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

TitleMultiple CEST contrast imaging of nose-to-brain drug delivery using iohexol liposomes at 3T MRI
Authors
KeywordsCEST MRI
Iohexol
Liposome
Nose-to-brain drug delivery
Polyethylene glycol
Issue Date2023
Citation
Journal of Controlled Release, 2023, v. 354, p. 208-220 How to Cite?
AbstractImage 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.
Persistent Identifierhttp://hdl.handle.net/10722/328009
ISSN
2023 Impact Factor: 10.5
2023 SCImago Journal Rankings: 2.157
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLaw, Lok Hin-
dc.contributor.authorHuang, Jianpan-
dc.contributor.authorXiao, Peng-
dc.contributor.authorLiu, Yang-
dc.contributor.authorChen, Zilin-
dc.contributor.authorLai, Joseph H.C.-
dc.contributor.authorHan, Xiongqi-
dc.contributor.authorCheng, Gerald W.Y.-
dc.contributor.authorTse, Kai Hei-
dc.contributor.authorChan, Kannie W.Y.-
dc.date.accessioned2023-06-05T06:53:17Z-
dc.date.available2023-06-05T06:53:17Z-
dc.date.issued2023-
dc.identifier.citationJournal of Controlled Release, 2023, v. 354, p. 208-220-
dc.identifier.issn0168-3659-
dc.identifier.urihttp://hdl.handle.net/10722/328009-
dc.description.abstractImage 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.-
dc.languageeng-
dc.relation.ispartofJournal of Controlled Release-
dc.subjectCEST MRI-
dc.subjectIohexol-
dc.subjectLiposome-
dc.subjectNose-to-brain drug delivery-
dc.subjectPolyethylene glycol-
dc.titleMultiple CEST contrast imaging of nose-to-brain drug delivery using iohexol liposomes at 3T MRI-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jconrel.2023.01.011-
dc.identifier.pmid36623695-
dc.identifier.scopuseid_2-s2.0-85146048417-
dc.identifier.volume354-
dc.identifier.spage208-
dc.identifier.epage220-
dc.identifier.eissn1873-4995-
dc.identifier.isiWOS:000925303300001-

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