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KMID : 0617320030120010171
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Journal of Pharmacetical Sceiences Ewha Womans University
2003 Volume.12 No. 1 p.171 ~ p.180
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Surface-modified poly(lactide-··-glycolide) nanospheres for targeted bone imaging with enhanced labeling and delivery of radioisotope
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Park, Yoon Jeong
Nah, Sook Hee/Lee, Jue Yeon/Jeong, Jae Min/Chung, Jun Key/Lee, Myung Chul/Yang, Victor C.
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Abstract
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Surface-modified nanospheres can be utilized for targeting drugs and diagnostic agents to the bone and bone marrow while extending their circulation time in the blood stream. The surface modification of poly(lactide-co-glvcolide)(PLGA) nanospheres by radioisotope carrying poly(ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) triblock copolymers (Poloxamer 407) has been assessed by in vitro characterization and in vim biodistribution studies after intravenous administration of the nanospheres to the mouse. A hydroxyphenylpropionic acid, a ligand for ^(125)I and ^(131)I labeling, was conjugated to the hydroxyl group of the Poloxamer 407 by using dicyclohexyl carbodiimide. The ligand-conjugated Poloxamer 407 was adsorbed onto the surface of PLGA nanospheres. Surface coating was confirmed by measuring both size distribution and the surface charge of the nanospheres. Besides, ^(125)I-labeling efficiency, radiolabeling stability, whole body imaging, and biodistribution of the radioisotope-labeled nanosphercs were examined. Ligand-labeled, surface-modified PLCA nanospheres were in 100-nm size ranges, which may be adequate for long-circulation and further bone imaging. ^(125)I-labeling efficiency was >90% and was more stable at human serum for 24 h. A noticeable decrease in liver or spleen uptake was obtained by the surface-modified nanospheres, ^(125)I-labeled nanospheres showed higher blood maintenance and bone uptake compared with stannous colloid with the same size distribution. Therefore, a fully biodegradable, radioisotope-carrying, surface-modified nanosphere system has been developed as a promising tool for targeting bone and bone marrows.
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