聚丙烯腈载药纤维的制备及其体外缓释性能评价
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摘要
药物/生物活性物质的载体材料及其先进给药系统已发展成为世界公认的当代生物医学材料重大发展方向和前沿领域之一。随着聚合物科学、医学、药学、纺织科学的不断发展与学科交融,以及新技术的不断涌现,载药纤维作为一种新型生物医药功能材料,其制备开发、应用拓展、相关科学基础与理论都引起了越来越广泛和不断深化的关注。除了基于载药纤维的功能纺织品如保健、理疗、卫生、防护等用途产品外,将载药纤维作为一种新的药物中间剂型,开发新型给药系统的研究目前正在迅猛发展。
本文以聚丙烯腈(PAN)为载体高分子材料,以二甲基乙酰胺为溶剂,分别采用湿法纺丝技术、静电纺丝技术和改性电纺聚丙烯腈超细纤维的方法制备了三种不同类型的PAN载药纤维,对制备的三种载药纤维的结构和性能进行了表征,评价了其体外药物缓释性能。
本文采用湿法纺丝技术制备的聚丙烯腈/羟丙基甲基纤维素载药纤维的拉伸强度达到了纺织加工的要求,说明研究中制备的载药纤维理论上能够进行后续纺织加工制成药用纤维;同时羟丙基甲基纤维素的添加能有效改善药物从聚丙烯腈载药纤维中的释放特征。由于湿法纺丝过程中纤维中的药物会向纺丝浴中扩散渗透,所以采用湿法纺丝制备载药纤维会损失部分药物;制备载药离子交换纤维时,纤维上的药物和溶液中的药物浓度要达到一个动态的吸附平衡,也会损失部分药物;静电纺丝过程不会有药物的损失。
采用紫外分光光度法测定载药纤维中药物的含量。采用红外光谱、扫描电子显微镜、差示扫描量热分析、X-射线晶体衍射等方法对三种载药纤维的性能进行表征。实验结果显示,湿法纺丝和静电纺丝制备的载药纤维中的药物的晶型发生了变化,大部分药物转化为无定形状态;离子交换纤维与药物之间是以离子键的方式相结合;湿法纺丝和静电纺丝制备的载药纤维表面均出现药物颗粒。
使用药物溶出仪,以紫外分光光度法为检测方法,考察了三种载药纤维中药物的体外释药性能及释药机制,作累积释药百分率对时间的药物释放曲线图。体外药物释放试验结果显示所制备的三种载药纤维均不同程度的出现了“暴释”现象,离子交换纤维和静电纺丝制备的超细载药纤维体外释放速度很快,12 h内即释放出可以释放的全部药物;与这两种载药纤维相比湿法纺丝制备的载药纤维在15天左右才可以释放出可以释放的全部药物。
It is based on interdisciplinary approaches, which combine polymer science, pharmaceutics, molecular biology and advanced technologies that new DDS (Drug Delivery System) continuously come into pharmaceutical markets. Not only biotextiles and textiles technologies have some concrete advantages over other materials and the corresponding technologies in pharmaceutical field, but also they can offer new methods and approaches for the preparation of novel DDS. DDS from biotextiles can make patients live easy, improve efficacy and compliance, which are the forever goals of pharmaceutics. Development of novel DDS from biotextiles represents one of the future important orientations for both pharmaceutics and technical textile fields. With polyacrylonitrile (PAN) as matrix and N,N-Dimethylacetamide(DMAc) as the solvent, three different kinds of drug loaded fibers were prepared with wet-spinning process, electrospinning process and modifying electrospinning PAN nanofibers respectively. The properties and the in vitro drug release property of all the drug loaded fibers were investigated.
The drug loaded fibers prepared with wet-spinning method were theoretically strong enough for textile processing, which indicated that the fibers developed with wet-spinning method in this research can be manufactured into drug loaded textiles. And the application of HPMC (hydroxypropyl methylcellulose) can modify the vitro drug release profile of the drug loaded fibers. The actual content of drug in the drug loaded fibers prepared with wet-spinning process was lower than the loading content of it because of the diffusion of drug from fiber into spinning bath.
UV was used to determine the drug loading of the fibers. Three kinds of drug loaded fibers were identified by IR, SEM and DSC test. The results showed that tamoxifen can be bonded with PAN through hydrogen bond in wet-spinning and electrospinning drug loaded fibers, most of the loaded TAM were converted into the amorphous state. And sodium salicylate can be bonded with PAN through electrovalent bond in the drug loaded ion-exchange nanofibers.
In vitro release properties and release mechanism were studied by dissolution apparatus and UV. The curve of the percentage of the cumulative release versus time was made. The results showed that the initial burst effects were manifest in all the drug loaded fibers. The drug loaded fibers prepared with wet-spinning process could release all the tamoxifen they can release during the 15 days dissolution periods, and the application of HPMC in the drug loaded fibers can modify the vitro drug release profile of it. The ultrafine drug loaded fibers prepared with eletrospinning and ion-exchange fibers were able to control the drug release all the drug they can release during the 12 hours dissolution periods.
本文以聚丙烯腈(PAN)为载体高分子材料,以二甲基乙酰胺为溶剂,分别采用湿法纺丝技术、静电纺丝技术和改性电纺聚丙烯腈超细纤维的方法制备了三种不同类型的PAN载药纤维,对制备的三种载药纤维的结构和性能进行了表征,评价了其体外药物缓释性能。
本文采用湿法纺丝技术制备的聚丙烯腈/羟丙基甲基纤维素载药纤维的拉伸强度达到了纺织加工的要求,说明研究中制备的载药纤维理论上能够进行后续纺织加工制成药用纤维;同时羟丙基甲基纤维素的添加能有效改善药物从聚丙烯腈载药纤维中的释放特征。由于湿法纺丝过程中纤维中的药物会向纺丝浴中扩散渗透,所以采用湿法纺丝制备载药纤维会损失部分药物;制备载药离子交换纤维时,纤维上的药物和溶液中的药物浓度要达到一个动态的吸附平衡,也会损失部分药物;静电纺丝过程不会有药物的损失。
采用紫外分光光度法测定载药纤维中药物的含量。采用红外光谱、扫描电子显微镜、差示扫描量热分析、X-射线晶体衍射等方法对三种载药纤维的性能进行表征。实验结果显示,湿法纺丝和静电纺丝制备的载药纤维中的药物的晶型发生了变化,大部分药物转化为无定形状态;离子交换纤维与药物之间是以离子键的方式相结合;湿法纺丝和静电纺丝制备的载药纤维表面均出现药物颗粒。
使用药物溶出仪,以紫外分光光度法为检测方法,考察了三种载药纤维中药物的体外释药性能及释药机制,作累积释药百分率对时间的药物释放曲线图。体外药物释放试验结果显示所制备的三种载药纤维均不同程度的出现了“暴释”现象,离子交换纤维和静电纺丝制备的超细载药纤维体外释放速度很快,12 h内即释放出可以释放的全部药物;与这两种载药纤维相比湿法纺丝制备的载药纤维在15天左右才可以释放出可以释放的全部药物。
It is based on interdisciplinary approaches, which combine polymer science, pharmaceutics, molecular biology and advanced technologies that new DDS (Drug Delivery System) continuously come into pharmaceutical markets. Not only biotextiles and textiles technologies have some concrete advantages over other materials and the corresponding technologies in pharmaceutical field, but also they can offer new methods and approaches for the preparation of novel DDS. DDS from biotextiles can make patients live easy, improve efficacy and compliance, which are the forever goals of pharmaceutics. Development of novel DDS from biotextiles represents one of the future important orientations for both pharmaceutics and technical textile fields. With polyacrylonitrile (PAN) as matrix and N,N-Dimethylacetamide(DMAc) as the solvent, three different kinds of drug loaded fibers were prepared with wet-spinning process, electrospinning process and modifying electrospinning PAN nanofibers respectively. The properties and the in vitro drug release property of all the drug loaded fibers were investigated.
The drug loaded fibers prepared with wet-spinning method were theoretically strong enough for textile processing, which indicated that the fibers developed with wet-spinning method in this research can be manufactured into drug loaded textiles. And the application of HPMC (hydroxypropyl methylcellulose) can modify the vitro drug release profile of the drug loaded fibers. The actual content of drug in the drug loaded fibers prepared with wet-spinning process was lower than the loading content of it because of the diffusion of drug from fiber into spinning bath.
UV was used to determine the drug loading of the fibers. Three kinds of drug loaded fibers were identified by IR, SEM and DSC test. The results showed that tamoxifen can be bonded with PAN through hydrogen bond in wet-spinning and electrospinning drug loaded fibers, most of the loaded TAM were converted into the amorphous state. And sodium salicylate can be bonded with PAN through electrovalent bond in the drug loaded ion-exchange nanofibers.
In vitro release properties and release mechanism were studied by dissolution apparatus and UV. The curve of the percentage of the cumulative release versus time was made. The results showed that the initial burst effects were manifest in all the drug loaded fibers. The drug loaded fibers prepared with wet-spinning process could release all the tamoxifen they can release during the 15 days dissolution periods, and the application of HPMC in the drug loaded fibers can modify the vitro drug release profile of it. The ultrafine drug loaded fibers prepared with eletrospinning and ion-exchange fibers were able to control the drug release all the drug they can release during the 12 hours dissolution periods.
引文
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[1]王金涛,原思国,赵林,王毅.羧酸型离子交换纤维的制备与性能.合成纤维工业,2001,24(6):125-127
[2]符若文,杜秀英,林远声等.强酸型离子交换纤维PVF-g-SO_3H对碱性氨基酸的分离研究.中山大学学报,2001,40(2):45-49.
[3]周林,周绍箕.弱酸性阳离子交换纤维的制备和应用研究.离子交换与吸附,1993,9(6):486-492
[4]李一,张宝文.含氮硫多配位基螯合纤维的合成及其性能研究.离子交换与吸附,1998,14(5):388-396
[5]Ten Breteler M R,Nierstrasz V A and Warmoeskerken M M C G.Textile slow-release systems with medical applications.AUTEX Res J,2002,2(4)175-189.
[6]Moussy Y,Guegan E,Davis T and Koob T.Transport characteristics of a novel local drug delivery system using nordihydroguaiaretic acid(NDGA)-polymerized collagen fibers.Bio Prog,2007,23(4) 990-994.
[7]H(a|¨)nninen K,Kaukonen A M,Murtom(a|¨)ki L and Hirvonen.Mechanistic evaluation of factors affecting compound loading into ion-exchange fibers.Eur J Pharm Sci,2007,31(5) 306-317.
[8]H(a|¨)nninen K,Kaukonen AM,Murtom(a|¨)ki L and Hirvonen.The effect of ion-exchange fiber structure on the binding and release of model salicylates.J Pharm Sci,2005,94(8) 1772-1781.
[9]H(a|¨)nninen K,Murtom(a|¨)ki L,Kaukonen A M and Hirvonen.The effect of valence on the ion-exchange process:theoretical and experimental aspects on compound binding/release.J Pharm Sci,2007,96(1) 117-131.
[10]中华人民共和国卫生部药典委员会.中国药典2000年版.北京:化学工业出版社,2000.
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[14]刘建,闰英桃,刘艳萍,李作思.改性5A分子筛吸附剂从含氟废水中除氟研究.离子交换与吸附,2001,17(2):159-164
[15]张显,魏国,杨敏,高迎新.,错负载型树脂用于含氟废水深度处理的研究.环境污染治理技术与设备,2002,3(5):45-48
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