Polyalkylcyanoacrylate nanoparticles as carriers for granulocyte-colony stimulating factor (G-CSF)

• Published in: Journal of controlled release Vol. 52; no. 1; pp. 131 - 139
• Main Authors: Gibaud, S, Rousseau, C, Weingarten, C, Favier, R, Douay, L, Andreux, J.P, Couvreur, P
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 02.03.1998; Elsevier
• Subjects: Animals; Biological and medical sciences; Cyanoacrylates; Cyanoacrylates - administration & dosage; Drug Carriers; Female; General pharmacology; Granulocyte Colony Stimulating Factor, Recombinant; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte-colony stimulating factor (G-CSF); Humans; Life Sciences; Medical sciences; Mice; Nanoparticles; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Recombinant Proteins; Nanoparticles; Drug carriers; Cyanoacrylates; Granulocyte-colony stimulating factor (G-CSF); Pharmaceutical technology; Intravenous administration; Control release polymer; Rodentia; Drug carrier; In vitro; Dose activity relation; In vivo; Vertebrata; Granulocyte colony stimulating factor; Precipitation; Mammalia; Mouse; Alkyl acrylate(cyano) polymer; Animal; Dosage form; Anionic polymerization; Active ingredient; Recombinant protein; Release
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(97)00194-6

The human recombinant granulocyte colony-stimulating factor (rhG-CSF) is largely used in the treatment of neutropenia occurring during chemotherapy. After injection, this glycoprotein distributes through the whole body. Thus, to obtain high and durable bone marrow concentrations, targeting with polyalkylcyanoacrylate nanoparticles was considered. Two methods of preparation were investigated: anionic polymerization and precipitation of the preformed polymer. By anionic polymerization, it was possible to associate more than 66% of rhG-CSF with nanoparticles (polyisobutyl- or polyisohexylcyanoacrylate nanoparticles) when the glycoprotein was added at the end of the polymerization process. It has been shown that the rhG-CSF was mainly adsorbed on the surface of the nanoparticles and most of the colony stimulating activity was conserved. Using precipitation of preformed polyisohexylcyanoacrylate, 90% of rhG-CSF was associated with nanoparticles, the protein being mainly adsorbed onto the nanoparticle surface. In this case, a decrease of the colony stimulating activity was however observed. Whatever the method used, the in vitro release of rhG-CSF from polyisohexylcyanoacrylate nanoparticles, was progressive during 8 h in seric conditions. Nevertheless, using mice as an animal model, it has been shown that the short-term effects of intravenously injected rhG-CSF were not increased by its association with polyisohexylcyanoacrylate nanoparticles.