KR-20260063235-A - Liposome-micelle Complex Having Drug Encapsulated Therein, Method for Preparing Same and Composition for Oral Administration Comprising Same

KR20260063235AKR 20260063235 AKR20260063235 AKR 20260063235AKR-20260063235-A

Abstract

The present invention relates to a liposome-micelle complex encapsulating a drug, a method for manufacturing the same, and a composition for oral administration containing the same. In the present invention, a liposome-micelle complex in the form of a particle with excellent stability can be produced by incorporating micelles loaded with a drug into the hydrophilic portion of a liposome, and the use of said liposome-micelle complex can improve the solubility, pH stability, and bioavailability of the captured drug. Accordingly, the liposome-micelle complex containing a drug according to the present invention can be effectively used in oral formulations due to its excellent digestive stability and bioavailability.

Inventors

이현규
백유진

Assignees

한양대학교 산학협력단

Dates

Publication Date: 20260507
Application Date: 20241030

Claims (15)

Liposomes in the form of particles comprising a phospholipid bilayer and a water-soluble space surrounded by said phospholipid bilayer; and A micelle located in the aqueous space of the above liposome, containing a drug inside a shell made of a surfactant. A drug-encapsulated liposome-micelle complex comprising
In Article 1, A drug-encapsulated liposome-micelle complex in which the above surfactant comprises glycyrrhizic acid.
In Article 1, A drug-encapsulated liposome-micelle complex comprising 50 to 200 parts by weight of the above surfactant per 1 part by weight of the drug.
In Article 1, A liposome-micelle complex encapsulating a drug, wherein the drug is one or more water-insoluble drugs selected from the group consisting of resveratrol, cisplatin, paclitaxel, and docetaxel.
In Article 1, A drug-encapsulated liposome-micelle complex comprising one or more types of phospholipids selected from the group consisting of neutral lipids, anionic phospholipids, and cationic phospholipids.
In Article 1, A drug-encapsulated liposome-micelle complex comprising 5 to 50 parts by weight of the above phospholipid per 1 part by weight of the drug loaded within the micelle.
In Article 1, A drug-encapsulated liposome-micelle complex in which the above-mentioned phospholipid bilayer further contains cholesterol.
In Article 7, A drug-encapsulated liposome-micelle complex having a weight ratio of phospholipid to cholesterol of 2:1 to 20:1.
In Article 1, A drug-encapsulated liposome-micelle complex having an average particle size of 50 to 150 nm.
A step of forming a thin film with a solution containing a surfactant and a drug, and hydrating the formed thin film to produce micelles loaded with the drug; and A step of forming a thin film with a lipid solution containing phospholipids, and hydrating the formed lipid thin film with an aqueous phase containing micelles loaded with the drug and distilled water to produce a liposome-micelle complex in which micelles loaded with the drug are incorporated into the aqueous space inside the liposome. A method for preparing a drug-encapsulated liposome-micelle complex comprising
In Article 10, A method for preparing a drug-encapsulated liposome-micelle complex, wherein, in the micelle preparation step above, the concentration of the surfactant in the solution is 5 to 100 mg/mL.
In Article 10, A method for preparing a drug-encapsulated liposome-micelle complex, wherein, in the micelle preparation step above, the concentration of the drug in the solution is 0.05 to 5 mg/mL.
In Article 10, A method for preparing a drug-encapsulated liposome-micelle complex, wherein, in the step of preparing the liposome-micelle complex above, the concentration of phospholipids in the lipid solution is 1 to 20 mg/mL.
In Article 10, A method for preparing a drug-encapsulated liposome-micelle complex in which the above lipid solution further contains cholesterol.
A composition for oral administration comprising a liposome-micelle complex encapsulating a drug according to any one of claims 1 to 9.

Description

Liposome-micelle complex having drug encapsulated therein, method for preparing the same, and composition for oral administration comprising the same The present invention relates to a liposome-micelle complex containing a drug, a method for manufacturing the same, and a composition for oral administration containing the same. More specifically, the invention relates to a liposome-micelle complex in which micelles containing a drug are incorporated into the hydrophilic portion of a liposome to improve the solubility, stability, and bioavailability of the drug, a method for manufacturing the same, and a composition for oral administration containing the same. Water-insoluble drugs refer to drugs that do not dissolve well in water due to the inclusion of hydrophobic parts in their compound structure. Their use is limited due to this poor solubility, and there have been reports of cases where the use of additional substances is restricted due to the toxicity of the added substances when additional substances are added to resolve the poor solubility. For example, resveratrol is a type of polyphenol that has the advantage of excellent antioxidant activity, but as a water-insoluble drug, it has limitations in terms of solubility, stability, and bioavailability. To improve the stability of such water-insoluble drugs, various drug delivery systems have been developed, and representative of these systems is the technology of encapsulating drugs within micelles or liposomes. Micelles refer to nanoscale particles containing a shell composed of a surfactant. When drugs are encapsulated within micelles, they offer the advantage of smaller particle size and improved drug solubility and cellular permeability. For example, Korean Registered Patent Publication No. 10-1334420 describes a technology utilizing micelles formed from polymer compounds and encapsulated within them to serve as drug delivery systems. However, micelles present a problem regarding reduced stability in the intestinal environment upon ingestion, as structural transformation can occur as pH increases depending on the surfactant material. Meanwhile, a liposome refers to a spherical or elliptical particle-shaped structure formed by a phospholipid bilayer; because it possesses characteristics similar to a cell membrane, utilizing it offers the advantage of facilitating intracellular absorption. As an example, Korean Registered Patent Publication No. 10-1612194 relates to a drug delivery composition comprising liposomes encapsulating drug-containing nanoparticles, describing a drug delivery system in which nanoparticles containing albumin-conjugated paclitaxel are encapsulated within liposomes. However, liposomes present a problem in that the stability of the lipid bilayer decreases in low pH environments, leading to their degradation in the stomach upon ingestion. As such, while using micelles or liposomes as drug delivery vehicles can increase drug solubility, there was a limitation in that the drug delivery effect was reduced when used in oral formulations that must pass through digestive environments of various pH levels due to instability under specific pH conditions. Accordingly, there is a need to develop drug delivery systems that can improve the solubility and bioavailability of water-insoluble drugs and maintain their structure under various pH conditions, making them effective for use in oral formulations. FIGS. 1a, 1b, and 1c schematically show the structures of a drug-carrying liposome-micelle complex (a), a drug-carrying micelle (b), and a drug-carrying liposome (c), respectively, according to one embodiment of the present invention. Figure 2 shows the particle size, polydispersity index (PDI), and zeta potential measurement results of drug-carrying micelles produced in one embodiment of the present invention. Figure 3 shows the measurement results of the capture efficiency of drug-carrying micelles produced in one embodiment of the present invention. Figure 4 shows the results of measuring the solubility of a drug (resveratrol) in a drug-carrying micelle produced in one embodiment of the present invention. FIGS. 5a, 5b, and 5c each show transmission electron microscope images of a drug-carrying micelle (a), a drug-carrying liposome (b), and a drug-carrying liposome-micelle complex (c) fabricated in one embodiment of the present invention. Figure 6 shows the results of measuring the drug solubility of a liposome-micelle complex according to one embodiment of the present invention. Figure 7 shows the pH stability measurement results of a liposome-micelle complex according to one embodiment of the present invention. Figure 8 shows the results of measuring the bioavailability of a liposome-micelle complex according to one embodiment of the present invention. Figure 9 shows the results of measuring the change in particle size before and after digestion of a liposome-micelle complex according to one embodiment of the present invention. Figure 10 sho