US 12,295,699 B2
Multiple CEST contrast imaging of nose-to-brain drug delivery using CT-contrast agent-loaded liposomes
Wai Yan Chan, Kowloon (HK); Jianpan Huang, Kowloon (HK); and Lok Hin Law, Kowloon (HK)
Assigned to CITY UNIVERSITY OF HONG KONG, Kowloon (HK)
Filed by CITY UNIVERSITY OF HONG KONG, Kowloon (HK)
Filed on Oct. 4, 2023, as Appl. No. 18/481,196.
Claims priority of provisional application 63/413,137, filed on Oct. 4, 2022.
Prior Publication US 2024/0115136 A1, Apr. 11, 2024
Int. Cl. A61B 5/00 (2006.01); A61B 5/055 (2006.01); A61B 6/00 (2006.01); A61K 9/1271 (2025.01); A61K 49/04 (2006.01); A61M 11/00 (2006.01)
CPC A61B 5/0042 (2013.01) [A61B 5/055 (2013.01); A61B 6/481 (2013.01); A61K 9/1271 (2013.01); A61K 49/0438 (2013.01); A61M 11/00 (2013.01)] 13 Claims
OG exemplary drawing
 
1. A method of delivering a drug to the brain of a subject and monitoring the distribution of the drug therein comprising:
(a) intranasally administering a first and second liposomes respectively loaded with the drug and a computed tomography (CT) contrast agent therein to the subject;
(b) subjecting the brain of the subject of step (a) to a magnetic resonance imaging (MRI) scan; and
(c) measuring chemical exchange saturation transfer (CEST) signals during the MRI scan in both olfactory bulb (OB) and frontal lobe (FL) regions at 1.2 ppm, 4.3 ppm, and −3.4 ppm, respectively;
wherein,
each of the first and second liposomes in step (a) independently comprises a hydrophilic core; and a lipid bilayer shell formed by a cholesterol, and one or more of a phospholipid optionally modified with a polyethylene glycol (PEG), in which the PEG-modified phospholipid is arranged in the manner that the PEG are disposed outside the lipid bilayer shell, and the PEG is at least 7% by weight based on the total weight of the first or second liposomes;
the drug and the CT contrast agent are respectively disposed within the hydrophilic cores of the first and second liposomes; and
an increase in the CEST signals respectively measured at about 1.2 ppm, 4.3 ppm, and −3.4 ppm in step (c) represent the presence of the PEG, the CT contrast agent, and the phospholipid bilayer of the first or second liposomes in the OB and FL regions.