Abstract
BackgroundIntranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and directly delivers medication to the brain and spinal cord. However, a device designed specifically for olfactory delivery has not yet been found.MethodsIn this study, a new delivery method was proposed that utilized electrophoretic forces to guide drug particles to the olfactory region. The feasibility of this method was numerically evaluated in both idealized 2-D and anatomically accurate 3-D nose models. The influence of nasal airflow, electrode strength, and drug release position were also studied on the olfactory delivery efficiency.FindingsResults showed that by applying electrophoretic forces, the dosage to the olfactory region was significantly enhanced. In both 2-D and 3-D cases, electrophoretic-guided delivery achieved olfactory dosages nearly two orders of magnitude higher than that without electrophoretic forces. Furthermore, releasing drugs into the upper half of the nostril (i.e., partial release) led to olfactory dosages two times higher than releasing drugs over the entire area of the nostril. By combining the advantages of pointed drug release and appropriate electrophoretic guidance, olfactory dosages of more than 90% were observed as compared to the extremely low olfactory dosage (<1%) with conventional inhaler devices.ConclusionResults of this study have important implications in developing personalized olfactory delivery protocols for the treatment of neurological disorders. Moreover, a high sensitivity of olfactory dosage was observed in relation to different pointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery.
Highlights
The Blood-Brain-Barrier (BBB) has forestalled the use of many new genetically engineered drugs for treating central nervous system (CNS) disorders such as Alzheimer’s disease [1], paraplegia [2], and migraine headache [3]
A high sensitivity of olfactory dosage was observed in relation to different pointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery
The objectives of this study are to (1) develop a computational fluid dynamics (CFD) model of electrophoretic-guided drug delivery; (2) numerically evaluate the feasibility of electrophoretic focusing in three quadrupole designs; (3) numerically evaluate the efficiency of the electrophoretic-guided drug delivery in both idealized 2-D and physiologically realistic 3-D nose models; and (4) identify the optimal layout and operating parameters of the electrodes
Summary
The Blood-Brain-Barrier (BBB) has forestalled the use of many new genetically engineered drugs for treating central nervous system (CNS) disorders such as Alzheimer’s disease [1], paraplegia [2], and migraine headache [3]. Direct noseto-brain drug delivery circumvents the BBB and has multiple advantages over conventional intravenous delivery methods. These advantages include ease of administration, rapid onset of action, and avoidance of first-pass metabolism [5,6]. Demonstration of its clinical feasibility is still in adolescence due to a lack of devices that effectively deliver medication to the olfactory region. The limitations of conventional nasal devices are obvious; only a very small fraction of therapeutic agents deposit in the olfactory region and enter the brain. It is critical to search for more effective methods to deliver drugs to the olfactory region. Intranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and directly delivers medication to the brain and spinal cord. A device designed for olfactory delivery has not yet been found
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