There are six classes of SRs with A, B, and D as the most likely participants in liposome recognition [53]. However, not all phagocytes have the same affinity for these anionic lipids. According to Foged et al., PS and PG liposomes were found to have minimal association with human monocyte- and bone marrow-derived dendritic cells [54]. In addition PS is a non-bilayer lipid (along with phosphatidylethanolamine;

PE) which is frequently used in the development of pH-sensitive and fusogenic Inhibitors,research,lifescience,medical liposomes promoting intracellular drug delivery [51]. For instance, liposomes composed of DOPE and PS have been assessed as pH-sensitive carriers of plasmid DNA to RAW 264.7 alveolar macrophages [55]. Recently Andreakos et al. developed a novel amphoteric liposome

for the delivery of antisense oligonucleotides to sites of inflammation in experimental arthritis [56]. The novel formulation known as Nov038 is cationic at low pH and anionic at neutral pH, facilitating complexation Inhibitors,research,lifescience,medical to nucleic acids and avoiding nonspecific blood interactions, respectively. The group reported targeted delivery to sites of inflammation as well as blood, liver, spleen, and inguinal lymph node mononuclear cells. In addition, Nov038 administration was well tolerated with efficient antisense Inhibitors,research,lifescience,medical oligonucleotide delivery in vivo. 3.2. Ligands In addition to controlling the physicochemical properties of liposomes to enhance targeting, ligands can be incorporated into liposome formulations to specifically target monocytes, macrophages, and dendritic Inhibitors,research,lifescience,medical cells. Using a ligand targeting strategy for liposome drug delivery has the advantages of potentially

increasing target specificity and avoiding the need for cationic lipids to trigger intracellular delivery. A multitude of ligands are currently being assessed including peptides, antibodies, proteins, polysaccharides, glycolipids, glycoproteins, and lectins which make use of mononuclear phagocytes characteristic receptor expression and phagocytic innate processes Inhibitors,research,lifescience,medical (Figure 1 and Table 1). Here we will briefly look at three of the most commonly studied systems peptide, antibody, and lectin directed delivery. Levetiracetam 3.2.1. Peptides Cell targeting peptides (CTPs) and cell APO866 penetrating peptides (CPPs) have been conjugated to liposomes to improve cell-specific targeting and cell uptake, respectively, to a range of cell types [57]. Peptide sequences such as GGPNLTGRW (GGP-peptide) have been shown to selectively associate with neutrophils and monocytes [58, 59]. GGP-peptide-coated liposomes, with 500 external ligands per liposome, show 30.9 times greater association to monocytes than uncoated liposomes [58]. Arg-Gly-Asp (RGD) peptide has also been incorporated into liposome formulations to target integrin receptors expressed by monocytes [29, 60, 61] (Figure 1).