Cationic lipid-protamine-DNA (LPD) complexes for delivery of antisense c-myc oligonucleotides.
In the present study, cationic lipid-peptide-DNA-complexes (LPDs) consisting of AH-Chol-liposomes and protamine-phosphodiester-oligonucleotide-particles (proticles) were introduced as carriers for antisense therapy. The LPDs were physically characterized, and a possible mechanism for adsorption of oligonucleotides (ODNs) was suggested. An increase in stability of ODNs against DNase I and serum nuclease digestion by these carriers was demonstrated. The hydrodynamic diameter increased after incubation with FCS which could be attributed to a protein coating of the particle surface. However, in cell culture medium lower particle sizes of the complexes occurred. In an antisense c-myc in vitro model, the effect of LPDs was tested using U937 cells. The C-MYC level was reduced after treatment of these antisense ODN carrier complexes. Furthermore, no changes in target mRNA concentration of the treated cells was found by reverse transcription and competitive multiplex-PCR.
Junghans
Monika
M
Institute for Pharmaceutical Technology, Biocenter, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Loitsch
Stefan M
SM
Steiniger
Sebastian C J
SC
Kreuter
Jörg
J
Zimmer
Andreas
A
D003470:Culture Media; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D006801:Humans; D008055:Lipids / Q000008:administration & dosage*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D011479:Protamines / Q000008:administration & dosage*; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000032:analysis; D016914:Ribonuclease H / Q000378:metabolism; D020298:U937 Cells
D003470:Culture Media; D008055:Lipids; D016376:Oligonucleotides, Antisense; D011479:Protamines; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D004247:DNA; D016914:Ribonuclease H