TY - JOUR
T1 - Multiple CEST contrast imaging of nose-to-brain drug delivery using iohexol liposomes at 3T MRI
AU - Law, Lok Hin
AU - Huang, Jianpan
AU - Xiao, Peng
AU - Liu, Yang
AU - Chen, Zilin
AU - Lai, Joseph H.C.
AU - Han, Xiongqi
AU - Cheng, Gerald W.Y.
AU - Tse, Kai Hei
AU - Chan, Kannie W.Y.
N1 - Funding Information:
Research Grants Council: 11102218, PDFS2122-1S01; City University of Hong Kong : 7005210 , 7005433 , 7005626 and 9667198 ; National Natural Science Foundation of China : 81871409 ; Tung Biomedical Science Centre ; Hong Kong Centre for Cerebro-cardiovascular Health Engineering.
Funding Information:
This work was supported by Research Grants Council: 11102218, 11200422, RFS2223-1S02, PDFS2122-1S01, CRF-C1134-20G; ITF-MRP/045/21X; City University of Hong Kong: 7005210, 7005433, 7005626 and 9667198; National Natural Science Foundation of China: 81871409; Tung Biomedical Sciences Centre; Hong Kong Centre for Cerebro-cardiovascular Health Engineering.
Publisher Copyright:
© 2023
PY - 2023/2
Y1 - 2023/2
N2 - Image guided nose-to-brain drug delivery provides a non-invasive way to monitor drug delivered to the brain, and the intranasal administration could increase effective dose via bypassing Blood Brain Barrier (BBB). Here, we investigated the imaging of liposome-based drug delivery to the brain via intranasal administration, in which the liposome could penetrate mucus and could be detected by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) at 3T field strength. Liposomes were loaded with a computed tomography (CT) contrast agent, iohexol (Ioh-Lipo), which has specific amide protons exchanging at 4.3 ppm of Z-spectrum (or CEST spectrum). Ioh-Lipo generated CEST contrasts of 35.4% at 4.3 ppm, 1.8% at −3.4 ppm and 20.6% at 1.2 ppm in vitro. After intranasal administration, these specific CEST contrasts were observed in both olfactory bulb (OB) and frontal lobe (FL) in the case of 10% polyethylene glycol (PEG) Ioh-Lipo. We observed obvious increases in CEST contrast in OB half an hour after the injection of 10% PEG Ioh-Lipo, with a percentage increase of 62.0% at 4.3 ppm, 10.9% at −3.4 ppm and 25.7% at 1.2 ppm. Interestingly, the CEST map at 4.3 ppm was distinctive from that at −3.4 pm and 1.2 ppm. The highest contrast of 4.3 ppm was at the external plexiform layer (EPL) and the region between left and right OB (LROB), while the CEST contrast at −3.4 ppm had no significant difference among all investigated regions with slightly higher signal in olfactory limbus (OL, between OB and FL) and FL, as validated with histology. While no substantial increase of CEST contrast at 4.3 ppm, −3.4 ppm or 1.2 ppm was observed in OB and FL when 1% PEG Ioh-Lipo was administered. We demonstrated for the first time the feasibility of non-invasively detecting the nose-to-brain delivery of liposomes using CEST MRI. This multiple-contrast approach is necessary to image the specific distribution of iohexol and liposome simultaneously and independently, especially when designing drug carriers for nose-to-brain drug delivery.
AB - Image guided nose-to-brain drug delivery provides a non-invasive way to monitor drug delivered to the brain, and the intranasal administration could increase effective dose via bypassing Blood Brain Barrier (BBB). Here, we investigated the imaging of liposome-based drug delivery to the brain via intranasal administration, in which the liposome could penetrate mucus and could be detected by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) at 3T field strength. Liposomes were loaded with a computed tomography (CT) contrast agent, iohexol (Ioh-Lipo), which has specific amide protons exchanging at 4.3 ppm of Z-spectrum (or CEST spectrum). Ioh-Lipo generated CEST contrasts of 35.4% at 4.3 ppm, 1.8% at −3.4 ppm and 20.6% at 1.2 ppm in vitro. After intranasal administration, these specific CEST contrasts were observed in both olfactory bulb (OB) and frontal lobe (FL) in the case of 10% polyethylene glycol (PEG) Ioh-Lipo. We observed obvious increases in CEST contrast in OB half an hour after the injection of 10% PEG Ioh-Lipo, with a percentage increase of 62.0% at 4.3 ppm, 10.9% at −3.4 ppm and 25.7% at 1.2 ppm. Interestingly, the CEST map at 4.3 ppm was distinctive from that at −3.4 pm and 1.2 ppm. The highest contrast of 4.3 ppm was at the external plexiform layer (EPL) and the region between left and right OB (LROB), while the CEST contrast at −3.4 ppm had no significant difference among all investigated regions with slightly higher signal in olfactory limbus (OL, between OB and FL) and FL, as validated with histology. While no substantial increase of CEST contrast at 4.3 ppm, −3.4 ppm or 1.2 ppm was observed in OB and FL when 1% PEG Ioh-Lipo was administered. We demonstrated for the first time the feasibility of non-invasively detecting the nose-to-brain delivery of liposomes using CEST MRI. This multiple-contrast approach is necessary to image the specific distribution of iohexol and liposome simultaneously and independently, especially when designing drug carriers for nose-to-brain drug delivery.
KW - CEST MRI
KW - Iohexol
KW - Liposome
KW - Nose-to-brain drug delivery
KW - Polyethylene glycol
UR - http://www.scopus.com/inward/record.url?scp=85146048417&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2023.01.011
DO - 10.1016/j.jconrel.2023.01.011
M3 - Journal article
C2 - 36623695
AN - SCOPUS:85146048417
SN - 0168-3659
VL - 354
SP - 208
EP - 220
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -