After intravenous injection, the main part of nanoparticles trapped by the
spleen are concentrated in the marginal zone. The first step of this captur
e is the adhesion of the particles to the marginal zone macrophages. As cla
ssical techniques of cell suspension preparation did not allow to isolate w
ithout damage these actively capturing cells, tightly bound to a wed-develo
ped reticular meshwork, we designed a tissue slice incubation method, in or
der to study in vitro the interaction of nanoparticles with these particula
r macrophages, in conditions close to in vivo. In a serum supplemented medi
um, this in vitro model was able to give similar uptake profile than after
intravenous injection of nanoparticles thus proving its validity. Surprisin
gly, no significant decrease of nanoparticles capture was observed when the
medium was depleted from complement, immunoglobulins or proteins affine fo
r heparin, while substitution of serum by purified albumin allowed a near o
ptimal uptake. Addition of competitive ligands for lectin-like receptors di
d not show any clear inhibition of spleen capture. On the other hand, the s
cavenger receptor blocking agents, such as maleylated albumin or polyinosin
ic acid, induced a strong reduction of the spleen nanoparticles uptake. Thu
s, this paper proposes an in vitro binding assay as a reliable method to in
vestigate the spleen capture of a large variety of nanoparticulate drug car
riers. It is also a useful methodology to highlight the interactions betwee
n spleen cells and nanoparticles. The data obtained suggest that capture of
nanoparticles depends on a multifactorial and complex phenomenon involving
for a part albumin and the scavenger receptor.