KR-20260063236-A - Ligand-attached Liposome Structure Comprising Resveratrol Encapsulated Therein, Method for Preparing Same and Composition for Improving Fatty Liver Disease

KR20260063236AKR 20260063236 AKR20260063236 AKR 20260063236AKR-20260063236-A

Abstract

The present invention relates to a ligand-attached liposome structure containing resveratrol, a method for manufacturing the same, and a composition for improving fatty liver containing the same. In the present invention, by encapsulating resveratrol in liposomes and introducing sitosterol glucoside, a food-derived substance, into the lipid membrane, a drug delivery system capable of target delivery via a glucose ligand capable of reacting with receptors in organs, which has excellent stability and cell permeability without synthetic materials, can be produced. Accordingly, by using a drug delivery system in which resveratrol is encapsulated in ligand-attached liposomes according to the present invention, non-alcoholic fatty liver disease can be improved by effectively inhibiting fat accumulation in liver cells.

Inventors

이현규
백유진

Assignees

한양대학교 산학협력단

Dates

Publication Date: 20260507
Application Date: 20241030

Claims (14)

Resveratrol-encapsulated liposomes, and Sitosterol glucoside inserted into the lipid membrane of the above liposome A ligand-attached liposome structure comprising
In Article 1, A ligand-attached liposome structure in which the sitosterol structure of the above-mentioned sitosterol glucoside is embedded in the lipid membrane of the liposome, and the glucose structure protrudes outside the lipid membrane of the liposome and acts as a ligand.
In Article 1, A ligand-attached liposome structure in which the lipid membrane of the above liposome comprises a phospholipid bilayer and cholesterol.
In Paragraph 3, A ligand-attached liposome structure comprising one or more types of phospholipids selected from the group consisting of neutral lipids, anionic phospholipids, and cationic phospholipids.
In Paragraph 3, A ligand-attached liposome structure having a weight ratio of phospholipid to cholesterol of 0.5:1 to 20:1.
In Paragraph 3, A ligand-attached liposome structure having a weight ratio of the above phospholipid and sitosterol glucoside of 1:0.1 to 1:2.
In Article 1, A ligand-attached liposome structure having an average particle size of 50 to 150 nm.
In Article 1, A ligand-attached liposome structure having a polydispersity index (PDI) of 0.1 to 0.4 of the above-mentioned ligand-attached liposome structure particles.
A step of forming a mixture by mixing phospholipids, cholesterol, sitosterol glucoside, and resveratrol; A step of forming a thin film by removing the solvent from the above mixture; and A step of hydrating the above thin film to form a structure in which a phospholipid bilayer and cholesterol form a lipid membrane to form liposomes, resveratrol is captured in the liposomes, and sitosterol glucoside is inserted into the lipid membrane. A method for manufacturing a ligand-attached liposome structure comprising
In Article 9, A method for preparing a ligand-attached liposome structure, wherein the concentration of resveratrol in the above mixture is 0.05 to 5 mg/mL.
In Article 9, A method for manufacturing a ligand-attached liposome structure, wherein in the thin film formation step above, the removal of the solvent is performed by evaporating the solvent through vaporization or drying.
In Article 9, A method for manufacturing a ligand-attached liposome structure, comprising the step of hydrating the thin film and then performing ultrasonic treatment.
A food composition comprising a ligand-attached liposome structure according to any one of claims 1 to 8.
In Article 13, The above food composition is a food composition for improving non-alcoholic fatty liver.

Description

Ligand-attached liposome structure encapsulating resveratrol, method for preparing the same, and composition for improving fatty liver disease comprising the same The present invention relates to a ligand-attached liposome structure encapsulating resveratrol, a method for manufacturing the same, and a composition for improving fatty liver containing the same. More specifically, by encapsulating resveratrol in a liposome and introducing sitosterol glucoside, a food-derived ligand, into a lipid membrane, the invention relates to a liposome structure capable of target delivery by a ligand that has excellent stability and cell permeability and can react with receptors in organs, a method for manufacturing the same, and a composition for improving fatty liver containing the same. Non-alcoholic fatty liver disease (NAFLD) is a condition in which triglycerides accumulate in 5 to 10 percent of liver cells and is primarily caused by obesity and the excessive accumulation of lipids in the liver. NAFLD is a chronic disease affecting approximately one-third of the populations in Asia and the West, and if left untreated, it can progress to steatohepatitis, cirrhosis, and even liver cancer. Currently, treatment methods for NAFLD include weight loss, lifestyle changes, and medication; however, as side effects have been reported with medications, there is a need to develop drugs that can effectively improve NAFLD without side effects. Regarding treatments for non-alcoholic fatty liver disease, resveratrol is a type of polyphenol compound found in plants that is known to have excellent antioxidant activity and is effective in preventing obesity, inhibiting cancer, and improving cardiovascular disease, and is being proposed as a candidate for the treatment of non-alcoholic fatty liver disease. However, resveratrol has limitations in that it is difficult to exert its efficacy in the body due to its low solubility, stability, and cell permeability. In particular, when resveratrol is administered orally, there is a problem that it is eliminated by binding to glucuronic acid and sulfates in liver and intestinal epithelial cells. Generally, a representative technology for overcoming the disadvantages of drugs with low solubility and stability, such as resveratrol, is the use of drug delivery systems such as micelles and liposomes. For example, Korean Registered Patent Publication No. 10-1334420 describes a technology that uses a polymer compound to form micelles and encapsulates a drug inside them to be used as a drug delivery vehicle, and Korean Registered Patent Publication No. 10-1612194 describes a drug delivery composition containing a liposome encapsulated with a drug-containing nanoparticle, and describes a drug delivery vehicle in which nanoparticles containing paclitaxel bound to albumin are encapsulated in a liposome. However, for the improvement of non-alcoholic fatty liver disease, it is important to increase hepatocyte transport rates as well as improve solubility and stability; yet, conventional liposomes lack these targeted activities, which limits their ability to enhance the disease's improvement. Furthermore, while technologies are being developed to introduce substances that confer targeted activity onto liposomes, most of these technologies utilize synthetic materials, which limits their application in the food and pharmaceutical industries. Therefore, there is a need to develop a drug delivery system that can effectively improve non-alcoholic fatty liver disease by increasing the solubility and stability of resveratrol while enabling hepatocyte targeting. Figure 1 schematically shows the structure of a ligand-attached liposome structure according to one embodiment of the present invention. Figure 2 shows the particle size, polydispersity index (PDI), and zeta potential measurement results of drug-capturing liposomes produced in one embodiment of the present invention. Figure 3 shows the results of measuring the drug capture efficiency of liposomes according to the ratio of phosphatidylcholine and cholesterol in drug capture liposomes produced in one embodiment of the present invention. Figure 4 shows the results of measuring the lipid content of cells after liposome treatment according to the ratio of phosphatidylcholine and cholesterol in drug-capturing liposomes produced in one embodiment of the present invention. Figure 5 shows the particle size, polydispersity index, and zeta potential measurements of liposome structures according to the ratio of phosphatidylcholine and Sito-G in a ligand-attached liposome structure fabricated in one embodiment of the present invention. Figure 6 shows the results of measuring the drug capture efficiency of liposome structures according to the ratio of phosphatidylcholine and Sito-G in ligand-attached liposome structures fabricated in one embodiment of the present invention. Figure 7 shows the results of measuring the Caco-2 cell permeability activity of liposomes accordin