the prepared multiple drug-loaded phosphene thermosensitive hydrogel to comprehensively evaluate the synergistic treatment effect on osteosarcoma.Methods:(1)Chitosan hydroxyapatite black phosphorus nanosheets composite hydrogel was prepared by using chitosan,hydroxyapatite and black phosphorus nanosheets,and the ratio between chitosan and hydroxyapatite in the prescription was optimized by taking gel temperature and gel time as indicators;(2)It was characterized by transmission electron microscope,scanning electron microscope,UV-visible spectrum and rheological parameters;(3)Its stability was preliminarily evaluated by appearance,p H change value and UV-visible spectrum;(4)To investigate its photothermal effect,and further evaluate the in vitro drug release of the multi drug loaded thermosensitive hydrogel of phosphene in different phases(liquid,solid),different p H(health tissue p H=7.2,tumor tissue p H=5.0),different time(fresh configuration 0 d,standing for 7 d),single drug and multi drug;(5)In vitro cytology was used to investigate its role in killing tumor cells,affecting cell apoptosis cycle,and in situ biomineralization of cell microenvironment;(6)In vivo zoology evaluation of its inhibitory effect on tumor growth and toxic and side effects on major tissues and organs.Results:(1)The preparation process was optimized,and the multiple drug-loaded phosphene thermosensitive hydrogel could be stably prepared for anti osteosarcoma.The prescription conditions were chitosan 4%-6%,hydroxyapatite: chitosan=1:10-20;(2)It has good stability and biosafety,and excellent photothermal effect;(3)It can release stably under various release conditions simulated in vitro;(4)Animal experiments show that it has good anti-tumor effect in vivo and low tissue toxicity.Conclusion: The optimized preparation process can stably prepare the multiple drug-loaded thermosensitive hydrogel anti osteosarcoma drug delivery system.The preparation method is simple,and it has obvious nearinfrared light release characteristics and good photothermal performance.It can meet the requirements of tumor treatment by using photothermal/chemotherapy coordination,and has broad application prospects in two-dimensional nanomaterial drug delivery systems.