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Opsonized erythrocyte ghosts for liver-targeted delivery of antisense oligodeoxynucleotides

Paper ID Volume ID Publish Year Pages File Format Full-Text
9441 629 2009 9 PDF Available
Title
Opsonized erythrocyte ghosts for liver-targeted delivery of antisense oligodeoxynucleotides
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 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.

Keywords
Antisense quantification; Antisense delivery; Erythrocyte ghost; Opsonization; Liver targeting
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Opsonized erythrocyte ghosts for liver-targeted delivery of antisense oligodeoxynucleotides
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 5, February 2009, Pages 959–967
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us