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Εξειδίκευση τύπου : Άρθρο σε επιστημονικό περιοδικό
Τίτλος: Polyplexes based on cationic polymers with strong nucleic acid binding properties
Δημιουργός/Συγγραφέας: Varkouhi, Amir K.
Mountrichas, Grigoris
Schiffelers, Raymond M.
Lammers, Twan
Storm, Gert
[EL] Πίσπας, Στέργιος[EN] Pispas, Stergiossemantics logo
Hennink, Wim E.
Εκδότης: Elsevier Science Bv
Τόπος έκδοσης: Amsterdam
Ημερομηνία: 2012-03-12
Γλώσσα: Αγγλικά
ISSN: 0928-0987
DOI: 10.1016/j.ejps.2011.09.002
Περίληψη: Cationic polymers have been studied for nucleic acid delivery both in vitro and in vivo. However, many polymer-based formulations suffer from lack of stability in biologic fluids due to interactions with anionic biomacromolecules such as proteins and polysaccharides. Likely, the stronger the electrostatic interactions between a cationic polymer and nucleic acids, the higher the stability of the polyplexes in biologic fluids will be. To get evidence for this hypothesis, quaternized poly[3,5-bis(dimethylaminomethylene)-p-hydroxyl styrene] (QNPHOS) with two permanently charged cationic sites per monomer unit as well as its block copolymer with PEG were synthesized and compared with the standard transfectant pDMAEMA, in terms of nucleic acid binding strength, gene silencing and transfection activities of the complexes which these polymers form with siRNA and plasmid DNA, respectively. It was shown that siRNA complexes based on QNPHOS and QNPHOS-PEG dissociate in the presence of a fourfold higher heparin concentration than necessary to destabilize pDMAEMA complexes. Under the same conditions, complexes of DNA and QNPHOS or QNPHOS-PEG did not show any dissociation, in contrast to pDMAEMA polyplexes. The DNA polyplexes based on QNPHOS or QNPHOS-PEG did not show transfection activity, which might be ascribed to their high physicochemical stability. On the other hand, siRNA complexes based on QNPHOS and QNPHOS-PEG showed a low cytotoxicity and an improved siRNA delivery and high gene silencing activity, even higher than those based on pDMAEMA. This might be due to the excellent binding characteristics of QNPHOS and QNPHOS-PEG to siRNA which in turn is ascribed to the presence of two permanently charged cationic groups per monomer unit. Based on the results of this study, it is concluded that formation of strong siRNA complexes with polymers containing double charges per monomer is advantageous.
Τίτλος πηγής δημοσίευσης: European Journal of Pharmaceutical Sciences (incorporating Pharmaceutica Acta Helvetiae)
Τόμος/Κεφάλαιο: 45
Τεύχος: 4
Σελίδες: 459-466
Θεματική Κατηγορία: [EL] Φαρμακευτική[EN] Pharmacy and materia medicasemantics logo
Λέξεις-Κλειδιά: siRNA
Plasmid DNA
Delivery
Polymeric vectors
Gene silencing
Transfection
Αξιολόγηση από ομότιμους (peer reviewed): Ναι
Κάτοχος πνευματικών δικαιωμάτων: © 2011 Elsevier B.V. All rights reserved.
Ηλεκτρονική διεύθυνση περιοδικού (link) : http://www.sciencedirect.com/science/journal/09280987
Σημειώσεις: Special Issue SI
Εμφανίζεται στις συλλογές:Ινστιτούτο Θεωρητικής και Φυσικής Χημείας (ΙΘΦΧ) - Επιστημονικό έργο

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