Choi Jin Woo, Park Ju-Hwan, Baek Song Yi, Kim Dae-Duk, Kim Hyo-Cheol, Cho Hyun-Jong
Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Colloids Surf B Biointerfaces. 2015 Aug 1;132:305-12. doi: 10.1016/j.colsurfb.2015.05.037. Epub 2015 May 27.
Doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were fabricated using the solid-in-oil-in-water (S/O/W) emulsification method for transarterial chemoembolization (TACE) of a liver tumor. DOX-loaded PLGA MSs with a mean diameter of 26 μm and a spherical shape were prepared. The biodegradation of PLGA MSs was observed in serum using a scanning electron microscope (SEM). Drug release from the PLGA MSs was accelerated at an acidic pH (pH 5.5) compared to a normal physiological pH (pH 7.4). According to the results of a pharmacokinetic study in rats, the area under the curve (AUC) value of a drug, which indicates the systemic exposure extent of the drug, of the PLGA MSs group was 29.9% of that of a hepatic arterial injection (HAI) group. The DOX concentration ratio for liver tumors compared to normal livers was significantly higher in the PLGA MSs group than that of the HAI group (p<0.05). After the TACE procedure was performed with DOX-PLGA MSs in a rat hepatoma model, the mean size increment of tumor in DOX-PLGA MSs group was found to be lower than that of the HAI group, and the viable portion of the DOX-PLGA MSs group was less than the other groups (p<0.05). All these findings suggested that the developed DOX-loaded PLGA MSs fabricated with the S/O/W method can be used as a promising drug delivery system in TACE for liver tumors.
采用水包油包固（S/O/W）乳化法制备了载有多柔比星（DOX）的聚乳酸-羟基乙酸共聚物（PLGA）微球（MSs），用于肝肿瘤的经动脉化疗栓塞（TACE）。制备了平均直径为26μm且呈球形的载DOX的PLGA MSs。使用扫描电子显微镜（SEM）观察了PLGA MSs在血清中的生物降解情况。与正常生理pH（pH 7.4）相比，PLGA MSs在酸性pH（pH 5.5）下的药物释放加速。根据大鼠药代动力学研究结果，PLGA MSs组药物的曲线下面积（AUC）值（表明药物的全身暴露程度）为肝动脉注射（HAI）组的29.9%。PLGA MSs组肝肿瘤与正常肝脏的DOX浓度比显著高于HAI组（p<0.05）。在大鼠肝癌模型中用DOX-PLGA MSs进行TACE手术后，发现DOX-PLGA MSs组肿瘤的平均大小增量低于HAI组，且DOX-PLGA MSs组的存活部分少于其他组（p<0.05）。所有这些发现表明，采用S/O/W方法制备的新型载DOX的PLGA MSs可作为肝肿瘤TACE中有前景的药物递送系统。
