Lipid-based nanoparticles
Lipid-based nanoparticle compositions are provided. The compositions generally comprise lipid-hydrophilic polymer-amyloid binding ligand conjugates, and may be liposomal compositions. The compositions, including the liposomal compositions, may be useful for imaging and/or the treatment of amyloid-β plaque deposits characteristic of Alzheimer's Disease.
1. A liposomal composition, comprising:
a membrane, comprising:
a first phospholipid;
cholesterol;
a second phospholipid, the second phospholipid being derivatized with a polymer;
a third phospholipid, the third phospholipid being a phospholipid-polymer-aromatic compound conjugate, the phospholipid-polymer-aromatic compound conjugate being represented by:
wherein: PL is a phospholipid; AL is an aliphatic linkage; and PEG is a polyethylene glycol polymer; and
a nonradioactive magnetic resonance imaging (MRI) contrast enhancing agent at least one of encapsulated by or bound to the membrane.
2. The liposomal composition of claim 1 , wherein AL comprises one or more of: a carbamate linkage and an amide linkage.
3. The liposomal composition of claim 1 , the phospholipid-polymer-aromatic compound conjugate comprising a compound represented by:
wherein n represents a degree of polymerization of the polyethylene glycol polymer between about 10 to about 100.
4. The liposomal composition of claim 3 , wherein n is about 30 to about 80.
5. The liposomal composition of claim 1 , the phospholipid-polymer-aromatic compound conjugate comprising a compound represented by:
wherein n is about 10 to about 100.
6. The liposomal composition of claim 1 , wherein the nonradioactive MRI contrast enhancing agent comprises gadolinium.
7. The liposomal composition of claim 1 , comprising:
DPPC as the first phospholipid;
the cholesterol;
DSPE-AL-mPEG-2000 as the second phospholipid;
the third phospholipid, comprising a compound represented by:
wherein n is about 10 to about 100; and
the nonradioactive magnetic resonance imaging (MRI) contrast enhancing agent comprising Gd-DTPA-BSA.
8. A method for imaging amyloid deposits in a patient, the method comprising:
introducing into the patient a detectable quantity of a liposomal composition comprising:
a membrane, comprising:
a first phospholipid;
cholesterol;
a second phospholipid, the second phospholipid derivatized with a polymer; and
a third phospholipid, the third phospholipid being a phospholipid-polymer-aromatic compound conjugate represented by:
wherein: PL is a phospholipid; AL is an aliphatic linkage; and
PEG is a polyethylene glycol polymer; and
a nonradioactive magnetic resonance imaging (MRI) contrast enhancing agent at least one of encapsulated by or bound to the membrane;
allowing sufficient time for the liposomal composition to be associated with one or more amyloid deposits; and
detecting the liposomal composition associated with the one or more amyloid deposits.
9. The method of claim 8 , wherein the nonradioactive MRI contrast enhancing agent comprises gadolinium.
10. The method of claim 8 , wherein the detecting comprises detecting using magnetic resonance imaging.
11. The method of claim 8 , wherein AL comprises one or more of: an amide linkage and a carbamate linkage.
12. The method of claim 8 , the phospholipid-polymer-aromatic compound conjugate comprising a compound represented by:
wherein n represents a degree of polymerization of the polyethylene glycol polymer of about 10 to about 100.
13. The method of claim 8 , the phospholipid-polymer-aromatic compound conjugate comprising a compound represented by:
wherein n represents a degree of polymerization of the polyethylene glycol polymer of about 10 to about 100.
14. The method of claim 13 , wherein n is about 30 to about 80.
15. The method of claim 8 , the phospholipid-polymer-aromatic compound conjugate comprising a compound represented by:
wherein n is about 10 to about 100.
16. A phospholipid-polymer-aromatic compound conjugate, represented by:
wherein:
PL is a phospholipid;
AL is an aliphatic linkage; and
PEG is a polyethylene glycol polymer.
17. The phospholipid-polymer-aromatic compound conjugate of claim 16 , wherein AL comprises one or more of: an amide linkage and a carbamate linkage.
18. The phospholipid-polymer-aromatic compound conjugate of claim 16 , represented by:
wherein n represents a degree of polymerization of the polyethylene glycol polymer of about 10 to about 100.
19. The phospholipid-polymer-aromatic compound conjugate of claim 16 , comprising one of:
wherein each n is independently about 10 to about 100.
20. The phospholipid-polymer-aromatic compound conjugate of claim 19 , wherein each n is independently about 30 to about 80.