Synthetic liposomes for enhanced uptake and delivery

• US 5,512,295 A
• Filed: 11/10/1994
• Issued: 04/30/1996
• Est. Priority Date: 11/10/1994
• Status: Expired due to Fees

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Kornberg, Arthur, Castuma, Celina
• Primary Examiner(s): KISHORE, GOLLAMUDI S
• Application Number:
  US08/337,632
• Time in Patent Office: 537 Days
• Field of Search: 424/450, 428/402.2, 436/829, 264/4.1, 264/4.3
• US Class Current: 424/450
• CPC Class Codes: A61K 47/6911 the form being a liposome
• 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: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

Liposomes are prepared comprising a polyhydroxybutyrate calcium polyphosphate complex which provides for uptake of a desired component, particularly nucleotides and nucleic acids. The charged species may be introduced into the lumen of a liposome by incubating liposomes with a solution of the component of interest for sufficient time to provide for introduction of the component into the lumen of the liposome, followed by washing at diminished temperatures. The resulting liposomes may then be used as vehicles for delivery of the lumen component.

Claims

1. A liposome comprising a poly-β

-hydroxybutyrate calcium polyphosphate complex in the membrane of lamellar forming phospholipids.

2. A liposome according to claim 1, wherein said phospholipids are at least 75 mole % of total lipids present in said liposome.

3. A liposome according to claim 2, wherein said phospholipids are from the membrane of a unicellular microorganism or synthetic phospholipids.

4. A liposome according to claim 3, wherein said poly-β

-hydroxybutyrate is obtained from a unicellular microorganism.

5. A liposome according to claim 1, wherein the mole ratio of lipid to poly-β

-hydroxybutyrate is in the range of about 10-60;

1.

6. A liposome according to claim 1, comprising a nucleotide at a concentration of at least about 0.1 mM in the lumen of said liposome.

7. A liposome according to claim 1, comprising a nucleic acid at a concentration of at least about 0.1 mM in the lumen of said liposome.

8. A liposome according to claim 1 comprising a fusogen bound to the surface of said liposome.

9. A method for making a liposome according to claim 1 comprising:

sonicating an intimate mixture of lipids comprising at least about 80 mole % phospholipids and a poly-β

-hydroxybutyrate calcium polyphosphate complex in an aqueous medium for sufficient time for liposomes to form.

10. A method according to claim 9, comprising the additional step of extruding said liposomes through a membrane having pores of from about 0.1 to 1μ

.

11. A method of delivering a compound to a site of a host, said method comprising:

administering a liposome according to claim 1 comprising said compound in the lumen of said liposome to said site or to the blood stream of said host upstream from said host.

12. A method according to claim 11, wherein said site comprises a member of a specific binding pair and said liposome has associated with the membrane of said liposome the complementary member of said specific binding pair.