Targeting bone marrow with the help of polyalkylcyanoacrylate nanoparticles

Ciblage de la moelle osseuse à l'aide de nanoparticules de polyalkylcyanoacrylate

S. Gibaud (1) , C. Weingarten , J. P. Andreux , P. Couvreur (2)

1 CITHEFOR - Cibles thérapeutiques, formulation et expertise pré-clinique du médicament
2 PCPB - Physico-chimie, pharmacotechnie, biopharmacie

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.

Domaines: Sciences pharmaceutiques

S. Gibaud, C. Weingarten, J. P. Andreux, P. Couvreur. Ciblage de la moelle osseuse à l'aide de nanoparticules de polyalkylcyanoacrylate. Annales Pharmaceutiques Françaises, 1999, 57 (4), pp.324-31. ⟨hal-00399628⟩