The realization of maybe future, more complex

liposome structures with advanced efficacy will to a great extent dependent on those achievements.
Mononuclear phagocytes such as monocytes, macrophages, and dendritic cells are intrinsically involved in innate immunity. As the designation denotes, the chief role of these cells is phagocytosis whereby cells will engulf and destroy apoptotic cells, pathogens, and other targets. This occurs either through employing opsonin receptor-dependent CT99021 ic50 mechanisms via complement- and Fc-receptors, or opsonin receptor-independent mechanisms via lectin-receptors, scavenger receptors, stearylamine receptors or CD14 [1]. Due Inhibitors,research,lifescience,medical to its pivotal Inhibitors,research,lifescience,medical role in inflammation, the mononuclear phagocytic system (MPS) is an important target for drug delivery to treat disease. For certain diseases such as chronic obstructive pulmonary disease (COPD), asthma, atherosclerosis, and

cancer [2–4] and for pathogenic infections including tuberculosis [5], human immunodeficiency virus (HIV), and Leishmaniasis Inhibitors,research,lifescience,medical [6], the inflammatory process is a key driver of both disease progression as well as pathogenesis. Thus strategies aimed at targeting the MPS are highly attractive. In general however these cells are reputed to be difficult targets [7], particularly where intracellular delivery of the active is required such as for gene delivery [8]. Therefore the development of delivery systems that can target Inhibitors,research,lifescience,medical monocytes/macrophages intracellularly is crucial and could potentially open up new treatment paradigms for a range of diseases. Liposomes are the most widely investigated delivery system for phagocyte-targeted therapies providing advantages such as low immunogenicity, biocompatibility, cell specificity and drug protection. However, there are also shortcomings such as poor scale-up, cost, short shelf life, and in some cases toxicity and off target effects. Parenterally administered liposomes are naturally

Inhibitors,research,lifescience,medical cleared by the MPS. Liposomal delivery over systems targeting other cell types outside the MPS are modified to evade phagocytosis; for example, “stealth liposomes” include poly-ethylene-glycol (PEG) into their formulations to shield the liposomes from the MPS and increase their circulatory lifespan [9]. Consequently, numerous studies have been carried out to develop formulations that avoid monocyte/macrophage clearance, the corollary of which is that there is now greater knowledge of the mechanisms of binding and uptake that can be harnessed for drug targeting to monocyte/macrophage cells. 2. Monocytes and Macrophages Cell origin, lineage, and function in the MPS are complex and remain under considerable investigation.