TY - JOUR
T1 - Comparison of Focused Ultrasound-Mediated Intranasal Delivery and Focused Ultrasound-Induced Blood-Brain Barrier Disruption in the Delivery of Gold Nanoclusters to the Brainstem
AU - Ye, Dezhuang
AU - Zhuang, Xiaohui
AU - Yue, Yimei
AU - Taylor, Sara
AU - Tai, Yuan Chuan
AU - Rubin, Joshua B.
AU - Liu, Yongjian
AU - Chen, Hong
N1 - Publisher Copyright:
© 2018 IEEE.
PY - 2018
Y1 - 2018
N2 - Focused ultrasound-enabled intranasal brain drug delivery (FUSIN)utilizes the nose-to-brain pathway for drug administration and FUS in combination with microbubbles for enhancing the accumulation of the administered drugs at the FUS-targeted brain location. FUSIN is different from the established FUS-induced BBB disruption (FUS-BBBD)technique. The objective of this study was to compare the delivery efficiency, systemic exposure, and delivery pathways of FUSIN and FUS-BBBD. Taxes red-labeled gold nanoclusters (TR-AuNCs)were used as the model agent and FUS was targeted at the brainstem. Mice were divided into four groups: FUSIN, FUS-BBBD, IN only, and IV only. The delivery efficiency of TR-AuNCs to the mouse brain and exposure to other major organs, as well as the blood, nasal tissue, and trigeminal nerve, were quantified using inductively coupled plasma-mass spectrometry (ICP-MS)analysis of Au concentration. It was found that FUSIN achieved one order of magnitude higher delivery efficiency and one order of magnitude lower systemic exposure in major organs except stomach and intestines than FUS-BBBD. It also verified that FUSIN delivered the AuNCs through the nose-to-brain pathway, while FUS-BBBD utilized the blood-to-brain pathway. These findings suggested that FUSIN is a promising technique for noninvasive and localized brain drug delivery with minimized systemic exposure.
AB - Focused ultrasound-enabled intranasal brain drug delivery (FUSIN)utilizes the nose-to-brain pathway for drug administration and FUS in combination with microbubbles for enhancing the accumulation of the administered drugs at the FUS-targeted brain location. FUSIN is different from the established FUS-induced BBB disruption (FUS-BBBD)technique. The objective of this study was to compare the delivery efficiency, systemic exposure, and delivery pathways of FUSIN and FUS-BBBD. Taxes red-labeled gold nanoclusters (TR-AuNCs)were used as the model agent and FUS was targeted at the brainstem. Mice were divided into four groups: FUSIN, FUS-BBBD, IN only, and IV only. The delivery efficiency of TR-AuNCs to the mouse brain and exposure to other major organs, as well as the blood, nasal tissue, and trigeminal nerve, were quantified using inductively coupled plasma-mass spectrometry (ICP-MS)analysis of Au concentration. It was found that FUSIN achieved one order of magnitude higher delivery efficiency and one order of magnitude lower systemic exposure in major organs except stomach and intestines than FUS-BBBD. It also verified that FUSIN delivered the AuNCs through the nose-to-brain pathway, while FUS-BBBD utilized the blood-to-brain pathway. These findings suggested that FUSIN is a promising technique for noninvasive and localized brain drug delivery with minimized systemic exposure.
KW - Blood-brain barrier
KW - Drug delivery
KW - Focused ultrasound
KW - Intranasal
KW - Nanoparticle
KW - Pons
UR - http://www.scopus.com/inward/record.url?scp=85062505641&partnerID=8YFLogxK
U2 - 10.1109/ULTSYM.2018.8580097
DO - 10.1109/ULTSYM.2018.8580097
M3 - Conference article
AN - SCOPUS:85062505641
SN - 1948-5719
VL - 2018-January
JO - IEEE International Ultrasonics Symposium, IUS
JF - IEEE International Ultrasonics Symposium, IUS
M1 - 8580097
T2 - 2018 IEEE International Ultrasonics Symposium, IUS 2018
Y2 - 22 October 2018 through 25 October 2018
ER -