In vitro evaluation of nanoparticles spleen capture

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.