Influence of stabilizer, size and physical state of lipid nanoparticles on uptake by THP-1 macrophages.

Macrophages, as cells of the innate immune response, are involved in the pathology of various medical conditions (tumors, intracellular infections, inflammatory diseases etc.). Due to their phagocytic nature, a drug targeting approach to macrophages based on lipid nanoparticles appears promising. Thus, the uptake of different kinds of fluorescently labeled lipid nanoparticles by THP-1 macrophages was assessed with flow cytometry and confocal laser scanning microscopy. 100 nm trilaurin nanoemulsions were produced with different stabilizers to compare the influence of nanoparticle coating on the uptake by THP-1 macrophages. After 2 and 24 h, stabilization with poloxamer 407 led to a significantly reduced uptake compared to a mixture of phosphatidylcholine with sodium glycocholate (PC/SGC) or with the 'eat me' signal phosphatidylserine (PC/PS). The benefit of PC/PS-stabilization over PC/SGC was less pronounced after 24 h, but still significant. A droplet size increase from 100 to 200 nm did not lead to a distinctly higher uptake of the PC/PS-stabilized trilaurin nanodroplets. Changing the matrix lipid of the emulsion from trilaurin to trimyristin (C12 vs. C14 fatty acid chains) resulted in enhanced uptake after 24 h, but not after 2 h. A change in the physical state of the matrix lipid by crystallization of supercooled trimyristin nanoparticles inhibited the cellular uptake of PC/SGC- and P407-stabilized 100 nm particles. A change in particle shape upon crystallization may contribute to this effect. Thus, triglyceride nanoemulsions stabilized with PC/PS and a size of 100 or 200 nm seem most promising regarding the uptake by macrophages.