Acid stable liposomal compositions and methods for producing the same

Patent metadata

Field	Value
Publication number	US-10272041-B2
Application number	US-201414211957-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Apr 30, 2019
Grant date	Apr 30, 2019

Abstract

The present invention relates to a liposomal formulation for oral delivery of a bioactive agent that considers pH stability and oxidative stability of a bioactive ingredient. These lipid formulations are superior to conventional liposomes due to their stability, thereby circumventing the need for intra-venous delivery of bioactive agents. In one embodiment, the methods and compositions of the present invention relate to the oral delivery of insulin or a prodrug thereof.

First claim

What is claimed:

1. A liposomal formulation comprising 1,2-di-O-hexadecyl-sn-glycero-3-phosphatidylcholine and 1,2-di-O-phytanyl-sn-glycero-3-phosphatidylethanolamine, wherein the 1,2-di-O-hexadecyl-sn-glycero-3-phosphatidylcholine and 1,2-di-O-phytanyl-sn-glycero-3-phosphatidylethanolamine form uniformly sized particles; wherein the molar ratio of 1,2-di-O-hexadecyl-sn-glycero-3-phosphatidylcholine: 1,2-di-O-phytanyl-sn-glycero-3-phosphatidylethanolamine of the formulation is in the range of 2:1 to 2:3; and wherein the liposomal formulation is stable at a pH of at least 1.

2. The liposomal formulation of claim 1 , wherein the particles comprise: liposomes, nanoliposomes, niosomes, microspheres, nanospheres, nanoparticles, micelles or archaeosomes.

3. The liposomal formulation of claim 2 , wherein the uniformly-sized particles encapsulate a bioactive agent.

4. The liposomal formulation of claim 3 , wherein the bioactive agent is insulin or a pro-drug thereof.

5. The liposomal formulation of claim 3 , having a molar ratio of: 1,2-di-O-hexadecyl-sn-glycero-3-phosphatidylcholine, 1,2-di-O-phytanyl-sn-glycero-3-phosphatidylethanolamine and bioactive agent of 6:3:1.

6. The liposomal formulation of claim 3 , wherein the bioactive agent is docosahexanoic acid (DHA).

7. The liposomal formulation of claim 3 , wherein the uniformly-sized particles further comprise a PEGylated lipid.

8. The liposomal formulation of claim 7 , wherein the uniformly-sized particles comprise up to 20 molar percent of the PEGylated lipid.

9. The liposomal formulation of claim 7 , wherein the PEGylated lipid is 1,2-di-O-phytanyl-sn-glycero-3-phosphatidylethanolamine-PEG2000.

10. The liposomal formulation of claim 7 , wherein the PEGylated lipid is 1,2 distearoyl-phosphatidylethanolamine-PEG2000.

11. The liposomal formulation of claim 7 , wherein the formulation has a molar ratio of 1,2-di-O-hexadecyl-sn-glycero-3-phosphatidylcholine: 1,2-di-O-phytanyl-sn-glycero-3-phosphatidylethanolamine: PEGylated lipid of 5:3:2.

12. The liposomal formulation of claim 7 , wherein the formulation has a molar ratio of: 1,2-di-O-hexadecyl-sn-glycero-3-phosphatidylcholine: 1,2-di-O-phytanyl-sn-glycero-3-phosphatidylethanolamine: PEGylated lipid of 4.5:4.0:1.5.

Assignees

• Penn State Res Found

Inventors

• Kester Mark
• El-Bayoumy Karam
• Skibinski Christine
• Das Arunangshu

Classifications

• A61K9/127 Primary

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

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• A61K9/1278

  Post-loading, e.g. by ion or pH gradient · CPC title

• A61K38/28

  Insulins · CPC title

• A61K31/202

  having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557) · CPC title