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

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Chinese Medical Journal 2018年第6期131卷 696-703页

作者： Tao Wang Hao Zou Yun-Xia Liu Xiao-Wen Zhang Department of Hepatopancreatobiliary Surgery The Second Affiliated Hospital of Kunming Medical University Kunming Yunnan 650101 China Graduate Division Kunming Medical University Kunming Yunnan 650500 China Basic Medical Division Experiment Teaching Center Kunming Medical University Kunming Yunnan 650500 China

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 ）, whereas no statistically significant difference w

关键词： Biliary Stricture Chitosan Paclitaxel ProliferativeCholangitis slow-releasing

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A Novel Design Strategy for Temperature-Responsive IPN Hydrogels Based on a Copolymer of Acrylamide and N-(1,1-Dimethyl-3-Oxobutyl)-Acrylamide

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Advances in Chemical Engineering and Science 2018年第4期8卷 255-270页

作者： Yu Wang Huifang Xia Jun Zhao Xiuqin Cai Shengke Chen Bengxiu Li School of Chemistry and Materials Sciences Guizhou Education University Guiyang China Anshun Engineering Research Centre of Concrete Admixture Anshun China School of Chemistry and Materials Science Weinan Normal University Weinan China GuizhouTiejinahengfa New Material Technology Co. Ltd. Anshun China

A methology is described for the synthesis of novel temperature-responsive interpenetrating polymer network (IPN) hydrogels with poly(2-acrylamido- 2-methylpropane sulfonic acid) (PAMPS) as a tightly crosslinked 1st network, temperature-responsive poly(acrylamide-co-N-(1,1-dimethyl-3-oxobutyl)- acrylamide) (P(AM-co-DAAM)) with low cost as a lossely crosslinked 2nd network. The structure and morphology of the IPN hydrogels were characterized by FTIR, TGA and SEM, and the results indicated that PAMPS network introduced P(AM-co-DAAM) hydrogels have large, thermally stable and interconnected porous network. The properties of the IPN hydrogels, which include: swelling capacity, equilibrium swelling/deswelling ratio, temperature- responsive behavior, and the dwelling kinetics as specific temperature, were investigated carefully. Results showed that the obtained IPN hydrogels displayed a controllable equilibrium swelling/deswelling behavior and possessed remarkable thermosensitivity. In addition, the results also indicate that the incorporation of the hydrophobic groups DAAM has a big effect on the LCST of the IPN hydrogels. Consequently, these novel temperature-responsive IPN hydrogels with low cost and slow-releasing performance would be promising for potential applications, such as environmental catalysis, water treatment, and agriculture.

关键词： Temperature-Responsive Hydrogel Interpenetrating Polymer Network Equi-librium Swelling Ratio slow-releasing Performance

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