Journal
BIOMATERIALS
Volume 30, Issue 5, Pages 959-967Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.10.031
Keywords
Antisense quantification; Antisense delivery; Erythrocyte ghost; Opsonization; Liver targeting
Funding
- Ministry of Education, Science and Technology [F104AA010003-08A0101-00310]
- Korea Science and Engineering Foundation (KOSEF) [R01-2005-000-10292-0]
- National Research Foundation of Korea [과C6A2102, 핵C6B3407, 2006-0052142, R01-2005-000-10292-0, 2006-08305] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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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