Lipid Nanocarriers for Intracellular Delivery

Lipid Nanocarriers for Intracellular Delivery

Clara Bernard Fernandes (SVKM's NMIMS, India), Divya Suares (SVKM'S NMIMS, India) and Vivek Dhawan (SVKM'S NMIMS, India)
DOI: 10.4018/978-1-5225-4781-5.ch006


Recent trends in drug delivery indicate a growing trend to utilize nanotechnology to target diseased tissues with minimal adverse effects. However, in such cases, the biggest challenge encountered by the formulator is the intracellular delivery of the actives. Nevertheless, pharmaceutical nanocarriers have proven to possess distinct advantages for intracellular delivery of therapeutics over conventional approaches. They are versatile in terms of engineering and provide attractive options to deliver encapsulated or conjugated cargoes to cellular targets. In this chapter, the authors discuss important aspects of lipid-based nanocarriers for intracellular drug targeting. The chapter provides insight of different pathways to internalize lipid nanocarriers and the physicochemical factors affecting the intracellular fate of nanocarriers. Further, the chapter provides details of different types of lipid-based nanocarriers that have been explored for intracellular delivery in infectious diseases as well as cancer.
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2. Mechanism Of Cellular Uptake Of Nanocarriers

It is believed that for small molecules, primary pathway for cellular entry is through passive diffusion or active transport. However, for nanomedicines the predominant route into cells is endocytosis (Kou, Sun, Zhai, & He, 2013). Endocytosis is broadly classified into phagocytosis and pinocytosis. Phagocytosis is generally associated with macrophages, monocytes and polymorphonuclear neutrophils (PMNs) while pinocytosis occurs in all cells (Wang, Byrne, Napier & DeSimone, 2011) (Figure 1).

Figure 1.

Various mechanisms of cellular uptake of nanocarriers

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).

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