KR101794499B1 - Drug delivery system containing phase change material and crystalline carbon nanoparticles and method of making the same - Google Patents

Abstract

The present invention relates to a drug delivery system comprising a phase-change material and crystalline carbon nanoparticles and a method of manufacturing the same, and a drug delivery system comprising the phase-change material, the drug and the crystalline carbon nanoparticles according to the present invention, In addition to being able to regulate drug release in an appropriate amount at the appropriate time according to near-infrared irradiation during intratumoral injection, the synergistic effect of photodynamic therapy and metastatic treatment, Can be maximized.

Description

[0001] The present invention relates to a drug delivery system comprising a phase-change material and crystalline carbon nanoparticles, and a method for manufacturing the same,

The present invention relates to a drug delivery system comprising a phase-change material and crystalline carbon nanoparticles, and a method for producing the same.

To date, therapies such as immunology, chemistry, radiation, and phototherapy have been studied to treat tumors. Among them, phototherapy is a local therapy technique, which is cheap and has a great interest because it has advantages of minimizing adverse effects due to specific treatment of tumor site. Phototherapy can be categorized into two types: photodynamic therapy and photodynamic therapy, in which near-infrared light absorption is required to treat tumors. In the case of photodynamic therapy, when the photosensitizer is exposed to a particular wavelength of near infrared light, it absorbs optical energy to produce reactive oxygen species such as reactive oxygen species, which leads to the elimination of tumor cells and tissues. However, since the photosensitizer is not specific for the tumor, when the tumor patient is exposed to external near-infrared light during the photodynamic therapy, the activity of the photosensitizer spread throughout the body may cause damage to normal cells and tissues There is a limit.

Photothermal therapy is a method of killing tumor cells through a high temperature of 43 ° C or higher, and utilizes heat-absorbing properties by absorbing specific light wavelengths of photothermal materials such as carbon nanotubes, graphene, nanodiamonds, and gold nanoshells. In recent years, nanocrystals as crystalline carbon-based nanoparticles have attracted attention in the fields of medicine and biomedical engineering because they can be used as optical materials as well as excellent biocompatibility, high mechanical strength, dispersion stability, and diversification of surface functional groups. Phototherapy has a higher accumulation rate in tumor tissue due to enhanced permeability and retention effect because nanoparticles are mainly used as compared with photodynamic therapy, but there is a limit in the efficiency of tumor treatment.

Therefore, there is a need to develop materials for complementing these problems and effectively treating tumors.

 Zhi Chen et al. Synthesis and thermal properties of shape-stabilized lauric acid / activated carbon composites as phase change materials for solar energy storage, Solar Energy Materials and Solar Cells Volume 102, July 2012, Pages 131-136.

It is an object of the present invention to provide a drug carrier comprising a phase-change material, a drug, and crystalline carbon nanoparticles.

It is another object of the present invention to provide a method for producing a drug carrier comprising a phase-change material, a drug, and crystalline carbon nanoparticles.

It is still another object of the present invention to provide a drug delivery composition comprising a drug delivery vehicle.

The present invention provides a drug carrier comprising a phase-change material, a drug, and crystalline carbon nanoparticles.

The term phase change material means a latent heat material, a heat storage material, a condensation coolant or a heat control material, and is a liquid in a solid state, a solid in a liquid state, a gas in a liquid state, Is a material that accumulates a large amount of heat energy or releases stored heat energy through a kind of material conversion process (phase conversion process) which changes from a state of a state to a state of another state. In the phase transformation process, all materials change the physical arrangement of molecules, not chemical reactions such as chemical bonding. Although about 4,000 substances are classified as phase change substances, only about 200 substances are actually used.

The term "crystalline carbon nanoparticle" means a nanoparticle composed of a carbon element which is arranged in a very regular manner to exhibit crystalline and is a core material of nanotechnology, which has recently been attracting attention as an electrical and electronic material and a functional material. Examples of the crystalline carbon nanoparticles include carbon nanotubes (CNTs), carbon nanofibers, carbon nano ribbons, carbon nano onions (CNOs), carbon nanotubes (CNR), and Nanodiamond. The crystalline carbon nanoparticles are generally prepared by a method such as Arc Discharge, Catalytic Chemical Vapor Deposition (CCVD), Flame Synthesis (Flame Synthesis) are mainly used.

In the above-mentioned drug delivery vehicle, the crystalline carbon nanoparticles absorb near-infrared light when the near-infrared rays are irradiated, and the temperature of the drug carrier is elevated so that the phase-change material is phase-changed from solid to liquid and the drug carried on the drug carrier is released.

In one embodiment of the present invention, it has been confirmed that the temperature of the drug delivery vehicle (Ce6 / ND / PCM) according to the present invention increases repeatedly every time the near infrared ray is absorbed and thus the cumulative release rate of the drug, (Fig. 2). This is because the nanodiamonds as crystalline carbon nanoparticles absorb near-infrared rays, causing a phase change of lauric acid, which is a phase change material, as the temperature of the drug carrier (Ce6 / ND / PCM) It was analyzed that the acid was released as a result of cyanogen e6 release (Fig. 3).

The drug delivery vehicle may comprise 10 to 99.9% by weight of a phase change material, 0.1 to 25% by weight of a drug, and 0.1 to 75% by weight of crystalline carbon nanoparticles based on 100% by weight of the drug delivery vehicle with respect to 100% .

The phase change material may be a fatty acid type or a fatty alcohol type.

When the phase change material is a fatty acid type, specifically, it may be a mixture of lauric acid, methyl palmitate, capric acid, and erucic acid. It can be chosen from the group.

When the phase change material is a fatty alcohol type, specifically, it may be formed of tridecyl alcohol, myristyl alcohol, pentadecyl alcohol, and erucyl alcohol. It can be chosen from the group.

The phase-change material may be any phase-change material known in the art, but it is preferable that the phase-change material does not induce toxicity in the body when injected into the body through injection or the like, and the effect is exhibited by causing a phase change in the body The melting point is preferably 30 to 45 ° C. The phase change material having a melting point outside the numerical range does not exhibit the phase change in the early stage before the near infrared ray irradiation or the phase change in the present invention does not occur at the time of the near infrared ray irradiation.

The drug may be a hydrophobic drug, and the kind of the hydrophobic drug is not particularly limited, and examples thereof include anticancer agents; Antipsychotic drugs such as anxiolytics, antidepressants, neurotransmitters, and antipsychotics; A cardiovascular therapeutic agent such as a therapeutic agent for hyperlipidemia, a therapeutic agent for hypertension, a therapeutic agent for hypotension, an antithrombotic agent, a vasodilator and an arrhythmia therapeutic agent; Antiepileptics; Gastrointestinal therapeutic agents such as anti-ulcer agents; Rheumatic remedy; Sincere agent; Tuberculosis treatment; Muscle relaxants; A therapeutic agent for osteoporosis; Erectile dysfunction treatment; styptic; Hormones such as sex hormones and the like; Diabetic therapy; Antibiotic; Antifungal agents, antiviral agents; Antipyretic analgesics; Autonomic control agents; Corticosteroid; diuretic; Antidiuretic agents; painkiller; anesthetic; Antihistamines; Antigen challenge; Anemia; Anti-asthmatics; Anticonvulsants; antidote; Anti-migraine agent; Antistatic agent; Antiparkinsonian; An antitank agent; Antiplatelet agents; Jinhae expectorant; Bronchodilators; cardiac; Immunomodulators; Protein drugs, gene drugs, and mixtures thereof, and is preferably selected from the group consisting of anticancer drugs, antipsychotic drugs, hyperlipidemia drugs, hypertension drugs, epilepsy drugs, gastrointestinal drugs, rheumatic drugs, antispasmodics, tuberculosis drugs, muscle relaxants, But are not limited to, osteoporosis treatment agents, erectile dysfunction treatment agents, hemostatic agents, antiviral agents, hormone agents, antibiotics, diabetic agents, antifungal agents, antithrombotic agents, antipyretic analgesic agents and mixtures thereof.

The water-soluble drug is more particularly selected from the group consisting of chlorin e6, vinblastine, Etoposide, actinomycin D, bleomycin, methotrexate, Alkylating compounds, Alkeran, Busulfan, Cisplatinum, Cytoxan, Daunorubicin, Hydrea, Ifosfamide, ), Mithramycin, Mitomycin, Mitoxantrone, Nitrogen Mustard, Velban, Vincristine, Carboplatinum, The compounds of the present invention may be selected from the group consisting of Idarubicin, Irinotecan, Leustatin, Navelbine, Taxotere and Topotecan adriamycin, cisplatin, daunomycin, 5-fluorouracil, But it may be selected from the group consisting of cells (Paclitaxel), not limited to this.

The crystalline carbon nanoparticles may be nanodiamonds.

Terminology Nanodiamond is a kind of crystalline carbon nanoparticles, which is also called nanocrystalline diamond (Aggreagated diamond nanorod). It is a material that does not heat Fullerene, Pressure, or by applying a pressure of 2 to 20 gigapascals and a heat of 300 to 2500 캜. The Mohs hardness of nanodiamonds is 1.7 ~ 5.2% (10.17 ~ 10.52) higher than diamonds and is harder than diamonds and has not been reported to be toxic to various cell types such as neuroblasts, macrophages and PC-12 cells (Biocompatible and detectable carboxylated nanodiamond on human cell, Kuang-Kai Liu, Chia-Liang Cheng, Chia-Ching Chang and Jui-I Chao, Nanotechnology, 18 (2007) 325102).

The present invention

(I) 0.02 to 0.20 parts by weight of a phase change material, 0.005 to 0.100 parts by weight of a drug, and 0.005 to 0.100 parts by weight of crystalline carbon nanoparticles are added to 100 parts by weight of a hydrophobic solvent to prepare a non-coagulated phase;

Ii) adding and dissolving the surfactant to distilled water to produce a continuous phase; And

Iii) preparing drug carrier particles by adding the non-inversed phase of step i) to the continuous phase of step ii).

The hydrophobic solvent of step i) may be any solvent which is capable of dissolving the phase-change material and the drug and is volatile. Preferably, the hydrophobic solvent may be selected from the group consisting of dichloromethane, chloroform, hexane, But is not limited thereto.

The surfactant of step ii) may be added to prepare the drug delivery system more stably. Any surfactant that is water-soluble may be used. Preferably, sodium dodecyl sulfate (SDS), sodium lauryl sulfate sulfate, SLS, glycerin fatty acid ester, sucrose fatty acid esters, lecithin, enzyme treated lecithin, polysorbate, and sorbitan fatty acid ester ester), but is not limited thereto. Even without adding the surfactant, the drug delivery system according to the present invention can be stably produced.

The surfactant of step ii) may be added in an amount of 2 to 4 parts by weight based on 100 parts by weight of distilled water, but is not limited thereto.

The size of the drug carrier particles prepared in step iii) may range from 25 to 500 nm But is not limited thereto.

The present invention provides a drug delivery composition comprising the drug delivery system according to the present invention.

The composition for drug delivery may be for the treatment of a disease selected from the group consisting of malignant tumors and benign tumors.

The composition for drug delivery according to the present invention may be contained as an additive in a pharmaceutical composition for the treatment of diseases selected from the group consisting of malignant tumors and benign tumors and is contained in an amount of 0.001 to 10 parts by weight based on 100 parts by weight of the pharmaceutical composition. can do.

The composition for drug delivery of the present invention may be formulated in any form suitable for a pharmaceutical preparation, but most preferably it may be a formulation for parenteral administration. Specifically, it may be a sterilized aqueous solution, a non-aqueous solution, Emulsion, and freeze-drying agent. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant or the like commonly used in the art is used.

The composition for drug delivery of the present invention may be a non-aqueous solution, a suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, or the like.

The pharmaceutical dosage form of the drug delivery composition according to the present invention may be used in the form of a pharmaceutically acceptable salt thereof, and may be used alone or in combination with other pharmaceutically active compounds as well as a suitable combination. The salt is not particularly limited as long as it is pharmaceutically acceptable and includes, for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, Sulfonic acid, benzenesulfonic acid, toluenesulfonic acid, and naphthalenesulfonic acid.

The composition for drug delivery of the present invention may be administered parenterally according to the purpose, and may be administered once to several times so as to be administered in an amount of 0.1 to 500 mg and 1 to 100 mg per kg of body weight per day. The dosage for a particular patient may vary depending on the patient's body weight, age, sex, health condition, diet, time of administration, administration method, excretion rate, severity of disease, and the like.

The composition for drug delivery of the present invention can be parenterally administered to mammals such as rats, mice, livestock, and humans, and all the methods of parenteral administration can be expected. For example, intratumoral injection, intrauterine , Intracerebroventricular injection, intravenous injection, intramuscular injection, subcutaneous injection, rectal injection.

The drug delivery composition of the present invention is preferably in the form of an injection into a tumor, but is not limited thereto.

The composition for drug delivery may be injected into a tumor and then irradiated with near infrared rays to the tumor site, which is the affected part, to control drug release.

In one embodiment of the present invention, the drug delivery vehicle (Ce6 / ND / PCM) according to the present invention does not emit near-infrared rays and thus does not release the drug claworin e6 at normal temperature. During the course of the cyanogen e6 release. According to this characteristic, the drug delivery composition according to the present invention can control the release timing and release amount of the drug through the presence or absence of near-infrared irradiation on the tumor site after being injected into the tumor.

On the other hand, since the drug delivery composition of the present invention has no serious toxicity and side effects, it can be safely used for long-term treatment.

In one embodiment of the present invention, 0.01 g of lauric acid is used as a phase-change material, 0.001 g of chlorogenic e6 as a photosensitizer, and 0.01 g of nanodiamond as a crystalline carbon nanoparticle are added to dichloromethane, which is a hydrophobic solvent, And a continuous phase was prepared by dissolving 15 g of sodium dodecyl sulfate (SDS) in 500 g of distilled water. Then, nano-sized drug carrier particles (Ce6 / ND / PCM) were prepared by adding a non-emulsion phase to the continuous phase using an ultrasonic crusher.

The first feature of the present invention resides in the use of crystalline carbon nanoparticles having excellent biocompatibility as an optical material. Photothermal therapy is a method of destroying tumor cells using high heat generated by irradiation with near-infrared light to optical materials such as carbon nanotubes, graphene, nanodiamonds, and gold nanoshells. The present invention uses nanodiamonds which are crystalline carbon nanoparticles having excellent biocompatibility among optical materials to produce a drug delivery vehicle which is not toxic to normal cells and destroys tumor cells and is applied to tumor treatment.

The second feature of the present invention is that it can be manufactured by adding or substituting a drug suitable for treatment at the stage of manufacturing the drug delivery vehicle containing the phase change material and the crystalline carbon, It is in what can.

The third characteristic is that drug delivery can be controlled by including a phase transfer material in the drug delivery system. In one embodiment of the present invention, the drug carrier (Ce6 / ND / PCM) prepared according to the present invention does not emit near-infrared rays and thus does not release cyanogen e6 at room temperature (20 ° C) Chlorine e6 was released during the temperature rise (35.2 to 43.2 ° C) and cyanogen e6 was not leaked until 14 days at room temperature without near infrared irradiation. According to such characteristics, drug release timing and release amount can be controlled through the presence or absence of near-infrared irradiation. Therefore, drug-incorporated nanoparticles composed of natural polymers such as PLGA (poly (lactic-co-glycolic acid) Improvement of disadvantages of drug leakage by small amount.

The fourth feature is the ability to simultaneously perform photodynamic therapy and photodynamic therapy, thus enabling effective tumor treatment. Conventional photodynamic therapy has the disadvantage that the photosensitizer is easily expressed in the whole body and the patient is exposed to the external near-infrared light, the side effects of the general tissue necrosis and the delivery rate to the tumor are low, and photothermal therapy is put to practical use with low therapeutic efficiency There was a limit. When the drug delivery system according to the present invention includes a photosensitizer as a drug, it can simultaneously perform photodynamic therapy and photodynamic therapy, so that synergistic effects are exerted to maximize the treatment efficiency of the tumor, thereby overcoming the limitations of the existing treatment.

The fifth feature lies in direct delivery of a drug delivery vehicle containing phase-change material and crystalline carbon to the tumor via intratumoral injection. In general, intravenous injection has a problem in that the efficiency of the drug is low because the efficiency of the drug is reduced due to the hepatic first-pass effect in which the drug administered in the body is metabolized in the liver before entering the circulatory system. However, since the inner tumor of the tumor directly injects the drug into the tumor, it is possible to minimize the side effect while maximizing the efficiency of the drug. Therefore, the drug carrier prepared according to the present invention uses an intratumoral injection method. In the example, the drug delivery vehicle (Ce6 / ND / PCM) prepared according to the present invention was found to be more effective in treating cancer cells than intravenous injection (FIG. 4).

The drug carrier comprising the phase-change material, the drug and the crystalline carbon nanoparticle according to the present invention contains the drug and the crystalline carbon as the optical material in the heat-sensitive phase-change material. Therefore, And the synergistic effects of photodynamic therapy and photodynamic therapy can maximize the effect of tumor treatment.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph showing a particle surface appearance of a drug carrier (Ce6 / ND / PCM), (B) an inner appearance, (C) a particle size distribution, and (D) surface charge.
FIG. 2 is a graph showing the cumulative drug release rate of a drug delivery vehicle (Ce6 / ND / PCM) according to temperature change upon irradiation with near infrared rays.
FIG. 3 is a schematic diagram showing a drug release process according to a temperature change when a near-infrared ray irradiation is performed on a drug delivery vehicle (Ce6 / ND / PCM).
4 is a graph showing the drug release rate at room temperature (20 ° C) without irradiation of near infrared rays to the drug delivery vehicle (Ce6 / ND / PCM).
FIG. 5 is a graph showing the results of a comparison between a sample after washing with a drug carrier (Ce6 / ND / PCM) in a cancer cell culture medium and a sample with a near infrared ray irradiated before the drug carrier (Ce6 / ND / PCM) (A) and (B) images of the cytotoxicity (scale bar: 200 μm).
FIG. 6 is a graph showing the amount of drug released from nude mice injected into a tumor with a drug delivery vehicle (Ce6 / ND / PCM) according to irradiation time of near-infrared rays.
FIG. 7 is a graph showing changes in tumor size with time in a nude mouse irradiated with near-infrared rays after injecting a drug delivery vehicle (Ce6 / ND / PCM) into a tumor.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

& Lt; Example 1 & gt; A drug delivery system comprising a phase change material and crystalline carbon nanoparticles

0.01 g of Lauric Acid, 0.001 g of chlorin e6 and 0.01 g of nano diamond were added to 10 g of dichloromethane (DCM) to prepare a non-drawn shape. Then, 15 g of sodium dodecyl sulfate (SDS) was dissolved in 500 g of distilled water to prepare a continuous phase. Nano-sized drug carrier particles carrying the drug claworin e6 were prepared by adding a non-emulsion phase to the continuous phase using an ultrasonic shredder (Ultrasonication, Sonics and Materials Inc., USA), dialyzed and lyophilized. Zeta potential and particle size of the prepared drug delivery system (Ce6 / ND / PCM) were confirmed by Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM).

As a result, the surface and inner appearance of the drug delivery vehicle (Ce6 / ND / PCM) was as shown in Figs. 1A and 1B, the zeta potential was -31.3 ± 5.6 mV, and the particle size was 101.9 ± 31.1 nm (Fig. 1) .

& Lt; Example 2 & gt; Temperature change and drug release behavior of drug carriers according to near-infrared irradiation

0.1 mg of the drug carrier (Ce6 / ND / PCM) prepared in Example 1 was dispersed in 0.1 g of distilled water. After 6 minutes of no treatment, no treatment was carried out. Then, using a laser diode (InGaAs diode, NDLUX, Korea) The process of irradiating the near infrared ray (NIR) was repeated three times to confirm the temperature change of the drug delivery system (Ce6 / ND / PCM) and the release behavior of corynefin e6 by noncontinuous NIR irradiation.

As a result, every time the drug delivery system (Ce6 / ND / PCM) absorbs near-infrared rays irradiated discontinuously, the temperature is repeatedly increased to 41.8 ± 1.2 ° C and the cumulative release rate of the drug, croolin e6, (Fig. 2). This is because the nano-diamonds as crystalline carbon nano-particles absorb near infrared rays and phase change of lauric acid occurs as the temperature of the drug carrier (Ce6 / ND / PCM) rises and lauric acid is recorded, (Fig. 3).

In the case of the drug delivery system Ce6 / ND / PCM, no cyanine e6 release occurs at room temperature (20 ° C) without irradiation with near infrared rays. While the temperature is raised after irradiation with near infrared rays (35.2 to 43.2 ° C ) Chlorine e6 was released. In the case of the drug delivery vehicle (Ce6 / ND / PCM), cyanine e6 did not leak up to 14 days at room temperature without near infrared irradiation (FIG. 4).

According to such characteristics, the drug delivery system (Ce6 / ND / PCM) according to the present invention can control the drug release timing and release amount through the irradiation with near infrared rays, The drug delivery system (Ce6 / ND / PCM) according to the present invention releases the drug in an appropriate amount at the appropriate time in the affected part The treatment effect can be maximized.

<Example 3> Cytotoxicity test of drug delivery vehicle

1 mg of the drug delivery vehicle (Ce6 / ND / PCM) prepared in Example 1 was administered to KB cells derived from epidermal carcinoma tissues in order to compare the therapeutic efficiency in intravenous injection or intratumoral injection of the drug delivery vehicle (Ce6 / ND / PCM) (1 x 10 ⁴ ) culture samples were each treated for 24 hours. Subsequently, after the culture medium in the culture medium sample treated with the drug carrier (Ce6 / ND / PCM) was removed as a model for intravenous injection, a sample washed with PBS (phosphate buffered saline) As a model for indoor use, a sample was irradiated with near infrared rays for 4 minutes without washing the culture medium in the sample with the drug carrier (Ce6 / ND / PCM), and the cell counting kit -8, Dojindo Co. Ltd., Japan) was used to measure the amount of cells after irradiation with near infrared rays, and the amount of total cells was used to confirm the cytotoxicity as a percentage.

As a result, after washing of the drug carrier (Ce6 / ND / PCM) in the culture medium, the cell viability was 48.8%, and the drug carrier (Ce6 / ND / PCM) Was 24.8% in the cell viability (Fig. 5). Therefore, it was confirmed that the drug delivery system (Ce6 / ND / PCM) was more effective in treating cancer cells than intravenous injection after intratumoral injection.

&Lt; Example 4 > Drug release test of drug carrier in tumor

The drug carrier (Ce6 / ND / PCM) prepared in Example 1 was administered to nude mice bearing KB cell xenografted tumors at a dose of 24 mg / kg (drug carrier (Ce6 / ND / PCM) / nude mouse weight) Respectively. Thereafter, near infrared rays were irradiated for 1 minute, 2 minutes, 4 minutes and 6 minutes to confirm the amount of corynefin e6 emission according to the near infrared ray irradiation time. The release and diffusion of coryne-e6 in the nude mouse body was confirmed using an image station (Image Station 4000 MM, Kodak, USA).

As a result, the drug delivery system (Ce6 / ND / PCM) was injected into the tumor, and it was confirmed that the corydalene e6 diffused throughout the nude mice as irradiation time elapsed during near infrared irradiation (FIG. 6).

Example 5 Tumor Size Reduction Effect of Drug Delivery System

The nanoparticles (ND / PCM) (control group) prepared in the same manner as in Example 1 except for the drug carrier (Ce6 / ND / PCM) prepared in Example 1 and the drug Cloorin e6 (Ce6 / ND / PCM) or nanoparticle (ND / PCM) / nude mouse weight) was injected intratumorally into nude mice bearing the tumor. The tumor size was measured according to the calculation method of volume (cm ³ ) = 0.523 × length (cm) × width ² (cm ² ) according to the duration of tumor treatment (MH El-Dakdouki et al. ACS Appl. Mater: Interfaces 2014, 6, 697.).

As a result, the initial tumor size of the nude mouse was 33.8 ± 4.8 mm ^3, but the tumor size of the nude mice injected with the drug carrier (Ce6 / ND / PCM) according to the present invention was significantly decreased with time, And 10.4 +/- 3.4 mm &lt; ³ &gt; at day 12 post-injection (Fig. 7). However, the tumor size of nude mice injected with tumor-naïve nanoparticles (ND / PCM) without control was 660.7 ± 38.8 mm ³ on the 12th day after injection into the tumor, indicating that the tumor treatment effect was insignificant. Thus, it has been confirmed that the drug delivery system (Ce6 / ND / PCM) according to the present invention has an effect of reducing tumor size by releasing coryne e6 and killing cancer cells by near infrared irradiation.

Claims (11)

1. A drug delivery system comprising a phase change material, a drug and crystalline carbon nanoparticles,
In the drug delivery system, the crystalline carbon nanoparticles absorb near-infrared light when irradiated with near-infrared rays, and the temperature of the drug carrier is increased. As a result, the phase change material is phase-changed from solid to liquid,
The phase change material is selected from the group consisting of Fatty Acid and Fatty alcohol having a melting point of 30 to 45 캜,
The drug may be selected from the group consisting of chlorin e6, vinblastine, etoposide, actinomycin D, bleomycin, methotrexate, alkylating compounds , Alkeran, Busulfan, Cisplatinum, Cytoxan, Daunorubicin, Hydrea, Ifosfamide, Mithramycin, ), Mitomycin, Mitoxantrone, Nitrogen Mustard, Velban, Vincristine, Carboplatinum, Idarubicin, Irinotecan, Irinotecan, Leustatin, Navelbine, Taxotere and Topotecan adriamycin, cisplatin, daunomycin, 5- A group consisting of 5-fluorouracil and paclitaxel / RTI &gt;
Wherein the crystalline carbon nanoparticles are nanodiamonds.
The drug carrier according to claim 1, wherein the drug delivery vehicle comprises 5 to 15 parts by weight of a phase change material and 5 to 10 parts by weight of crystalline carbon nanoparticles based on 1 part by weight of the drug.
The method according to claim 1, wherein the fatty acid is selected from the group consisting of Lauric Acid, Methyl Palmitate, Capric Acid and Erucic Acid. &Lt; / RTI &gt;
The method of claim 1, wherein the fatty alcohol is selected from the group consisting of tridecyl alcohol, myristyl alcohol, pentadecyl alcohol, and erucyl alcohol. &Lt; / RTI &gt;
(I) 0.02 to 0.20 parts by weight of a phase change material, 0.005 to 0.100 parts by weight of a drug, and 0.005 to 0.100 parts by weight of crystalline carbon nanoparticles are added to 100 parts by weight of a hydrophobic solvent to prepare a non-coagulated phase;
Ii) adding distilled water to the distilled water and dissolving the surfactant to produce a continuous phase; And
Iii) preparing a drug carrier particle by adding the non-inversed phase of step i) to the continuous phase of step ii)
In the drug delivery system, the crystalline carbon nanoparticles absorb near-infrared light when irradiated with near-infrared rays, and the temperature of the drug carrier is increased. As a result, the phase change material is phase-changed from solid to liquid,
The phase change material is selected from the group consisting of Fatty Acid and Fatty alcohol having a melting point of 30 to 45 캜,
The drug may be selected from the group consisting of chlorin e6, vinblastine, etoposide, actinomycin D, bleomycin, methotrexate, alkylating compounds , Alkeran, Busulfan, Cisplatinum, Cytoxan, Daunorubicin, Hydrea, Ifosfamide, Mithramycin, ), Mitomycin, Mitoxantrone, Nitrogen Mustard, Velban, Vincristine, Carboplatinum, Idarubicin, Irinotecan, Irinotecan, Leustatin, Navelbine, Taxotere and Topotecan adriamycin, cisplatin, daunomycin, 5- A group consisting of 5-fluorouracil and paclitaxel / RTI &gt;
The crystalline carbon nanoparticles are nanodiamonds,
The hydrophobic solvent is selected from the group consisting of dichloromethane, chloroform, hexane, acetone,
Wherein the surfactant is a water-soluble surfactant.
6. The method of claim 5, wherein the surfactant of step (ii) is added in an amount of 2 to 4 parts by weight based on 100 parts by weight of distilled water.
6. The method of claim 5, wherein the size of the drug carrier particles prepared in step (iii) is 25 to 500 nm.
A drug delivery composition comprising the drug delivery system of claim 1.
9. The drug delivery composition according to claim 8, wherein the composition for drug delivery is for the treatment of a disease selected from the group consisting of malignant tumors and benign tumors.
9. The composition for drug delivery according to claim 8, wherein the composition for drug delivery is in the form of an injection into a tumor.
[Claim 9] The composition for drug delivery according to claim 8, wherein the drug delivery composition is injected into a tumor and then the near-infrared rays are irradiated to the lesion to control drug release.

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