Electrophoretic particle guidance significantly enhances olfactory drug delivery: a feasibility study.
BACKGROUND
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. However, a device designed specifically for olfactory delivery has not yet been found.


METHODS
In 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.


RESULTS
Results 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.


CONCLUSIONS
Results 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.
Department of Mechanical and Biomedical Engineering, Central Michigan University, Mount Pleasant, Michigan, United States of America.
Jinxiang
J
Xi
Department of Engineering, Calvin College, Grand Rapids, Michigan, United States of America.
Xiuhua A
XA
Si
Department of Engineering, Calvin College, Grand Rapids, Michigan, United States of America.
Rachel
R
Gaide
D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000465:Algorithms; D016503:Drug Delivery Systems / Q000379:methods*; D004586:Electrophoresis; D005240:Feasibility Studies; D006801:Humans; D008954:Models, Biological; D009297:Nasal Mucosa / Q000378:metabolism; D009666:Nose / Q000033:anatomy & histology; D009833:Olfactory Pathways / Q000378:metabolism*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D015203:Reproducibility of Results
D004364:Pharmaceutical Preparations