Multiple CEST contrast imaging of nose-to-brain drug delivery using CT-contrast agent-loaded liposomes

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.