Effects of Paclitaxel-conjugated N-SuccinyI-Hydroxyethyl Chitosan Film for Proliferative Cholangitis in Rabbit Biliary Stricture Model  

作　　者：Tao Wang Hao Zou Yun-Xia Liu Xiao-Wen Zhang 

机构地区：[1]Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China [2]Graduate Division, Kunming Medical University, Kunming, Yunnan 650500, China [3]Basic Medical Division, Experiment Teaching Center, Kunming Medical University, Kunming, Yunnan 650500, China

出　　处：《Chinese Medical Journal》2018年第6期696-703,共8页中华医学杂志（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China （No. 81260084） and the Applied Basic Research Project in Yunnan Province （No. 2011 fb162）.

摘　　要：Background： Paclitaxel （PTX） could inhibit the growth of fibroblasts, which occurs in proliferative cholangitis and leads to biliary stricture. However, its use has been limited due to poor bioavailability and local administration for short time. This study designed and synthesized a new PTX-conjugated chitosan film （N-succinyl-hydroxyethyl chitosan containing PTX [PTX-SHEC]） and evaluated its safety and efficiency using in vivo and in vitro experiments. Methods： The SHEC conjugated with PTX was confirmed by nuclear magnetic resonance （NMR） and Fourier-transform infrared spectroscopy （FT-IR） measurements. Drug releases in vitro and in vivo were determined using high-performance liquid chromatography. Cell viability in vitro was measured using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide. Rabbit biliary stricture model was constructed. All rabbits randomly divided into five groups （n = 8 in each group）： the sham-operated rabbits were used as control （Group A）, Groups B received laparotomies and suture, Group C received laparotomies and covered SHEC suture without the PTX coating, Group D received laparotomies and covered PTX-SHEC suture, and Group E received laparotomies and 1000 μmol/L PTX administration. Liver function tests and residual dosage of PTX from each group were measured by enzyme-linked immunosorbent assay. Histological data and a-smooth muscle actin （SMA） immunohistochemical staining of common bile duct were examined. Results： NMR and FT-1R indicated that PTX was successfully introduced, based on the appearance of signals at 7.41-7.99 ppm, 1.50 ppm, and 1.03 ppm, due to the presence of aromatic protons, methylene protons, and methyl protons of PTX, respectively. No bile leak was observed. The PTX-conjugated film could slowly release PTX for 4 weeks （8.89 ± 0.03/ag at day 30）. The in vitro cell viability test revealed significantly different levels of toxicity between films with and without PTX （[ 11.7± 4.0% vs. 68. l±6.0%, P 〈 0.001 Background： Paclitaxel （PTX） could inhibit the growth of fibroblasts, which occurs in proliferative cholangitis and leads to biliary stricture. However, its use has been limited due to poor bioavailability and local administration for short time. This study designed and synthesized a new PTX-conjugated chitosan film （N-succinyl-hydroxyethyl chitosan containing PTX [PTX-SHEC]） and evaluated its safety and efficiency using in vivo and in vitro experiments. Methods： The SHEC conjugated with PTX was confirmed by nuclear magnetic resonance （NMR） and Fourier-transform infrared spectroscopy （FT-IR） measurements. Drug releases in vitro and in vivo were determined using high-performance liquid chromatography. Cell viability in vitro was measured using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide. Rabbit biliary stricture model was constructed. All rabbits randomly divided into five groups （n = 8 in each group）： the sham-operated rabbits were used as control （Group A）, Groups B received laparotomies and suture, Group C received laparotomies and covered SHEC suture without the PTX coating, Group D received laparotomies and covered PTX-SHEC suture, and Group E received laparotomies and 1000 μmol/L PTX administration. Liver function tests and residual dosage of PTX from each group were measured by enzyme-linked immunosorbent assay. Histological data and a-smooth muscle actin （SMA） immunohistochemical staining of common bile duct were examined. Results： NMR and FT-1R indicated that PTX was successfully introduced, based on the appearance of signals at 7.41-7.99 ppm, 1.50 ppm, and 1.03 ppm, due to the presence of aromatic protons, methylene protons, and methyl protons of PTX, respectively. No bile leak was observed. The PTX-conjugated film could slowly release PTX for 4 weeks （8.89 ± 0.03/ag at day 30）. The in vitro cell viability test revealed significantly different levels of toxicity between films with and without PTX （[ 11.7± 4.0% vs. 68. l±6.0%, P 〈 0.001

关 键 词：Biliary Stricture CHITOSAN PACLITAXEL ProliferativeCholangitis Slow-Releasing 

分 类 号：S829.1[农业科学—畜牧学] TQ464.5[农业科学—畜牧兽医]