Polyalkylcyanoacrylate nanoparticles as polymeric carriers for antisense oligonucleotides.
Adsorption of oligothymidylates on polyisobutyl- or polyisohexylcyanoacrylate nanoparticles was achieved in the presence of hydrophobic cations such as tetraphenylphosphonium chloride or quaternary ammonium salts. Results suggested that oligonucleotide adsorption on the nanoparticles was mediated by the formation of ion pairs between the negatively charged phosphate groups of the nucleic acid chain and the hydrophobic cations. The adsorption efficiency of oligonucleotide-cation complexes on nanoparticles was found to be highly dependent upon several parameters: oligonucleotide chain length, nature of the cyanoacrylic monomer, hydrophobicity of cations used as ion-pairing agents, and ionic concentration of the medium. Carrier capacity of polyisohexylcyanoacrylate nanoparticles for oligothymidylates (16 nucleotides) complexed with cetyltrimetylammonium bromide in the presence of 0.15 M NaCl was determined to be 5 mumol/g polymer. The in vitro protection of oligothymidylates adsorbed to nanoparticles against degradation by a 3'-exonuclease (snake venom phosphodiesterase) was also demonstrated. These results showed that nanoparticles can be considered as convenient carriers for the protection and delivery of oligonucleotides to cells in culture and for future applications in vivo.
Chavany
C
C
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U 201, CNRS URA 481, Paris, France.
Le Doan
T
T
Couvreur
P
P
Puisieux
F
F
Hélène
C
C
D003487:Cyanoacrylates / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense / Q000378:metabolism*
D003487:Cyanoacrylates; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense