Fig. 5.

Utility of the first-pass effect in tissue targeting. A: Intravenous (IV) infusion of ICAM-targeted nanocarriers (NC) results in a large portion of the dose being deposited in the lungs. On the other hand, infusion into the internal carotid artery bypasses the lung first pass and permits delivery to the brain. B: Ex vivo adsorption of untargeted NC onto RBC, termed RBC hitchhiking (RBC–H), allows transfer of NC to endothelium in the first capillary downstream of the injection site. This technology has been shown to increase delivery to several tissues by varying the injection site. Additional abbreviations used in figure: ICA (internal carotid artery), CCA (common carotid artery). Figures adapted from [231,232].