Preparation,characterization And Animal Experiment Study Of Alginate Drug Carrier

Due to the systemic chemotherapy and radiotherapy have serious side effects on patients,local cancer therapy plays an important role in cancer treatment.Local chemotherapy has been widely used in clinical.However,there are still some problems.Developing diverse local drug elution devices can help solving these problems and provide more options for patients.In this study,alginate was used as a matrix material to prepare local drug eluting polymer implants.The drug loading mechanism and application in animal models were explored.The main research work are as follows:In Chapter 2,the preparation of alginate membranes by spin-coating,freeze-drying and electrospinning methods is used as a drug carrier in local cancer therapy.The surface morphology,specific surface area,mechanical properties of the sample,as well as the adsorption and in vitro release performance are tested.The results show that the spin-coated film has the greatest tensile strength,the spun film has the largest specific surface area and THP encapsulation rate,and the freeze-dried membranes has better stability and better drug release performance.THP and alginate can be quickly combined through ion exchange reaction,and the drug can be loaded within a few hours before surgery by immersion.All the three kinds of THP-loaded alginate membranes have better drug release properties.Chapter 3,electrospinning was used to prepare alginate covered airway stents and characterize their performance.Since the alginate electrospinning fiber prepared in Chapter 2 still has some defects,the spinning process parameters are optimized first,and then the optimized process conditions are used to prepare the alginate-coated airway stent.The final spinning conditions are: solution concentration4%w/v,SA/PEO=9:1,voltage 24 k V,flow rate 1m L/h.Finally,a fiber membrane with a diameter of 146±32nm and no beads is obtained.The mechanical properties,porosity,and water permeability of the fiber membrane can meet the actual application requirements.The drug loading and soaking can be obtained by soaking in THP solutions of different concentrations.In terms of time,the required dose of the experimental rabbit can be reached within 3 hours.In Chapter 4,the safety and effectiveness of the prepared drug-loaded stent-covered tracheal stent was verified by placing the prepared alginate stent-covered stent into the trachea of experimental rabbits.The experimental rabbits survived well after the stent was implanted.The proliferation thickness of tracheal granulation tissue in the experimental group with the drug-loaded stent was significantly lower than the control group,which verified the effectiveness of the prepared local chemotherapy stent.At 2 and 4 weeks after stent placement,the histological analysis of the experimental rabbit trachea showed that the prepared local chemotherapy stent helped to reduce the restenosis rate after stent placement.The liver and kidney function indexes of the experimental rabbits were all normal within 4weeks after stent placement.And the heart,liver,spleen,lung,kidney and other organs have no abnormalities,which verifies the safety of local chemotherapy stents and is expected to be used in clinical practice.