Background: Intranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and\ndirectly delivers medication to the brain and spinal cord. However, a device designed specifically for olfactory delivery has\nnot yet been found.\nMethods: In this study, a new delivery method was proposed that utilized electrophoretic forces to guide drug particles to\nthe olfactory region. The feasibility of this method was numerically evaluated in both idealized 2-D and anatomically\naccurate 3-D nose models. The influence of nasal airflow, electrode strength, and drug release position were also studied on\nthe olfactory delivery efficiency.\nFindings: Results showed that by applying electrophoretic forces, the dosage to the olfactory region was significantly\nenhanced. In both 2-D and 3-D cases, electrophoretic-guided delivery achieved olfactory dosages nearly two orders of\nmagnitude higher than that without electrophoretic forces. Furthermore, releasing drugs into the upper half of the nostril\n(i.e., partial release) led to olfactory dosages two times higher than releasing drugs over the entire area of the nostril. By\ncombining the advantages of pointed drug release and appropriate electrophoretic guidance, olfactory dosages of more\nthan 90% were observed as compared to the extremely low olfactory dosage (,1%) with conventional inhaler devices.\nConclusion: Results of this study have important implications in developing personalized olfactory delivery protocols for the\ntreatment of neurological disorders. Moreover, a high sensitivity of olfactory dosage was observed in relation to different\npointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery.
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