Feasibility and efficacy evaluation of metallic biliary stents eluting gemcitabine and cisplatin for extrahepatic cholangiocarcinoma  

作　　者：Jing-Bo Xiao Jun-Yong Weng Yang-Yang Hu Gui-Long Deng Xin-Jian Wan 

机构地区：[1]Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Diseases,Shanghai General Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 201620,China [2]Hospitalist and Internal Medicine Inpatient Department,Shanghai Jiahui International Hospital,Shanghai 200233,China [3]Department of General Surgery,Shanghai General Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 201620,China [4]Department of Gastroenterology,Shanghai Jiao Tong University Affiliated Sixth People's Hospital,Shanghai 200233,China

出　　处：《World Journal of Gastroenterology》2020年第31期4589-4606,共18页世界胃肠病学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China,No.81870452 and No.81470904;Science and Technology Development Funds of Shanghai of China,No.16411952400.

摘　　要：BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma(ECC).However,current biliary stents that are widely used in clinical practice showed no antitumor effect.Drug-eluting stents(DESs)may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis.AIM To develop novel DESs coated with gemcitabine(GEM)and cisplatin(CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity.METHODS Stents coated with different drug-eluting components were prepared by the mixed electrospinning method,with poly-L-lactide-caprolactone(PLCL)as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents.Four different DESs were manufactured with four drug-loading ratios(5%,10%,15%,and 20%),including bare-loaded(PLCL-0),single-drug-loaded(PLCL-GEM and PLCL-CIS),and dual-drug-loaded(PLCL-GC)stents.The drug release property,antitumor activity,and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC.RESULTS The in vitro drug release study showed the stable,continuous release of both GEM and CIS,which was sustained for over 30 d without an obvious initial burst,and a higher drug-loaded content induced a lower release rate.The drug-loading ratio of 10%was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity.All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo;in addition,the dual-loaded nanofilm(PLCL-GC)had a significantly better effect than the single-drug-loaded nanofilms(P<0.05).No significant differences in the serological analysis(P>0.05)or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract.CONCLUSION This novel PLCL-GEM and C

关 键 词：Extrahepatic cholangiocarcinoma Drug-eluting stent Local chemotherapy GEMCITABINE CISPLATIN Biliary obstruction 

分 类 号：R735.8[医药卫生—肿瘤]