Paclitaxel-modified Chitosan Hydrogel Membrane Preparation,Properties and Inhibit Rabbit Bile Duct Scar

Author:Wang Tao

Supervisor:zhang xiao wen


Degree Year:2018





Objective:Refers to a benign biliary stricture caused by excessive tissue repair after injury of bile duct of the bile ducts cavity cicatricial stenosis,its specific mechanism is still not fully understood.Clinical treatment of BBS is numerous,surgery is still the gold standard in the clinical treatment of benign biliary stricture,but biliary postoperative may still be narrow,repair caused by obstructive jaundice,cholestasis complications of cirrhosis and is difficult to correct,will eventually threaten patient’s life.Currently found that not only can be used in the clinical treatment of a wide variety of tumor,taxol in stent in the treatment of coronary artery stenosis,scleroderma,and prevention of scar formation after glaucoma surgery with curative effect affirmation.But due to the poor water soluble taxol and cosolvent side effects such as faults,limiting the clinical popularization and application of paclitaxel.Therefore the development of new drug delivery system and improve the methods of drug delivery,in order to improve the efficiency,avoid adverse reaction,has become a hot research topic in the field of drug.Chitosan and its derivatives have good bioconpatibility,degradability,non-toxic,its metabolic product is harmless to human body and film-forming properties,such as biological properties,has been in chemical,material,medicine and other fields have a wide range of research and application.This experiment by copolymerization modified chitosan derivatives drug taxol,the preparation of paclitaxel-N-succinyl hydroxyethyl chitosan hydrogel membrane,its physical and chemical and biological properties,to evaluate the feasibility of it as surgical implants.To further study the effect of slow release membrane bile duct stricture formation to animals,in order to provide prevention and control of benign bile duct stricture ideal slow-release material and new measures.Method:1,The preparation and purification of hydroxyethyl chitosan,the degree of its,the molecular weight,elements and hydroxyethyl combined rate structure parameters,such as testing,characterization and application of the infrared,nuclear magnetic structure,and testing the moisture,ash content,PH,viscosity,conductivity,protein content,heavy metal content such as the physical and chemical properties.2,N-succinyl hydroxyethyl chitosan preparation and purification,the structure parameters-amber acylation degree testing,infrared,imaging the structure were characterized at the same time.3,The preparation of different crosslinking ratio of paclitaxel-N-succinyl hydroxyethyl chitosan hydrogel membrane,infrared,nuclear magnetic,characterization of its structure,the calculation theory of drug loadings,and slow release membrane and carrier of water absorption and swelling ratio detection,through the cell toxicity,skin irritation,biodegradability and biocompatibility experiment system evaluate the safety of sustained-release film and substrate.4,The application of high performance liquid chromatography(HPLC)different crosslinking ratio of controlled-release membranes in vitro sustained release performance.5,Making animal model of rabbit benign bile duct stricture with sustained release membrane intervention,the model line detecting liver function,gross observation,bile duct tissues HE and Masson staining and immunohistochemical detection of α-SMA,Ⅰ,Ⅲ expression of collagen type and rating,comprehensive evaluation of its inhibitory effect on rabbit benign biliary stricture formation.Results:1,Hydroxyethyl chitosan preparation by the quality of the physical and chemical indexes meet the requirements,will be success.2,Paclitaxel,side to the N-succinyl hydroxyethyl chitosan,and making the proportion of different crosslinking of slow-releasing membranes,its theoretical drug loadings is 80 μg/cm2.3,Sustained release carrier film and has no obvious cell toxicity,no skin irritation and has good degradability and intermiscibility of organization,the safety of diaphragm is implanted.4,Sustained release membrane in vitro in PBS solution,with the release of a certain performance,and with the increase of crosslinking degree,drug release rate slowed.5,Successfully make the rabbit model of benign biliary stricture,sustained release membrane implant after the intervention,not cause liver function change and bile duct expansion,histopathologic changes than the control group obviously,α-SMA,collagen and other indicators are lower,has the inhibitory effect of benign biliary stricture formation.Conclusion:The successful preparation of chemical combination of PTX-Suc-HEC TS piece,its chemical structure by ir and nuclear magnetic characterization.Load carrier slices and excellent physical and chemical properties,biological properties,instructions will be its implanted in the body has the feasibility and safety.Sustained release membrane of different crosslinking degree,there is a difference in vitro release properties.Sustained release membrane has a certain inhibitory effect of rabbit benign biliary stricture.