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Antisense delivery using protamine-oligonucleotide particles
M Junghans1, J Kreuter, A Zimmer
1Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe Universität, Biozentrum, Marie Curie Strasse 9, 60439 Frankfurt am Main, Germany.
Abstract:
Protamine, a polycationic peptide (mol. wt 4000-4500), was evaluated as a potential penetration enhancer for phosphodiester antisense oligonucleotides (ODNs). Unique complexes in the form of nanoparticles were spontaneously formed, which we call 'proticles'. The stability of the particles and the ODNs bound into the proticles was examined in foetal calf serum and cell culture medium. FITC-labelled ODNs bound to protamine showed an increased cellular uptake into human histiocytic lymphoma U 937 cells compared to free ODNs. Proticles significantly decreased cellular growth in a cell proliferation assay using ODNs against the c- myc proto-oncogene.