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 n...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.展开更多
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 loca...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 展开更多
克服水溶性药物的突释现象,可减少给药次数,提高疗效.本研究以卡托普利为模型药物,壳聚糖为载体,采用耦合的方法,设计合成了壳聚糖-卡托普利和壳聚糖-赖氨酰-卡托普利两种新的键连型壳聚糖基载药体系,产物结构经IR、1 H NMR和MS表征;并...克服水溶性药物的突释现象,可减少给药次数,提高疗效.本研究以卡托普利为模型药物,壳聚糖为载体,采用耦合的方法,设计合成了壳聚糖-卡托普利和壳聚糖-赖氨酰-卡托普利两种新的键连型壳聚糖基载药体系,产物结构经IR、1 H NMR和MS表征;并测试了两种化合物在PBS缓冲溶液(pH=7.4)和HCl-KCl缓冲溶液(pH=1.2)中72h的累积释药率:壳聚糖-卡托普利的累积释药率分别为59.2%和78.4%,壳聚糖-赖氨酰-卡托普利的累积释药率分别为55.2%和76.4%.结果表明,两种键连型载药体系均消除了突释现象,具有很好的缓释效果,这将有望成为水溶性药物的理想载药体系.展开更多
文摘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.
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）.
文摘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
文摘克服水溶性药物的突释现象,可减少给药次数,提高疗效.本研究以卡托普利为模型药物,壳聚糖为载体,采用耦合的方法,设计合成了壳聚糖-卡托普利和壳聚糖-赖氨酰-卡托普利两种新的键连型壳聚糖基载药体系,产物结构经IR、1 H NMR和MS表征;并测试了两种化合物在PBS缓冲溶液(pH=7.4)和HCl-KCl缓冲溶液(pH=1.2)中72h的累积释药率:壳聚糖-卡托普利的累积释药率分别为59.2%和78.4%,壳聚糖-赖氨酰-卡托普利的累积释药率分别为55.2%和76.4%.结果表明,两种键连型载药体系均消除了突释现象,具有很好的缓释效果,这将有望成为水溶性药物的理想载药体系.
