Akademik Veri Yönetim Sistemi
OLIGONUCLEOTIDES, cilt.20, ss.147-153, 2010 (SCI-Expanded)
Skin delivery of antisense oligonucleotides (AsODNs) has exciting potential in the treatment of skin diseases. However, the therapeutic applications of oligonucleotide-based therapies are limited by the instability of these molecules toward nucleases, short half-life in vivo, and insufficient cellular uptake. The purpose of this study was to investigate in vivo antisense effect of AsODN-loaded chitosan nanoparticles after topical application. AsODN-loaded chitosan nanoparticles were topically applied to Sprague Dawley rats (adult and baby). At 1, 3, 6, 9, and 12 days posttransfection, animals' skin samples were taken for measurement of beta-galactosidase (beta-Gal) expression and histological control. After topical application of AsODN-loaded chitosan nanoparticles in different doses, beta-Gal expression reduced significantly. Highest inhibition was observed after 6 days of transfection of nanoparticles. Free AsODNs exhibited 35% of beta-Gal inhibition on the first day. beta-Gal expression was inhibited in approximately 82-85% with transfection of nanoparticles containing 30 mg AsODNs at 6 days. The antisense effect of AsODN-loaded chitosan nanoparticle in baby skin was evaluated at 6 days: 77-86% of beta-Gal suppression was measured and differences between the doses were not significant. Thus, chitosan nanoparticles are useful carrier for delivery of AsODNs into skin cells of rats and may be used for topical application on human skin.