[Targeting bone marrow with the help of polyalkylcyanoacrylate nanoparticles].
Using a mouse model, we examine drug targeting towards bone marrow. One cytotoxic (doxorubicin) and one stimulating (rhG-CSF), bound to polyalkylcyanoacrylate nanoparticles, were studied. Histological studies, using a fluorescence microscope, showed rapid capture of nanoparticles by bone marrow macrophages and granulocytes as soon as 15 minutes after injection into the blood stream. Doxorubicin nanoparticles, administered at a dose of 11 mg/kg were more toxic than free doxorubicin on all blood and marrow cell lines. Moreover, the choice of the nature of the polymer had an influence on toxicity: doxorubicin polyisohexylcyanoacrylate nanoparticles were more toxic than polyisobutylcyanoacrylate particles. Quantification of doxorubicin in bone marrow has confirmed these results. The bone marrow concentrations observed demonstrated that there was a high level of targeting towards the bone marrow that would be very interesting to use for a stimulating drug. Nevertheless, rhG-CSF nanoparticles did not show better efficacy than free rhG-CSF.
Gibaud
S
S
Laboratoire de Physico-Chimie, Pharmacotechie et Biopharmacie, URA-CNRS 1218, Université Paris XI, Châtenay-Malabry.
Weingarten
C
C
Andreux
J P
JP
Couvreur
P
P
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D003487:Cyanoacrylates; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity; D004337:Drug Carriers; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D011994:Recombinant Proteins
D003487:Cyanoacrylates; D004337:Drug Carriers; D011994:Recombinant Proteins; C057532:polyisohexylcyanoacrylate; D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin