Lipid Nanocarriers for Intracellular Delivery

2.1. Phagocytosis

This pathway predominantly relies on recognition and internalization of larger nanocarriers and pathogens. This pathway is characterized by three stepwise related events: 1) recognition of the nanocarriers by opsonization; 2) adhesion of opsonized nanocarriers onto the cell membrane; 3) ingestion of nanocarriers by the cells. For opsonization, various blood components such as proteins (immunoglubulins IgG, IgM), complement components (C3, C4, C5), blood serum proteins (including laminin, fibronectin, etc.) and others are adsorbed onto the nanocarrier surface. Post opsonization, the particles attach to the macrophage surface through Fc receptor (FcR) or complement receptors (CR) or other receptors such as mannose/ fructose and scavenger receptors (Sahay, Alakhova, & Kabanov, 2010). This receptor-ligand interaction results in actin rearrangement and formation of a phagosome (diameter of 0.5 µm-10 mm) which internalizes the nanocarriers in macrophages through attractive forces (i.e., van der Waals, electrostatic, ionic, hydrophobic/ hydrophilic) between the cells and nanoparticles surfaces (Yameen, Choi, Vilos, Swami, Shi, & Farokhzad, 2014). Thereafter, the phagosomes fuse with lysosomes, wherein the nanocarriers are destroyed by acidification and enzymolysis in the lysosomes (Kou, Sun, Zhai, & He, 2013). Although phagocytosis is a deterrent for site-specific targeting of intravenously administered nanocarriers, it has been exploited for targeting macrophages related infections e.g. liposomal and lipidic amphotericin B products (Ambisome, Abelcet and Amphocil) (Duncan & Richardson, 2012).