Opsonized erythrocyte ghosts for liver-targeted delivery of antisense oligodeoxynucleotides

详细信息    查看全文

• 作者：Sang-Hee Kim ; Eun-Joong Kim ; Joon-Hyuk Hou ; Jung-Mogg Kim ; Han-Gon Choi ; Chang-Koo Shim ; Yu-Kyoung Oh
• 关键词：Antisense quantification ; Antisense delivery ; Erythrocyte ghost ; Opsonization ; Liver targeting
• 刊名：Biomaterials
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：30
• 期：5
• 页码：959-967
• 全文大小：734 K

文摘

The use of antisense oligodeoxynucleotides (AS-ODNs) in therapeutic applications requires the development of appropriate analysis and delivery systems. Here, we report a quantitation method and a carrier-mediated AS-ODN delivery system. AS-ODN levels were quantitated using an enzyme-linked immunosorbent assay (ELISA) in which biotinylated AS-ODNs bound to streptavidin-coated plates were detected by binding of a complementary, dinitrophenol-labeled detector ODN. The ELISA-based assay could detect AS-ODNs at the femtomole level. AS-ODN delivery systems based on opsinized erythrocyte ghosts (EGs) were developed using various combinations of hypotonic solution and resealing buffer to optimize AS-ODN encapsulation efficiencies. AS-ODN and polyethyleneimine (PEI) complex formation did not affect encapsulation into EGs. The ELISA-based assay showed that the pharmacokinetics of AS-ODNs differed significantly among the various delivery methods. Opsonized EG-encapsulated AS-ODNs exhibited a mean residence time (MRT) significantly shorter than AS-ODN encapsulated in EGs. The biodistribution of EG-loaded AS-ODNs depended on opsonization, with opsonized EG carriers producing 4.5-fold higher levels of AS-ODN in the liver compared with unopsonized EGs. These results indicate that opsonized EGs can be used for liver-targeted delivery of AS-ODN and suggest that an ELISA-based method may be useful for studying the in vivo fate of AS-ODNs.