KR101633137B1 - Liposommal microstructure for drug delivery and Method for preparing the same - Google Patents

Abstract

The present invention relates to a liposome-microstructure comprising a liposome containing a skeletal material-carrying drug, and a method for producing the same. The present invention can deliver a water-soluble or liposoluble drug to a liposome and deliver the drug through the skin to the body, which has not been readily absorbed. According to the present invention, a microstructure having a simple structure can be provided by using a liposome capable of drug delivery function as a skeleton of a microstructure.
The liposome-microstructures of the present invention can selectively and locally deliver drugs effectively and stably to desired sites such as cancer, muscle, and cell using the drug transfer characteristics of liposomes.

Description

Liposome-microstructures for drug delivery and methods for preparing the same

 The present invention relates to a liposome-microstructure for drug delivery and a method for preparing the same, and more particularly, to a liposome-microstructure comprising a liposome containing a skeleton material of a structure and a preparation method thereof.

Currently, commercialized drug delivery systems are largely divided into oral preparations, injections, and transdermal preparations. Among them, oral administration is the most common and convenient method, but it causes limitation of drug degeneration and absorption due to gastrointestinal tract, and most of proteins and DNA constructs such as insulin and hormone drugs are decomposed by the gastrointestinal tract and are difficult to be effectively used.

Injection is also the fastest and most effective method of drug delivery, but patient suffering and rejection of needles not only causes mental stress on the patient, but also requires the help of professional medical personnel and difficulties in repeated administration.

To overcome these disadvantages, new methods of transdermal administration have been developed. In the case of the transdermal drug delivery system, it is possible to avoid the gastrointestinal disorder by transferring the drug through the skin, and it is possible to reduce the pain and rejection of the patient when the drug is administered. However, in the case of transdermal drug delivery, the molecular weight of the drug delivered by the stratum corneum present in the outermost layer of the skin is only 500 Da or less, and there is a limit to an effective drug delivery system due to differences in the amount and rate of delivery depending on the type of drug .

In order to overcome this problem, new systems such as iontophoresis, electrophoresis, heating, microneedle, and chemical enhancer have been developed. However, there are limitations in transferring a sufficient amount of the drug.

In the case of the micro needle, a small hole is formed on the surface of the skin to deliver the drug, and the length can be adjusted to 90 ~ 1500 ㎛ according to the purpose of drug delivery. This form is a physical puncture of the horny layer, which is the outermost layer of the skin, through which the drug is delivered. However, these conventional microneedle systems are difficult to transfer sustained drug delivery due to the small size of the holes formed and the holes of the skin due to the passage of time. Especially, it is difficult to transfer nanocarrier such as nanoparticle and liposome through the holes formed. A system for delivering a drug into the skin by impregnating the drug inside the microneedle made of a water-soluble water-soluble polymer also has a limitation in delivering the liposome drug due to the water-soluble property of the microneedle structure.

In addition, when a drug is coated on a needle or dissolved in a water-soluble needle, it is difficult to control the release of drug and biological reaction by rapid dissolution and simple diffusion, and there is a risk of infection with a sharp needle structure after use.

As mentioned above, the existing micro needle system does not yet offer the safety, stability, and smart drug delivery characteristics required for transdermal delivery of medicines or cosmetics, but merely conveys the desired substance to the inside of the skin.

 The present invention provides a drug delivery structure capable of easily delivering a water-soluble or liposoluble drug.

The present invention relates to a smart transdermal drug delivery structure capable of delivering liposome-based microstructures having various drug delivery functions, and capable of delivering target-directed drugs to desired sites or cells by controlling the amount and rate of drug release.

One aspect of the invention pertains to liposome-microstructures comprising a liposome containing skeletal material of the delivery vehicle.

The present invention provides a liposome-microstructure formed by mixing and drying a liposome and a biocompatible material.

In another aspect, the invention provides a method of making a liposome comprising the steps of: preparing a liposome containing a delivery vehicle therein; And mixing the liposome with the biocompatible material to prepare a microstructure. The present invention also provides a method for producing a liposome-microstructure.

The present invention can deliver a water-soluble or liposoluble drug to a liposome and deliver the drug through the skin to the body, which has not been readily absorbed. According to the present invention, a microstructure having a simple structure can be provided by using a liposome having a drug delivery function as a skeleton of a microstructure.

The liposome-microstructures of the present invention can selectively and locally deliver drugs effectively and stably to desired sites such as cancer, muscle, and cell using the drug transfer characteristics of liposomes.

1 is a schematic view showing a liposome-microstructure, which is an embodiment of the present invention.
2 is a schematic view showing the shape of the liposome according to the present invention.
3 is a schematic view showing penetration of the liposome-microstructure into the skin according to the present invention.
Figure 4 compares the drug content in the liposomes before drying with the structure and the drug content in the liposomes after reconstituting the structure.
5 is a schematic view showing a step of preparing a liposome-microstructure in the present invention.
6 is an SEM image of the microstructures obtained in Example 1 and Comparative Example 1. Fig.
7 is an image of a fluorescence microscope of the liposome-microstructures obtained in Examples 1 to 4. Fig.
8 is a TEM photograph of the liposome (a) prepared in Example 1 and the liposome (b) prepared by using the liposome (a) and then redissolved again.

The present invention relates to a liposome-microstructure characterized in that the skeletal material of the construct comprises a liposome containing a delivery drug.

1 is a schematic view showing a liposome-microstructure, which is an embodiment of the present invention. Referring to FIG. 1, the liposome-microstructure includes a support plate 10 and a needle 20.

The liposome-microstructure is formed by a support plate 10 and a needle 20, preferably the needle 20, as a liposome skeleton.

The liposome-microstructures of the present invention can be realized with micro needles, micro spikes, micro-blades, micro knives, micro fibers, micro probes, micro barb, microarrays or micro electrodes, more preferably micro needles.

The liposome-microstructures may be formed by mixing and drying the liposome and the biocompatible material.

The liposome may be used as a liposome stabilizing agent. For example, the liposome may be selected from the group consisting of trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melitose, dextran, sorbitol, Tall, palatinit, or mannitol can be mixed with one or more than one. Such a stabilizer may be added to the interior of the liposome during the production of the liposome or may be added when the liposome and the biocompatible material are mixed together, or may be prepared by simultaneously adding the above methods. The amount of the stabilizer added may be in the range of 1.1 to 40 times the lipid added in the production of the liposome. The amount of the stabilizer added is not particularly limited, and it is preferable to find the most optimal ratio according to the liposome preparation method.

The liposome may be selected from the group consisting of trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melitose, dextran, sorbitol, xylitol, palatinite, mannitol, poly Poly (lactide), poly (glycolide), poly (lactide-co-glycolide), polyanhydride, polyorthoester, polyetherester, polycaprolactone, Polyacrylic acid, ethylene-vinyl acetate polymer, acrylic substituted cellulose acetate, non-degradable polyurethane, polystyrene, polyvinyl (meth) acrylate Poly (vinylimidazole), chlorosulfonate, chlorosulphonate polyolefins, polyethylene oxide, polyether sulfone, poly Polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxymethylcellulose, cyclodextrin and And a copolymer of monomers forming such a polymer. These additives may be added to the interior of the liposome when liposomes are prepared, or may be added when the liposome and the biocompatible material are mixed, , And the above method may be simultaneously added.

The liposomes may contain an aqueous delivery vehicle on the inside and a lipophilic drug in the non-polar portion.

2 is a schematic view showing the shape of the liposome according to the present invention. Referring to FIG. 2, the liposome according to the present invention comprises an inner layer 110 formed by a polar head portion and a non-polar portion 120 composed of a non-polar hydrocarbon chain. The non-polar portion 120 may contain the oil-soluble transport drug 140, and the water-soluble transport drug 130 may be contained on the inner portion.

There is no particular limitation on the delivery drug, but water-soluble, lipid-soluble drugs and the like can all be used. Such drugs include chemical drugs, protein drugs, peptide drugs, nucleic acid molecules and nanoparticles for gene therapy, efficacious substances used in cosmetics, water-containing functional substances, and medical antibodies such as interferon.

More specifically, the drugs that may be contained in the liposomes of the present invention include anti-inflammatory agents, analgesics, antiarthritics, antispasmodics, antidepressants, antipsychotics, neurotransmitters, anxiolytics, antagonists, antiparkins drugs, cholinergic agonists , Anticancer agents, anti-angiogenic agents, immunosuppressive agents, antiviral agents, antibiotics, appetite suppressants, analgesics, anticholinergics, antihistamines, anti-migraine agents, hormones, coronary blood vessels, cerebrovascular or peripheral vasodilators, A diuretic agent, an antihypertensive agent, a therapeutic agent for cardiovascular diseases, a cosmetic ingredient (for example, a wrinkle-reducing agent, a skin aging inhibitor and a skin lightening agent), and the like.

The protein / peptide medicament to be used in the present invention is not particularly limited, and may be a hormone, a hormone analogue, an enzyme, an enzyme inhibitor, a signal transduction protein or a part thereof, an antibody or a part thereof, a single chain antibody, But are not limited to, adhesion proteins, structural proteins, regulatory proteins, toxin proteins, cytokines, transcription factors, blood coagulation factors and vaccines. More specifically, the protein / peptide medicament may be selected from the group consisting of insulin, IGF-1 (insulin sensitization factor 1), growth hormone, erythropoietin, granulocyte-colony stimulating factors (G-CSFs), granulocyte / macrophage- interleukin-1, interleukin-6, interleukin-2, EGFs (epidermal growth factors), calcitonin, ACTH a tumor necrosis factor (TNF), an atobisban, a buserelin, a cetrorelix, a deslorelin, a desmopressin, a dyno Dynorphin A (1-13), elcatonin, eleidosin, eptifibatide, growth hormone releasing hormone-II (GHRH-II), gonadorelin ), Goserelin, histrelin, leuprorelin, lyphresin (ly pressin), octreotide, oxytocin, pitressin, secretin, sincalide, terlipressin, thymopentin, thymosine, ), Triptorelin, bivalirudin, carbetocin, cyclosporine, exedine, lanreotide, luteinizing hormone-releasing hormone (LHRH) Nafarelin, parathyroid hormone, pramlintide, T-20 (enfuvirtide), thymalfasin and chiconotide.

The liposome may further comprise an enhancer capable of increasing the stability of the liposome and enhancing the strength of the needle. It is preferable to use a water-soluble polymer as the thickener. Examples of the water-soluble polymer include polyvinyl alcohol, carboxyvinyl polymer, acrylic vinyl polymer, carboxymethylcellulose, hydroxyethylcellulose, xanthan gum, locust bean gum, ethylene-vinyl acetate polymer, acrylic substituted cellulose acetate, non- Polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylic acid, polymethacrylic acid, polystyrene, polyvinyl chloride, polyvinyl fluoride, poly (vinyl imidazole), chlorosulphonate polyolefins, A copolymer selected from the group consisting of hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxymethylcellulose, cyclodextrin and monomers forming such a polymer. It may be composed of two or more substances.

The presence of the thickener increases the viscosity of the aqueous solution inside the liposome, minimizing the release of the entrapped delivery drug and keeping the liposome in a stable state. In addition, when the liposoluble transport drug is present in the nonpolar portion, the liposome is maintained in a stable form by the internal thickening agent, so that the loss of the transport drug present in the nonpolar portion can be reduced.

More specifically, the liposome comprises an inner phase 110 comprising a delivery drug and a thickener aqueous solution 130, a non-polar portion 120 containing a liposoluble delivery drug 140, and a thickening or delivery drug, And includes a removed outer phase 150. The outer phase 150 removes the buildup and delivery medicines to facilitate skin penetration and needle production.

The liposome preferably has a size of 5-5000 nm, preferably 50-800 nm.

In the present invention, a biocompatible material together with the liposome is used as a skeleton material of the structure. The biocompatible material is substantially non-toxic to the human body, chemically inert and immunogen-free, and further, the biocompatible material for use in the present invention should be capable of being degraded by body fluids, microorganisms, and the like in vivo. The biocompatible material can be used without limitation as long as it meets the above conditions. Wherein the biocompatible material is selected from the group consisting of polylactide, polyglycolide (PGA), polylactide-glycolide copolymer (PLGA), hyaluronic acid, alginic acid, pectin, carrageenan, chondroitin (Sulphate), dextran (sulfate), chitosan, polylysine, collagen, gelatin, carboxymethyl chitin, fibrin, agarose, pullulan polyanhydride, polyorthoesters, polyetheresters, polycaprolactones, polyesteramides, poly (butyric acid), poly (valeric acid), polyurethanes, polyacrylates, ethylene-vinyl acetate polymers , Acrylic substituted cellulose acetate, non-degradable polyurethane, polystyrene, polyvinyl chloride, polyvinyl fluoride, poly (vinylimidazole), chlorosulfone Polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose ( HPC), carboxymethylcellulose, cyclodextrin, and copolymers of monomers that form such polymers, and celluloses.

The liposome-microstructure is formed by mixing and drying the liposome and the biocompatible material.

The content of the liposome is 0.0001 to 100%, preferably 3 to 70%, of the mass of the whole structure after drying. The content of the liposome may be variously changed depending on the concentration of the drug to be delivered and the shape of the microstructure, and includes all cases in which even a small amount of liposome is contained, without being limited to the above content.

The mixture of the hydrated liposome and the biocompatible material is dried to form the skeleton of the microstructure. The skeleton of the structure has sufficient hardness and strength to penetrate the stratum corneum of the skin.

The liposome not only forms the skeleton of the structure but also contains a lipid soluble or water soluble drug and can simultaneously function as a carrier for transferring the lipid to the target material.

That is, in the present invention, the liposome forms a skeleton of the structure while containing the carrier material, and when the structure is inserted into a living body, the liposome may be dissolved in the carrier containing the carrier drug to transfer the drug.

3 is a schematic view showing penetration of the liposome-microstructure into the skin according to the present invention. Referring to FIG. 3, it is shown that after the structure pierces the stratum corneum of the skin, the liposome dissolves with the drug and penetrates into the skin.

Figure 4 compares the drug content in the liposomes before drying with the structure and the drug content in the liposomes after reconstituting the structure. Referring to FIG. 4, it can be confirmed that the liposome contains a drug even after being dried and re-dissolved.

In another aspect, the invention provides a method of making a liposome comprising the steps of: preparing a liposome containing a delivery vehicle therein; And mixing the liposome with the biocompatible material to prepare a microstructure. The present invention also provides a method for producing a liposome-microstructure.

Liposome  Manufacturing stage

This step is to prepare a liposome containing the delivery drug from a mixed solution comprising lipid, carrier drug and water. The step may further comprise an enhancer within the liposome that can enhance the stability of the liposome and increase the mechanical strength of the needle.

The liposome can be produced by a variety of conventional methods for producing liposomes such as a conventional mechanical force, a detergent removing method, a solvent injection method, and a reverse phase evaporation method. The mechanical force method is a method of making a lipid thin film or powder, applying the lipid to a substance to be water-soluble liposomes, and then applying strong agitation, strong pressure, or using ultrasonic waves.

The detergent removing method is a method in which the phospholipid is dispersed using a detergent solution and then the detergent is removed by dialysis. In the solvent injection method, phospholipid is dissolved in a solvent and then injected into an aqueous solution. The reverse phase evaporation method is a method in which phospholipid is dissolved in an organic solvent It is a method of making a post-hatch type emulsion and removing the solvent.

According to the method of the present invention, all of the above methods can be used, and it is preferable to select an appropriate method depending on the size of the liposome and the content of the liposome.

The step of preparing the liposome may be a step of hydrating the lipid after mixing lipid, carrier drug, and water.

The step of preparing the liposome may be a step of further hydrating the lipid after further mixing at least one of the stabilizer and the thickener.

The liposome preparation method (if further comprising the thickening agent) can be first mixed with lipid, delivery drug, stabilizer, thickener and water. More specifically, the method may include forming lipid into a thin film, mixing the lipid of the thin film with a water-soluble carrier drug, a stabilizer, a water-soluble thickener, and water, and hydrating the lipid.

In the above method, the stabilizer, the thickening agent, the carrier drug, and the water may be added respectively, or the aqueous thickener, the stabilizer or the aqueous carrier may be used.

On the other hand, in the case where the liposome contains a lipid soluble drug as a delivery drug, for example, first, a lipid and a lipid-soluble transport drug are formed into a thin film, a lipid and liposoluble transport drug is mixed with a water- And then hydrating the lipid. The liposome produced by the above method may contain the oil-soluble transport drug in the non-polar portion, and the aqueous solution may contain the aqueous solution in which the thickener dissolves.

The hydration is preferably performed by dispersing the lipid in water with a multi-lamellar vesicle (MLV) to hydrate.

There is no particular limitation on the stirring speed or time of the mixed solution in the hydration step.

The hydration may be performed by dispersing the lipid with a multi-lamellar vesicle (MLV) and hydrating the lipid of the thin film before mixing with the aqueous transporting drug, thickening agent and water, followed by ultrasonic treatment or mechanical stirring . As a result, the lipid attached to the inside of the reactor in the form of a thin film can be separated and easily mixed with an aqueous solution and hydrated.

The hydration step will be described in more detail by taking the case of phospholipid as an example. Phospholipids consist of anionic, or ampholytic, polar head and a nonpolar hydrocarbon chain. It is the hydrophobic interactions between the hydrocarbon chains and the electrostatic repulsion of hydrophilic molecular chains that lipids spontaneously form spheres. The number of water molecules hydrated in the head of the phospholipid and the intensity of the water-lipid interaction influence the formation and properties of the liposomes.

When a water-soluble carrier drug is used through such a formation process, a water-soluble thickener and a water-soluble carrier drug dissolve in water and are present as an aqueous solution, and the aqueous solution is contained in the inner part of the liposome.

On the other hand, in the case of the oil-soluble transport drug, the transport drug exists in the non-polar portion and the inner aqueous solution contains only the increasing agent dissolved therein.

Increasing agents that can be used in the present invention increase the viscosity of the aqueous solution within the liposomes to minimize the release of the entrapped delivery drug and to keep the liposomes stable. When increasing the viscosity of the aqueous solution, the viscosity may range from 1 to 55 cps, preferably from 1 to 20 cps. The concentration of the thickener dissolved in the aqueous solution may range from 1 to 10%, preferably from 1 to 5%. In this range, the size change of the liposome with time is small, so that a more stable structure can be maintained.

The lipid may be one or more of fat, phospholipids, steroids and carotene.

It is preferable to use a water-soluble polymer as the thickener. As the water-soluble polymer, polyvinyl alcohol, carboxyvinyl polymer, acrylic vinyl polymer, carboxymethyl cellulose, hydroxyethyl cellulose, xanthan gum, locust bean gum, or a mixture thereof may be used. The incremental zero is most preferably polyvinyl alcohol (PVA).

Preparation step of microstructure

This step is a step of mixing the hydrated liposome with the biocompatible material and drying to prepare the structure.

       For example, the step of preparing the liposome is a step of hydrating the lipid after mixing the lipid of the thin film with the carrier drug, the stabilizer, the thickener, and water. The stabilizer added is 1.1 The amount of the stabilizer added is not particularly limited, and it is preferable to find the most optimal ratio according to the liposome preparation method.

The content of the liposome is 0.0001 to 70%, preferably 3 to 70%, of the mass of the whole structure after drying. The content of the liposome may be variously changed depending on the concentration of the drug to be delivered and the shape of the microstructure, and includes all cases in which even a small amount of liposome is contained, without being limited to the above content. The constituent materials of the microstructure mainly include liposomes, biocompatible materials, stabilizers, and the like, and their composition ratios can be variously changed depending on the mode or mode to be delivered.

The microstructure may be formed using the mixture. The above-mentioned structure manufacturing method can use any conventionally known methods without limitation. For example, Japanese Patent Application Laid-Open No. 2005154321 proposed by Nano Device & And " Sugar Micro Needles as Transdermic Drug Delivery System " (Biomedical Microdevices 7: 3, 185-188, 2005). Further, a method of producing a biodegradable polymer micro-needle by making a template by photolithography (Fabrication, mechanics and transdermal drug delivery, Journal of Controlled Release 104, 51-66, 2005) can be referred to.

In addition, a known soft lithography technique may be used to prepare an elastomeric mold such as PDMS (polydimethylsiloxane) and use it in the production of liposome-microstructures. The PDMS mold manufacturing technology is a kind of plastic processing technique, and a desired molding structure can be obtained by various methods such as casting, injection, hot-embossing, and the like. For example, a photosensitive material is coated on a substrate such as a silicon wafer or glass, and patterned using a photomask, resulting in a master. When the PDMS is cast and sintered with the mold, a PDMS mold having a stamp function can be completed.

More specifically, in the present invention, the step of preparing the microstructure includes injecting a mixture of the liposome and the biocompatible material into a cavity of a micro-mold and drying the micro-structure; And removing the micro-mold.

5 is a schematic view showing a step of preparing a liposome-microstructure in the present invention. Referring to Figure 5, the method comprises the steps of (a) providing a micro-mold, (b) feeding a mixture of the liposome and a biocompatible material onto the micro-mold, (c) injecting the mixture into a hole formed in the mold, (D) drying it, and (e) removing the mold.

Hereinafter, the present invention will be described in more detail with reference to examples, but these examples should not be construed as limiting the scope of protection of the present invention.

Example  One

5 ml of chloroform was added to a round flask, and 100 mg of phospholipid (Soybean phosphatidylcholine (PC)) and phosphatidylethanolamine rhodamine were dissolved therein. The flask was then placed in a rotary evaporator and the chloroform was evaporated overnight, resulting in a thin film on the bottom of the flask, which was then placed in an oven or incubator for about 30 minutes to remove any remaining chloroform. The model drug calcein and the stabilizer trehalose were added to the thin film thus prepared. At this time, the concentration of the calcine solution is 20 mM and the concentration of added trihalose is 50-400 mM. 10 ml of a solution of calcein-trihalose was added and the lipids attached to the bottom of the flask were all hydrated for 1 hour to obtain a Multi-lamella vesicle liposome. A mixed solution of the liposome thus obtained and carboxymethyl cellulose (CMC) was prepared, and the content of the liposome prepared was 3% of the mass of the dried whole structure.

Subsequently, the mixed solution was supplied to the PDMS micro mold, and the mixed solution was injected into the holes formed in the mold using a centrifuge process. After drying at 25 DEG C for 3 hours, the mold was removed to obtain a liposome-microstructure.

Example  2

The procedure of Example 1 was repeated, except that the content of the liposome was changed to 15% in Example 1 to prepare a mixed solution.

Example  3

The same procedure as in Example 1 was carried out except that the mixed solution was prepared by adjusting the content of the liposome to 30% in Example 1.

Example  4

The procedure of Example 1 was repeated, except that the content of the liposome was changed to 60% in Example 1 to prepare a mixed solution.

Comparative Example  One

Unlike Example 1, a microstructure was prepared using carboxymethyl cellulose (CMC) without adding liposomes.

6 is an SEM image of the microstructures obtained in Example 1 and Comparative Example 1. Fig. Referring to FIG. 6, it can be confirmed that the shape of Example 1 prepared by containing the liposome is the same as that of Comparative Example 1 containing no liposome.

7 is an image of a fluorescence microscope of the liposome-microstructures obtained in Examples 1 to 4. Fig. Referring to FIG. 7, it can be seen that Example 4 having a high liposome content shows the reddish color, which indicates that Example 4 contains more liposomes in the skeleton than Examples 1 to 3.

8 is a TEM photograph of the liposome (a) prepared in Example 1 and the liposome (b) prepared by using the liposome (a) and then redissolved again. Referring to Fig. 7, it can be confirmed that the shape of the liposome (b) remains unchanged even after redissolution.

Claims (14)

A support plate and a needle,
Wherein the needle is a liposome skeleton formed by mixing and drying a biocompatible material and a liposome containing a delivery drug, wherein the liposome content is 0.0001 to 70% based on the total mass of the liposome skeleton,
The liposome may contain an aqueous delivery vehicle in its inner phase or may contain a lipophilic drug in the nonpolar portion,
The liposome forms the needle together with the biocompatible material while containing the transportation drug. When the needle is inserted into the living body, the liposome dissolves in the container containing the transportation drug and delivers the transportation drug into the living body ≪ / RTI > delete The composition of claim 1 wherein the liposome is selected from the group consisting of trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melitose, dextran, sorbitol, xylitol, palatinite, ≪ / RTI > wherein the liposome comprises at least one stabilizer. 2. The composition of claim 1, wherein the liposome further comprises an enhancer capable of increasing the viscosity of the interior, wherein the incremental agent is selected from the group consisting of polyvinyl alcohol, carboxyvinyl polymer, acrylic vinyl polymer, carboxymethylcellulose, hydroxyethylcellulose, Polyvinyl chloride, polyvinyl fluoride, poly (vinylimidazole), chlorosulphonate, polyolefin (chlorosulphonate), polyvinyl chloride, polyvinyl pyrrolidone, polyvinyl pyrrolidone, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxy Methylcellulose, cyclodextrin, and monomers of these polymers Liposomes of the group consisting of a polymer to be the selected of one or more water-soluble polymers ranging in-microstructures. The liposome according to claim 1, wherein the liposome is selected from the group consisting of trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melitose, dextran, sorbitol, xylitol, It is also possible to use a polymeric material such as a knit, mannitol, poly (lactide), poly (glycolide), poly (lactide-co-glycolide), polyanhydride, polyorthoester, polyetherester, But are not limited to, polycaprolactone, polyesteramide, poly (butyric acid), poly (valeric acid), polyurethane, polyacrylate, ethylene-vinyl acetate polymer, acrylic substituted cellulose acetate, Polyvinyl chloride, polyvinyl fluoride, poly (vinylimidazole), chlorosulfonate, chlorosulphonate polyolefins, polyethyl (meth) acrylate, Polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxymethylcellulose , A cyclodextrin, and a copolymer of monomers forming such a polymer. The liposome-microstructure according to any one of claims 1 to 3, delete delete delete The method of claim 1, wherein the biocompatible material is selected from the group consisting of hyaluronic acid, alginic acid, pectin, carrageenan, chondroitin (sulfate), dextran (sulfate), chitosan, polylysine, , Collagen, gelatin, carboxymethyl chitin, fibrin, agarose, pullulan polylactide, polyglycolide (PGA), polylactide-glycolidide copolymer (PLGA), hyaluronic acid Alginic acid, pectin, carrageenan, chondroitin (sulfate), dextran (sulfate), chitosan, polylysine, collagen, gelatin, carboxymethyl chitin, fibrin, agarose, Polyanhydride, polyorthoester, polyetherester, polycaprolactone, polyesteramide, poly (butyric acid), polyacrylic acid, Poly (vinylidene chloride), poly (vinylidene chloride), poly (vinylidene chloride), poly (vinylidene chloride), poly Polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylmethylcellulose Wherein the liposome is at least one selected from the group consisting of cellulose (HPC), carboxymethylcellulose, cyclodextrin, copolymers of monomers forming such polymers, and cellulose. Preparing a liposome containing a delivery drug therein;
Injecting a mixture of the liposome and the biocompatible material into a cavity of a micro-mold and drying the mixture; And
And removing the micro-mold, the method comprising the steps of:
Wherein the step of preparing the liposome is a step of hydrating the lipid after mixing the lipid, the delivery drug, and water, wherein the delivery drug is a water soluble or lipid soluble drug, wherein the liposome contains a water soluble drug, Wherein the liposome forms a skeleton of the structure together with the biocompatible material while containing the transporting drug in the drying step and the content of the liposome is 0.0001 to 70% ≪ / RTI > wherein the liposome-microstructure is a liposome. delete [Claim 11] The method according to claim 10, wherein the step of preparing the liposome is a step of hydrating the lipid after further mixing at least one of the stabilizer and the thickener.


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