Radiopaque nanoparticles for medical imaging
View Patent ↗The present disclosure features imaging media including a contrast agent encapsulated within a biodegradable nanoparticle matrix. The particles are sized such that they avoid excretion via urinary excretion (e.g., at least 5 nm in diameter) during an imaging procedure or an image-guided procedure. Instead, the particles are predominantly removed from circulation by the reticuloendothelial system of the liver. This results in a buildup of contrast agent in the liver, allowing for a highly specific imaging modality for liver imaging. Further, the bulk of the imaging media is excreted into the bowel, reducing in-vivo toxicity of the imaging media. Finally, because of their size, the nanoparticles of the imaging media have a higher circulation half-life.
1 . An imaging media comprising:
a) a nanoparticle comprising a diameter of from about 10 nm to about 650 nm and a biodegradable matrix, wherein the biodegradable matrix does not comprise a metal matrix; and
b) a plurality of sub-nanoparticles encapsulated within an interior of the biodegradable matrix of the nanoparticle, wherein each sub-nanoparticle of the plurality of sub-nanoparticles comprises:
(i) a biodegradable matrix; and
(ii) a contrast agent within an interior of the biodegradable matrix of the sub-nanoparticle,
wherein:
the contrast agent is a nonionic or ionic contrast agent comprising iodine as the sole contrast agent and the concentration of the contrast agent in the imaging media is from 5 mg of iodine per 1 mL of the imaging media to 200 mg of iodine per 1 mL of the imaging media.
2 . The imaging media of claim 1 , wherein the biodegradable matrix of the nanoparticle comprises a polymer matrix.
3 . The imaging media of claim 2 , wherein the polymer matrix is or comprises hyaluronic acid (HA), polyethylene glycol diacrylate (PEGDA), polyglycolic acid (PGA), polylactic acid (PLA), poly(lactic-co-glycolic acid) (PLGA), Collagen, Gelatin, carboxymethyl chitosan (CCN), carboxymethyl cellulose (CMC), phospholipids, a polysaccharide, or a combination thereof.
4 . The imaging media of claim 1 , wherein the nanoparticle is spherical, elliptical, rod-shaped, cylindrical, prismatic, or irregular.
5 . The imaging media of claim 1 , wherein the nanoparticle further comprises a coating on the exterior surface of the biodegradable matrix.
6 . The imaging media of claim 5 , wherein the coating is hydrophilic.
7 . The imaging media of claim 5 , wherein the coating is a polymer coating.
8 . The imaging media of claim 7 , wherein the polymer coating is polyglucose sorbitol carboxymethyl ether or polyethylene glycol (PEG).
9 . The imaging media of claim 5 , wherein the coating is from about 1 nm to about 100 nm thick.
10 . The imaging media of claim 1 , wherein the biodegradable matrix of the sub-nanoparticle comprises hyaluronic acid (HA), polyethylene glycol diacrylate (PEGDA), polyglycolic acid (PGA), polylactic acid (PLA), poly(lactic-co-glycolic acid) (PLGA), Collagen, Gelatin, carboxymethyl chitosan (CCN), carboxymethyl cellulose (CMC), phospholipids, a polysaccharide, or a combination thereof.
11 . The imaging media of claim 1 , wherein the sub-nanoparticle and the nanoparticle comprise an identical material.
12 . The imaging media of claim 1 , wherein the sub-nanoparticle is spherical, elliptical, rod-shaped, cylindrical, prismatic, or irregular.
13 . The imaging media of claim 1 , wherein the sub-nanoparticle is substantially spherical and the diameter of the sub-nanoparticle is from about 1 nm to about 30 nm.
14 . The imaging media of claim 1 , wherein the contrast agent is a nonionic contrast agent selected from iodixanol, iohexol, iohexol related compound B, diatrizoic acid, or a combination thereof.
15 . The imaging media of claim 1 , wherein the contrast agent is an ionic contrast agent selected from the group consisting of a diatrizoate salt or an iothalamate salt.
16 . A pharmaceutical composition comprising the imaging media of claim 1 and a pharmaceutically acceptable excipient.
17 . The pharmaceutical composition of claim 16 , wherein the excipient is a polyol, a polyether, salcaprozate sodium, or sodium caprate, and wherein the polyether is polyethylene glycol.
18 . A method of imaging biological tissue in a subject comprising administering to the subject the imaging media of claim 1 or a pharmaceutical composition comprising the imaging media and detecting the imaging media in the biological tissue.
19 . The method of claim 18 , wherein the biological tissue is an organ, wherein the organ is the liver.
20 . The method of claim 18 , wherein the imaging media or pharmaceutical composition is administered directly to the biological tissue or administered intravascularly.
21 . The method of claim 18 , wherein the detecting comprises using X-ray imaging, wherein the X-ray imaging is fluoroscopy or computed tomography (CT) imaging.
22 . The method of claim 21 , wherein the imaging media provides an image contrast of at least 10 Hounsfield units in the biological tissue relative to imaging performed in the absence of the imaging media.
23 . The method of claim 18 , further comprising mixing the imaging media and an excipient at the time of administration.
24 . The method of claim 18 , wherein the nanoparticle is provided as a lyophilized powder, and the method further comprises hydrating, suspending, or solvating the nanoparticle prior to administration.
25 . A kit comprising the imaging media of claim 1 or a pharmaceutical composition thereof.
26 . The kit of claim 25 , wherein the imaging media and the excipient are provided separately and the imaging media is provided as a lyophilized powder.
27 . The kit of claim 25 , further comprising a mixer and/or a puncture set.
28 . The pharmaceutical composition of claim 16 , wherein the iodine is present in the pharmaceutical composition at a concentration from about 5 mg/mL to about 100 mg/mL.