WO2019124581A1 - Liposome particles supporting functional material and having controllable particle size and manufacturing method therefor - Google Patents

Abstract

The present invention relates to liposome particles surface-treated with silica and a manufacturing method therefor and, more specifically, to liposome particles surface-treated with silica and used for supporting a functional material, and to a manufacturing method for liposome particles surface-treated with silica, wherein the liposome particle size can be controlled according to the stirring rate. According to the present invention, the silica size-control type liposome particles by the present invention are manufactured such that a liposome surface is fixed by silica, and thus liposome particles having a double membrane having stability against an external environment can be provided. Particularly, the liposome particles manufactured according to the present invention are excellent as a support for a functional material since the liposome particles are hollow and stable against an external environment.

Description

Liposome Particles Capable of Carrying Functional Substance and Controlling Size of Particles and Method for Manufacturing the Same

The present invention relates to a liposome particle capable of supporting a functional substance and a method for producing the liposome particle. More particularly, the present invention relates to a liposome particle capable of supporting a functional material by surface- To a process for producing liposome particles.

Various materials such as silica (SiO ₂ ), zeolite, and hydrogel are widely used as the material to be used as the functional material support, though they depend on the characteristics of the material to be supported . Liposomes are used as mediators for transferring substances by moving various drugs and functional substances including anticancer drugs, antimicrobial drugs, antigens, antibodies, and proteins.

Liposome is a structure in which lecithin, similar to skin constituents, is wrapped around a layer of active ingredients. When lecithin is dissolved in an aqueous solution at the same ratio as the composition of the cell membrane, a bilayer structure composed of two layers is formed. Liposome molecules are divided into two layers to minimize water surface area and remain stable by van der Waals force. Since the inside of the layer is hydrophobic, most of the water-soluble materials can not penetrate into the inside of the double-layer structure, so that the functional material can be selected and supported using these characteristics.

However, these liposomes are apt to become structurally unstable due to physical impact. If the structure becomes unstable, the substances carried on the inside are released to the outside, so that there is a problem in liposome function as a carrier, which makes it difficult to stabilize the formulation.

Accordingly, liposomes are prepared as a carrier by controlling particle size, lipid component, charge permeation, etc. in order to control physically, chemically and microbiologically unstable factors.

The inventors of the present invention have made extensive efforts to overcome the problems of the prior art. As a result, when the surface of the inner and outer surfaces of the liposome is treated with silica, the stability of the liposome unstable due to physical stimulation can be increased. And thus it was confirmed that it was excellent as a carrier for carrying a functional material, and the present invention was completed.

Accordingly, it is an object of the present invention to provide a liposome particle for supporting a functional substance, whose surface is treated with silica, as a carrier for supporting a functional substance, which is stable from changes in the external environment.

Another object of the present invention is to provide a method for producing liposome particles for supporting a functional material surface-treated with silica according to the present invention.

According to one aspect of the present invention, there is provided a liposome particle for supporting a functional material surface-treated with silica.

Liposomes have been used as mediators for the transfer of functional materials by their structural properties, but their stability to the external environment has been low, limiting their use as carriers. Thus, the present inventors confirmed that when the surface of the liposome particles is surface-treated with silica, stability from the external environment can be enhanced, and that the inside of the liposome is empty, so that it is easy to support the functional substance, thereby completing the present invention .

The liposome particle for supporting a functional substance of the present invention contains hollows therein, and the inner hollow surface is also surface-treated with silica. The liposome particle according to the present invention has a structure including a hollow therein, and the silica is coated not only on the inner surface but also on the inner hollow surface.

In the liposome particle for supporting a functional material of the present invention, the liposome particle has a diameter of 0.5 to 5 μm.

In the liposome particle for supporting a functional material of the present invention, the silica is characterized by coating 15 to 18% of the surface of the liposome.

The liposome particles for supporting functional material of the present invention are characterized in that mass reduction occurs in the range of 90 to 110 ° C and 300 to 400 ° C in TGA analysis.

According to one experimental example of the present invention, the weight loss rate of lecithin and the remaining percentage of silica in the particles agitated for 4 hours were checked, and as a result, weight loss by moisture at 100 캜 was confirmed. As a result, the weight loss by lecithin was confirmed in the range of 300 to 400 ° C, and the weight loss by the unreacted silane group was confirmed in the range of 400 to 500 ° C. Based on this, it was confirmed that 15 to 18% of the surface of the silica size-controlled liposome particles was coated with silica (see FIG. 4).

The liposome particle for supporting a functional substance of the present invention is characterized in that a peak appears at 1000 to 1200 cm ^-1 under FT-IR analysis.

According to another aspect of the present invention,

A) mixing ethanol, purified water and lecithin in a ratio of 2: 1: 0.04, and then stirring to prepare a solution in which liposome particles are dispersed;

B) mixing a silica precursor with a solution in which the liposome particles are dispersed in step A) and stirring the liposome surface to treat the liposome surface with silica; And

C) centrifuging the solution of step B) to separate the liposome surface-treated with silica; And

D) washing and drying the liposome surface-treated with the separated silica; The present invention also provides a method for producing a liposome particle surface-treated with silica comprising

In the method of the present invention, the silica precursor may be tetraethyl orthosilicate, tetramethyl orthosilicate, or a mixture thereof. In the present invention, Tetraethyl orthosilicate was used.

In the method for producing liposome particles surface-treated with silica of the present invention, the stirring in the step B) is performed for 4 to 24 hours.

In the method for producing a liposome particle surface-treated with silica according to the present invention, the size of liposome particles produced according to the agitation time in the step B) can be controlled.

According to an experimental example of the present invention, the size of the liposome particles surface-treated with silica can be adjusted to 0.5 to 5 μm according to the stirring time, and when the stirring time is 4 hours or less, When the stirring time is longer than 24 hours, there is a problem that the liposome particles are too small to support the functional material, and therefore, it is difficult to function as a carrier (see FIG. 2).

The liposome particle capable of supporting the functional material according to the present invention is excellent as a carrier of a functional substance because the liposome particle is empty and has a double membrane and is stable to the external environment by surface treatment of the inner and outer surfaces with silica. In addition, in the method of manufacturing the liposome particles capable of supporting the functional material according to the present invention, it is possible to produce particles of desired size by controlling the stirring speed.

Figure 1 shows a schematic diagram of the development of the silica size controlled liposome particle of the present invention.

Figure 2 shows SEM photographs of the silica size controlled liposome particles prepared according to the present invention.

Figure 3 shows the FT-IR measurement results of the silica size controlled liposome particles prepared according to the present invention.

Figure 4 shows the TGA results of the silica size controlled liposome particles prepared according to the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. These embodiments are only for illustrating the present invention, and thus the scope of the present invention is not construed as being limited by these embodiments.

<Example> Production of silica size-controlled liposome particles

Lecithin was purchased from TCI for 1,2-diacyl-sn-glycero-3-phosphatidylcholine and Tetraethyl orthosilicate (TEOS) was purchased from Sigma Aldrich for use in the preparation of liposomes.

Lecithin is dissolved in ethanol at a ratio of 1: 0.018, then 1/2 of the volume of ethanol is added at room temperature, and the mixture is stirred for 20 minutes. After this, the solution was ultrasonically dispersed for 10 minutes, the temperature was raised to 60 캜 and stirred for 4 hours.

After the temperature of the lecithin dispersion solution was lowered, the silica precursor was adjusted to a volume ratio of lecithin: silica precursor = 1: 5.4, and the solution was slowly dropped to react. The mixture was stirred for 4 hours to 24 hours while being stirred at room temperature .

After separating the particles produced by the centrifugal separator and unreacted lecithin and silica particles, only the generated particles were washed with water and ethanol and dried in an oven at room temperature to prepare particles.

<Experimental Example>

Experimental Example 1: SEM measurement

SEM photographs of particles prepared by stirring for 4 hours prepared in the above example were measured and the results are shown in Figs. 1 and 2. Fig.

As can be seen from FIGS. 1 and 2, it can be seen that the liposome particles are uniformly produced at a size of about 1 to 2 μm, and that the inside of the silica particles forms hollow hollows .

In addition, it can be confirmed that the particle size is controlled as the size of the particles decreases with the agitation time when the agitation time is changed.

Experimental Example 2: FT-IR measurement

The liposome particles prepared by stirring in the above-mentioned example for 4 hours were confirmed by Fourier transform infrared spectroscopy (FT-IR).

As a result, as shown in FIG. 3, the peaks at 2900 cm ^-1 and 1750 cm ^{-1 of} the CH and C═O functional groups of lecithin and at 1100 cm ^-1 of the Si-O-Si structure of silica .

Experimental Example 3: TGA measurement

The pyrolysis characteristics of the liposome particles prepared in the above Examples were confirmed by TGA (Thermogravimetric analysis), and the results are shown in FIG.

As shown in FIG. 4, when the liposome particles prepared by stirring for 4 hours were observed, the weight loss rate by lecithin and the residual ratio by silica were found to be 100% Weight loss by lecithin could be confirmed in the range of 300 to 400 ° C. Finally, weight loss due to unreacted silane groups in the range of 400 to 500 ° C can be seen.

Based on this, it was confirmed that the silica of the silica size control type liposome particles was coated with 18.05% of the surface.

As described above, the liposome particles for supporting functional materials according to the present invention are excellent in stability for supporting functional materials by surface-treating the inner and outer surfaces with silica. In addition, the liposome particles of the present invention can produce liposome particles having a desired size by controlling the stirring speed.

Claims (10)

1. Liposome particles for supporting functional materials surface-treated with silica.
2. The method according to claim 1,

   Wherein the liposome particle comprises an inner hollow surface treated with silica.
3. The method according to claim 1,

   Wherein the liposome particles have a diameter of 0.5 to 5 [mu] m

   Liposome particles for supporting functional materials.
4. The method according to claim 1,

   Wherein 15 to 18% of the surface of the liposome particle surface is surface-treated with silica

   Liposome particles for supporting functional materials.
5. The method of claim 1, wherein

   The liposome particles exhibit a mass reduction in the range of 90 to 110 DEG C and 300 to 400 DEG C in TGA analysis

   Liposome Particles for Supporting Functional Substance
6. The method of claim 1, wherein

   The liposome particles have peaks at 1000 to 1200 cm &lt; ^-1 &gt; at FT-IR analysis

   Liposome Particles for Supporting Functional Substance
7. A) mixing ethanol, purified water and lecithin in a ratio of 2: 1: 0.04, and then stirring to prepare a solution in which liposome particles are dispersed;

   B) mixing a silica precursor with a solution in which the liposome particles are dispersed in step A) and stirring the liposome surface to treat the liposome surface with silica; And

   C) centrifuging the solution of step B) to separate the liposome surface-treated with silica; And

   D) washing and drying the liposome surface-treated with the separated silica; &Lt; / RTI &gt; wherein the liposome particles are surface-treated with silica.
8. 8. The method of claim 7,

   The silica precursor may be tetraethyl orthosilicate, tetramethyl orthosilicate, or a mixture thereof.

   A method for producing liposome particles surface-treated with silica.
9. 8. The method of claim 7,

   The stirring time of the step B) is controlled according to the particle size to be produced.

   A method for producing a liposome surface-treated with silica.
10. 8. The method of claim 7,

    Wherein the stirring in the step B) is carried out for 4 to 24 hours

    A method for producing a liposome surface-treated with silica.

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