载纳米羟基磷灰石放线菌素D缓释微球骨水泥的制备  

Preparation and characterization of a type of cement containing actinomycin D microspheres

作　　者：薛忠林 靳安民 张辉 于博 闵少雄 敖俊 

机构地区：[1]广东省广州市珠江医院骨科,广州510280

出　　处：《中国新药杂志》2009年第8期749-754,共6页Chinese Journal of New Drugs

基　　金：广东省科技计划项目课题(20070328017)

摘　　要：目的：研制一种含药物微球的可塑形骨水泥并了解其载药和释药特征。方法：载药骨水泥的制备分4步进行：首先制备出载药的纳米羟基磷灰石（nano-HA）,然后将其与药物放线菌素D（Act-D）混合,以此混合物为基础制备出纳米羟基磷灰石-聚羟基丁酸戊酯/聚乙二醇-放线菌素D（nano-HA-PHBV/PEG-Act-D）缓释微球,最后将其与胶原等混合制成可塑形骨水泥。测定纳米羟基磷灰石、载药微球和骨水泥的表征、载药量及体外药物释放。结果：X射线衍射法对nano-HA进行晶粒度分析,图形显示为HA特征性峰值,其中未出现其他杂质干扰峰。在透射电镜下可见nano-HA为纳米相晶体颗粒,平均为20-60 nm,nano-HA-Act-D大小在100-300 nm左右,nano-HA-PHBV/PEG-Act-D微球透射结构为PHBV/PEG膜包裹nano-HA-Act-D形成微球。扫描电镜观察：制备的微球呈白色,形态大小均匀规整,微球表面形态一致,表面为多孔呈皱缩结构。药物Act-D均能从药物微球和载药骨水泥中向PBS液中缓慢扩散,具有明显缓释作用。结论：载nano-HA-PHBV/PEG-Act-D微球的可塑形骨水泥制作工艺简单,对药物有较强承载和缓释能力,可作为局部肿瘤切除术后填充骨缺损并防止局部复发的良好载药材料。Objective： To prepare and characterize a type of cement containing actinomycin D （Act-D） microspheres which were composed of nano-hydroxypatite （nano-HA） and poly hydroxybutyrate-co-hydroxyvalerate/polyethylene glycol （PHBV/PEG）. Methods： The nano-HA was prepared as the core carrier to load Act-D, and the nano-HA-PHBV/PEG-Act-D microspheres were then fabricated by mixing the nano-HA-Act-D and the compounds of PHBV/PEG. The microspheres were incorporated into fibrin gelatin （FG） so that the final product of a plastic implant was made. The characterization and in vitro drug release properties of the microspheres and cement were investigated respectively. Results： The X-ray diffraction （XRD） pattern revealed the characteristic peaks of nano-HA and no secondary interfere peaks. Transmission electron microscope （TEM） image showed that the size of nod-like HA nanoparticles was about 20 - 60 nm in length. The drug molecules were adsorbed on the surface of HA nanoparticles, which tended to sphere-like form in the organic dispersion medium and congregated together. TEM images also indicated that the nano-HA-PHBV/PEG-Act-D microspheres had hybrid structure with two phase： PHBV/PEG made of the polymer matrices and nano-HA particles that distributed in the matrices formed separated phase. Act-D could be slowly delivered from the microspheres and the samples of cement, and an even release maintained within 8 weeks. Conclusion： It is simple to make the nano-HA-PHBV/PEG-Act-D microspheres and the plastic plants. This type of cement should have a widespread promise to fi｜l the defects of limbs caused by operation, and prevent the postoperative relapse of certain tumor.

关 键 词：纳米羟基磷灰石 放线菌素D 微球 骨水泥 

分 类 号：R943.41[医药卫生—药剂学] R979.14[医药卫生—药学]