Opsonized erythrocyte ghosts for liver-targeted delivery of antisense oligodeoxynucleotides
- Authors
- Kim, Sang-Hee; Kim, Eun-Joong; Hou, Joon-Hyuk; Kim, Jung-Mogg; Choi, Han-Gon; Shim, Chang-Koo; Oh, Yu-Kyoung
- Issue Date
- 2월-2009
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Antisense quantification; Antisense delivery; Erythrocyte ghost; Opsonization; Liver targeting
- Citation
- BIOMATERIALS, v.30, no.5, pp.959 - 967
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOMATERIALS
- Volume
- 30
- Number
- 5
- Start Page
- 959
- End Page
- 967
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/120676
- DOI
- 10.1016/j.biomaterials.2008.10.031
- ISSN
- 0142-9612
- Abstract
- 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 polyethylene imine (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. (C) 2008 Elsevier Ltd. All rights reserved.
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