Nanoparticulate systems for the delivery of antisense oligonucleotides.
Antisense oligonucleotides are molecules that are able to inhibit gene expression being therefore potentially active for the treatment of viral infections or cancer. However, because of their poor stability in biological medium and their weak intracellular penetration, colloidal drugs carriers such as nanoparticles were developed for the delivery of oligonucleotides (ODN). ODN associated to nanoparticles were shown to be protected against degradation and to penetrate more easily into different types of cells. As a consequence, nanoparticles were shown to improve the efficiency of ODNs for the inhibition of the proliferation of cells expressing the point mutated Ha-ras gene. In vivo, polyalkylcyanoacrylate (PACA) nanoparticles were able to efficiently distribute the ODNs to the liver whereas the alginate nanosponges could concentrate the ODNs in the lungs. Finally, ODN loaded to PACA nanoparticles were able to improve in mice, the treatment of RAS cells expressing the point mutated Ha-ras gene.
Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, URA CNRS 8612, Faculté de Pharmacie, 5, Rue Jean-Baptiste Clément, 99296 Châtenay-Malabry, France.
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Lambert
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Fattal
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Couvreur
D000818:Animals; D002214:Capsules; D003487:Cyanoacrylates / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D011905:Genes, ras / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020298:U937 Cells
D002214:Capsules; D003487:Cyanoacrylates; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D011108:Polymers; D012333:RNA, Messenger; C057532:polyisohexylcyanoacrylate