Liposomal delivery vehicle for hydrophobic drugs

• US 20070014845A1
• Filed: 06/30/2006
• Published: 01/18/2007
• Est. Priority Date: 07/01/2005
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Zhang, Yuanpeng, Luo, Bing, Iyer, Laxmi
• Application Number:
  US11/479,620
• Publication Number:
  US 20070014845A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/724 Cyclodextrins
• CPC Class Codes: A61K 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

A liposome composition having a high drug concentration of a hydrophobic drug and capable of retaining the drug in entrapped form is described. The liposomes are comprised of high phase transition lipid and a lipopolymer, which together permit retention of a high concentration of a drug/cyclodextrin complex that achieves a high drug load that is retained even in the presence of a transmembrane osmotic gradient caused by the cyclodextrin.

Claims

1. A composition, comprising

liposomes comprised of a vesicle-forming lipid having a phase transition above about 40°

C. and of between about 1-20 mole percent of a lipid derivatized with a hydrophilic polymer;

entrapped in said liposomes, a complex comprised of a hydrophobic drug and a cyclodextrin compound, said cyclodextrin present in a concentration above about 100 mg/mL.

2. The composition of claim 1, wherein said vesicle-forming lipid is a saturated phosphatidylcholine.

3. The composition of claim 2, wherein said saturated phosphatidylcholine is distearolyphosphatidylcholine or hydrogenated soy phosphatidylcholine.

4. The composition of claim 1, wherein said liposome are further comprised of cholesterol.

5. The composition of claim 1, wherein said cyclodextrin is selected from the group consisting of methylated, phosphated, sulfated, sulfoalkyl ether, carboxymethyl, and succinylated cyclodextrins.

6. The composition of claim 5, wherein said cyclodextrin is selected from sulfobutyl ether β

-cyclodextrin or hydroxyl propyl β

-cyclodextrin.

7. The composition of claim 1, wherein said cyclodextrin is present at a concentration of greater than 200 mg/mL.

8. The composition of claim 1, wherein said cyclodextrin is present at a concentration of greater than 300 mg/mL.

9. The composition of claim 1, wherein said cyclodextrin is present at a concentration of greater than 400 mg/mL.

10. The composition of claim 1, wherein said cyclodextrin is present at a concentration of greater than 500 mg/mL.

11. The composition of claim 1, wherein said liposomes further comprise, in liposome entrapped form, a water soluble polymer, a salt, or both.

12. The composition of claim 11, wherein said water soluble polymer is selected from the group consisting of hydroxypropyl methylcellulose, polyvinyl pyrrolidone, and gelatin.

13. The composition of claim 11, wherein said salt is selected from the group consisting of sodium chloride, sodium acetate, sodium citrate, sodium salicylate, and sodium benzalkonium.

14. A liposome composition prepared according to a process comprising;

providing lipids comprised of a vesicle-forming lipid having a phase transition above about 40°

C. and of between about 1-20 mole percent of a lipid derivatized with a hydrophilic polymer,

combining the lipids with a drug-cyclodextrin solution to form liposomes having a concentration of cyclodextrin of greater than about 100 mg/mL;

processing said liposomes to obtain a desired particle size.