- Incorporation of drugs into nano-drug delivery systems (nano-DDSs) leads to profound changes in their disposition (distribution and elimination) and pharmacological activity (magnitude of desired and adverse effects). Nano-DDSs of different types (liposomes, particles, drug conjugates, etc.) and of different composition are intensively investigated nowadays in pre-clinical and clinical settings. Specifically, the relationships between the nano-DDSs composition, efficiency of their targeting to the intended site of action, and the magnitude of the desired vs. adverse effects are examined. In this chapter, the pathways of nano-DDSs disposition at the systemic, local, and intracellular levels are described, and the formulation properties that affect the drug targeting efficiency at each of these levels are discussed. Complexity of the nano-DDSs disposition pathways and limitations of drug targeting approaches are illustrated using specific examples: (1) delivery of antigenic peptides to the endoplasmic reticulum (ER) of the antigen presenting cells using PLGA-based nano-DDSs for the purpose of anti-cancer vaccination, (2) delivery of analgesic peptides to the brain using bolavesicle-based nano-DDSs.