Lipid bilayer carrier for drugs or imaging agents

Patent metadata

Field	Value
Publication number	US-9642802-B2
Application number	US-201113809469-A
Country	US
Kind code	B2
Filing date	Jul 8, 2011
Priority date	Jul 13, 2010
Publication date	May 9, 2017
Grant date	May 9, 2017

Abstract

Disclosed are carriers for drugs and/or MR imaging agents having a lipid bilayer shell comprising a phospholipid having two terminal alkyl chains, one being a short chain having a chain length of at most seven carbon atoms, the other being a long chain having a chain length of at least fifteen carbon atoms. The mixed long/short chain phospholipids serve to tune the release properties of the carrier. Preferred phospholipids are phosphatidylcholines.

First claim

The invention claimed is:

1. A composition comprising a thermosensitive carrier having a semipermeable lipid bilayer shell, wherein the semipermeable lipid bilayer comprises a phospholipid having two terminal alkyl chains, one being a short chain having a chain length of at most five carbon atoms, the other being a long chain having a chain length of at least fifteen carbon atoms.

2. The composition of claim 1 , wherein a difference in length between the short chain and the long chain is between eleven and sixteen carbon atoms.

3. The composition of claim 1 , wherein the long chain has a length of at least sixteen carbon atoms.

4. The composition of claim 3 , wherein the long chain has at most twenty carbon atoms.

5. The composition of claim 1 , wherein the long chain has at most twenty carbon atoms.

6. The composition of claim 1 , wherein the long chain has at most thirty carbon atoms.

7. The composition of claim 1 , wherein the phospholipid is selected from the group consisting of phospholipids satisfying formula (I) and phospholipids satisfying formula (II),

wherein R is an alkyl chain of fifteen to thirty carbon atoms, and n is an integer of 1 to 4.

8. The composition of claim 7 , wherein R is selected from the group consisting of C 15 H 31 and C 17 H 35 , and n is 1 to 4.

9. The composition of claim 1 , further comprising at least one drug substance.

10. The composition of claim 1 , further comprising at least one magnetic resonance imaging (MRI) contrast enhancing substance.

11. The composition of claim 1 , further comprising:
at least one drug substance, and
at least one magnetic resonance imaging (MRI) contrast enhancing substance.

12. The composition of claim 1 , further comprising a substance contained within the shell, wherein the carrier is configured for the in vivo release of the substance, and wherein the substance is selected from the group consisting of drugs, MRI contrast enhancing substances, and combinations thereof.

13. The composition of claim 1 , wherein a membrane of the carrier includes a paramagnetic agent which is not a chemical shift reagent.

14. The composition of claim 13 , wherein the carrier is aspherical.

15. The composition of claim 13 , wherein the paramagnetic agent includes an amphiphilic compound comprising a lanthanide complex and having an apolar tail.

16. The composition of claim 1 , further comprising a water solution of a paramagnetic shift reagent encapsulated within an interior compartment defined by the shell.

17. A method for magnetic resonance imaging (MRI) guided delivery of a drug to a subject, the method comprising:
administering to the subject a thermosensitive carrier comprising a semipermeable lipid bilayer shell, wherein the semipermeable lipid bilayer comprises a phospholipid having two terminal alkyl chains, one being a short chain having a chain length of at most five carbon atoms, the other being a long chain having a chain length of at least fifteen carbon atoms, the thermosensitive carrier carrying a drug and an MRI contrast enhancing substance;
allowing the carrier to release the drug and the MRI contrast enhancing substance; and
rendering a magnetic resonance image using the contrast provided by the contrast enhancing substance.

Assignees

• Langereis Sander
• Gruell Holger
• De Smet Mariska
• Aussems-Custers Erica Maria Gerarda
• Lub Johan
• Koninklijke Philips Nv

Inventors

• Langereis Sander
• Gruell Holger
• De Smet Mariska
• Aussems-Custers Erica Maria Gerarda
• Lub Johan

Classifications

• A61K49/1812

  liposomes, polymersomes, e.g. immunoliposomes · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K49/106

  the complex-forming compound being cyclic, e.g. DOTA · CPC title

• A61K41/0028

  Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds · CPC title

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title