阿霉素载药栓塞微球的制备和性能表征

Preparation and Characterization of Doxorubicin Loaded Microspheres for Embolization

目的:研究离子交换型阿霉素载药透明质酸栓塞微球(DHAMs)的制备方法及性能表征。方法:采用油包水(W/O)乳化交联法,以改性透明质酸(HA)为载药基质,通过离子交换原理制备载阿霉素的透明质酸栓塞微球。采用光学显微镜、扫描电子显微镜观察表面形态,考察粒径和溶胀率;采用恒温摇床模拟体内环境初步测定透明质酸微球降解率;采用紫外分光光度法测定DHAMs载药量、包封率和体外释放率;采用傅里叶变换红外光谱(FT-IR)和粉末X射线衍射法(PXRD)对DHAMs进行表征。结果:透明质酸微球形态圆整、表面光滑,平均粒径为(111.83±12.21)μm,溶胀率为201.81%;微球56 d体外降解率为34.31%;微球载药量和包封率分别为(22.09%±0.05%)和(99.41%±0.21%),且72 h累计释放量可达50%;FT-IR和PXRD分析显示,阿霉素在微球中以无定形形式存在。结论:阿霉素透明质酸微球有较好的载药性能,理化性能良好,具有动脉化疗栓塞的应用前景。

Objective:To prepare ion exchange doxorubicin-loaded hyaluronic acid microspheres and characterize their properties.Methods:Modified hyaluronic acid was used as the drug carrier matrix to prepare microspheres using a water-in-oil(W/O)emulsion crosslinking method,then doxorubicin hydrochloride was loaded by ion exchange mechanism to prepare drug-loaded microspheres.The surface morphology of microspheres was observed by optical microscopy and scanning electron microscopy,and the particle size and swelling ratio of microspheres was measured.The degradation rate was determined by simulating in vivo environment with a shaking incubator.The drug loading,encapsulation efficiency,and in vitro release rate were determined using UV spectrophotometry.The doxorubicin hydrochloride loaded microspheres were characterized by Fourier transform infrared spectroscopy(FT-IR)and powder X-ray scattering techniques(PXRD).Results:The microspheres were spherical with smooth surfaces in morphology,and had an average particle size of(111.83±12.21)μm and a swelling ratio of 201.81%.The in vitro degradation rate of the microspheres at 56 days was 34.31%.The drug loading and encapsulation efficiency were(22.09%±0.05%)and(99.41%±0.21%),respectively,with a cumulative release of up to 50%after 72 h.FT-IR and PXRD analysis showed that doxorubicin hydrochloride existed in an amorphous form.Conclusion:The microspheres had good performance of doxorubicin loading and physical and chemical properties,which could be a potential embolic agent for transcatheter arterial chemoembolization.