pH sensitive fluorescent polydiacetylene liposome and delivery vehicle comprising same

Patent metadata

Field	Value
Publication number	US-9675712-B2
Application number	US-201314418341-A
Country	US
Kind code	B2
Filing date	Jul 2, 2013
Priority date	Jul 4, 2012
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

The present invention relates to a drug delivery vehicle comprising a polydiacetylene liposome, wherein a lipid bilayer is formed by a mixture of 10,12-pentacosadiynoic acid (PCDA), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and N-palmitoyl homocysteine (PHC), and a drug to be delivered is encapsulated in an isolated inner space of a polydiacetylene liposome. The PDA liposome drug delivery vehicle of the present invention comprises a lipid layer formed by mixing different phospholipids, excluding polydiacetylene, so as to be stable, and thus any leakage problems of an encapsulated drug are eliminated. In addition, since the liposome is sensitive to a pH, the shape and size thereof can be readily changed through the formation of a liposome-liposome conjugate by the improved sensitivity of the drug delivery vehicle under a specific acidic requirement, thereby enabling selective drug release, and thus can be applied as a drug delivery vehicle for various target materials. Additionally, the release of a drug can be controlled by controlling a pH requirement of the surroundings, and a drug release process can be monitored in real time through the fluorescence expressed by the stimulation to the surroundings.

First claim

What is claimed is:

1. A polydiacetylene liposome having an inner space isolated from a medium by a lipid layer membrane, wherein the lipid layer comprises 10,12-pentacosadiynoic acid (PCDA), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and N-palmitoyl homocysteine (PHC), wherein a molar ratio of the PCDA, DOPE and PHC is 6:3:1.

2. The polydiacetylene liposome of claim 1 , wherein the polydiacetylene liposome increases in diameter with decreasing pH.

3. The polydiacetylene liposome of claim 1 , wherein the polydiacetylene liposome fluoresces inherently in response to an environmental stimulus comprising a change in pH, to produce a real-time monitorable fluorescence.

4. A drug delivery vehicle comprising a polydiacetylene liposome having an inner space isolated from a medium by a lipid layer membrane, wherein the lipid layer comprises 10,12-pentacosadiynoic acid (PCDA), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and N-palmitoyl homocysteine (PHC), and the drug to be delivered is encapsulated in the isolated inner space of the polydiacetylene liposome, wherein a molar ratio of the PCDA, DOPE and PHC is 6:3:1.

5. The drug delivery vehicle of claim 4 , wherein the liposome increases in diameter with decreasing pH.

6. The drug delivery vehicle of claim 5 , wherein the drug in the liposome is released when the polydiacetylene liposome is fused with the adjacent polydiacetylene liposome, and during the drug release, the polydiacetylene liposome itself fluoresces inherently by environmental stimulus, and the fluorescence can be monitored in real -time.

7. The drug delivery vehicle of claim 4 , wherein the drug is an anti-biotic drug or an anti-cancer drug.

8. A drug delivery method using the drug delivery vehicle of claim 4 , wherein the drug delivery vehicle controls a drug release time and a drug release amount by the following steps:
(a) controlling the drug release time by controlling pH of the medium within a range of pH 3 to pH 7 with respect to the drug delivery vehicle;
(b) expressing inherent fluorescence of the liposome according to a pH change which is an external stimulus while releasing the drug by controlling the drug release time at same time; and
(c) confirming and monitoring the drug release and the drug release amount in real-time by measuring the fluorescence intensity of the liposome.

Assignees

• Univ Korea Res & Bus Found

Inventors

• Sim Sang Jun
• Won Sang Ho
• Lee Jong Uk

Classifications

• A61K9/1271

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

• A61K9/1272

  comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) · CPC title

• A61K49/0084 Primary

  liposome, i.e. bilayered vesicular structure · CPC title

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K49/0019

  characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules · CPC title