Multiple CEST contrast imaging of nose-to-brain drug delivery using iohexol liposomes at 3T MRI

Lok Hin Law; Jianpan Huang; Peng Xiao; Yang Liu; Zilin Chen; Joseph H C Lai; Xiongqi Han; Gerald W Y Cheng; Kai-Hei Tse; Kannie W Y Chan

doi:10.1016/j.jconrel.2023.01.011

Multiple CEST contrast imaging of nose-to-brain drug delivery using iohexol liposomes at 3T MRI

J Control Release. 2023 Feb:354:208-220. doi: 10.1016/j.jconrel.2023.01.011. Epub 2023 Jan 10.

Authors

Affiliations

¹ Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
² Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China.
³ Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States; City University of Hong Kong Shenzhen Research Institute, Shenzhen, China; Tung Biomedical Science Centre, City University of Hong Kong, Hong Kong, China; Hong Kong Centre for Cerebro-cardiovascular Health Engineering, Hong Kong, China. Electronic address: KannieW.Y.C@cityu.edu.hk.

PMID: 36623695
DOI: 10.1016/j.jconrel.2023.01.011

Abstract

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.

Keywords: CEST MRI; Iohexol; Liposome; Nose-to-brain drug delivery; Polyethylene glycol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain
Contrast Media
Drug Delivery Systems
Iohexol*
Liposomes*
Magnetic Resonance Imaging / methods

Substances

Liposomes
Iohexol
Contrast Media