Antisense oligonucleotide delivery with polyhexylcyanoacrylate nanoparticles as carriers.
Polyalkylcyanoacrylate nanoparticles are effective colloidal drug carriers and were prepared by an emulsion polymerization process. Antisense oligonucleotides were loaded on the particles by adsorption. A cationic polymer, DEAE-dextran, was incorporated into the particle matrix or a cationic hydrophobic detergent (CTAB) was used to form a lipophilic oligonucleotide ion pair. Enzymatic digestion of the oligonucleotides was almost quantitatively inhibited by this nanoparticle complex and cellular uptake by different cell lines was significantly enhanced. In vivo the biodistribution of the oligonucleotide nanoparticle complex resulted in targeting of oligonucleotides to the liver. Improvements in antisense treatments with nanoparticles were demonstrated for tumor therapy as well as for antiviral applications.
Zimmer
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Biocenter, Institute for Pharmaceutical Technology, University of Frankfurt, Frankfurt am Main, Germany. Zimmer@em.uni-frankfurt.de
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D003487:Cyanoacrylates; D003637:DEAE-Dextran / Q000737:chemistry; D004337:Drug Carriers; D004655:Emulsions; D018390:Gene Targeting; D008099:Liver / Q000378:metabolism; D018613:Microscopy, Confocal; D008863:Microspheres; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D055672:Static Electricity; D014709:Vero Cells
D019380:Anti-HIV Agents; D003487:Cyanoacrylates; D004337:Drug Carriers; D004655:Emulsions; D016376:Oligonucleotides, Antisense; C042633:poly(hexyl-2-cyanoacrylate); D003637:DEAE-Dextran; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I