N-软脂酰基壳聚糖叶酸靶向微泡的体内外特性和靶向效果  

N-palmitoyl chitosan:In vitro and in vivo characterizations and targeting of the folate-targeted ultrasound contrast microbubbles

作　　者：肖云彬[1] 李美瑜[1] 宾建国[1] 廖旺军[1] 刘伊丽[1] 蒋刚彪[2] 宾建平[1] 

机构地区：[1]南方医科大学南方医院心内科,广东广州510515 [2]华南农业大学制药工程系,广东广州510642

出　　处：《中国医学影像技术》2010年第7期1201-1204,共4页Chinese Journal of Medical Imaging Technology

基　　金：国家863计划项目(2006AA02Z478);广东省科技计划项目(2007B030704012)

摘　　要：目的应用N-软脂酰基壳聚糖制备叶酸靶向微泡,评价其基本特征、体外靶向性及体内超声显影效果。方法以高速剪切法制备叶酸靶向微泡和对照微泡,观察叶酸靶向微泡的大小、形态和叶酸分子在微泡的分布及对昆明鼠肾脏的超声显影效果和体外靶向效果,并与对照微泡比较。结果叶酸靶向微泡呈空心球形结构,形态规则,分散均匀,平均粒径(1.32±0.20)μm,浓度(1.93±0.01)×109/ml;鼠肾对比显影明显增强,1min、7min视频强度分别为(30.35±5.01)GU、(17.41±3.15)GU,可视性对比增强持续时间(10.00±3.00)min;与叶酸受体高表达细胞结合数明显大于叶酸受体低表达细胞组和对照微泡组(P<0.01)。结论 N-软脂酰基壳聚糖构建的叶酸靶向微泡可与叶酸受体有效结合,可用其作为分子探针,对叶酸受体高表达的肿瘤进行超声分子成像。Objective To develop a novel folate-targeted ultrasound contrast microbubbles with N-palmitoyl chitosan,and to evaluate its characterizations and specific-site targeting in vitro and in vivo. Methods Folate-targeted microbubbles （MBF） and control microbubbles （MBC） were prepared using high-shear homogenization. The morphology,size and folate molecular fluorescence of microbubbles were characterized. Renal contrast-enhanced imaging with MBF and MBC was performed in 6 mice. MBF and MBC were tested for binding specificity on cells expressing folate receptors and control cells. Results MBF had a good shape,uniform size-distribution and folate-distribution. The mean diameter and concentration was （1.32±0.20）μm and （1.93±0.01）×10^9/ml. Significant enhancement on kidneys was noted in contrast ultrasound imaging with MBF. The video intensity of renal tissue was （30.35±5.01）GU and （17.41±3.15）GU at 1 and 7 min after bolus injection,respectively. The duration time of visual enhancement was （10.00±3.00）min. The binding number of MBF in group of the over-expression folate receptors cells was higher than those of MBF in group of the low-expression folate receptors cells and MBC groups （P〈0.01）. Conclusion The novel ultrasound contrast microbubbles with N-palmitoyl chitosan can specifically and effectively bind to folate receptors. It may be used to evaluate the over-expression folate receptors＇s tumors or other pathological changes noninvasively with ultrasound imaging.

关 键 词：壳聚糖 叶酸 造影剂 微泡 

分 类 号：R981.2[医药卫生—药品] R445.1[医药卫生—药学]