Abstract
Monocytes/macrophages are phagocytic innate immune cells playing a pivotal role in tissue homeostasis, inflammation, and antitumor immunity in a microenvironment‐dependent manner. By expressing pattern recognition and scavenger receptors on their surface, macrophages selectively take up pathogens, cellular debris, and often—undesirably—drug delivery systems. On the other hand, the propensity of phagocytic cells to internalize particulate drug carriers is used to load them with a cargo of choice, turning the monocytes/macrophages into a diagnostic or therapeutic Trojan horse. Identifying the ideal physicochemical properties of particulate carriers such as liposomes to achieve the most efficient macrophage‐mediated drug delivery has been object of extensive research in the past, but the studies reported so far rely solely on trial‐and‐error approaches. Herein, a design of experiment (DoE) strategy to identify the optimal liposomal formulation is proposed, fully characterized in terms of size, surface charge, and membrane fluidity, to maximize macrophage targeting. The findings are validated using mouse bone marrow‐derived macrophages, a primary preparation modeling in vivo monocyte‐derived macrophages, thus confirming the robustness and versatility of the systematic and iterative approach and suggesting the promising potential of the DoE approach for the design of cell‐targeting delivery systems.
Highlights
Monocytes/macrophages are phagocytic innate immune cells playing a pivotal role in tissue homeostasis, inflammation, and antitumor immunity in a microenvironment-dependent manner
The zeta potential and the particle size were similar for each set of experiments between the liposomes containing the same negatively charged phospholipids (NPLs), whereas the particle charge decreased as the percentage of NPL increased (Figure 1A,B)
We have demonstrated the power of the design of experiment (DoE) strategy for the development of liposomes and its ability to minimize the aforementioned disadvantages through a systematic, iterative screening
Summary
Monocytes/macrophages are phagocytic innate immune cells playing a pivotal role in tissue homeostasis, inflammation, and antitumor immunity in a microenvironment-dependent manner. Specific macropopulating every organ of the body and playing a pivotal role phage targeting is obtained by fine tuning liposome characteristics such as lipid composition,[9] size, and surface charge.[4,10]. Locatelli Theodor Kocher Institute University of Bern interest for their ability to be engulfed by macrophages through SR-mediated endocytosis.[4] Under physiological conditions, PS is preferentially located on the inner leaflet of eukaryotic plasma membrane and in endocytic membranes, whereas phosphocholine (PC) resides more commonly in the outer leaflet. This asymmetrical arrangement is altered when cells undergo
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