KR101609047B1 - Polymer microparticle with a porous structure and process for preparing the same - Google Patents

Abstract

The present invention relates to a method for preparing a polymer electrolyte membrane, comprising: preparing a spray liquid containing a polymer; Spraying the prepared spraying stock solution while applying a voltage to produce porous polymer microparticles; Applying a vacuum to the porous polymeric microparticles to incorporate the drug; And immersing the drug-containing porous polymer microparticles in a diluted organic solvent solution to dissolve the surface of the porous polymer microparticles, thereby closing the holes in the surface of the microparticles. It is about.

Description

TECHNICAL FIELD [0001] The present invention relates to a porous polymer microparticle and a method for preparing the porous microparticle,

TECHNICAL FIELD The present invention relates to a drug delivery microparticle for sustained drug delivery, which maintains physiological activity without denaturing the drug, and a method for producing the same.

The development of biotechnology and pharmaceutical fields has revealed the functions and roles of proteins or peptides in detail. Protein drugs are being commercialized as therapeutic substances through their mass production. Although the efforts for the development of new drugs using these drugs are continuing, protein drugs have excellent physiological activity, but their bioavailability is very low because they are easily denatured or decomposed due to process parameters such as heat or toxic solvent and surfactant Therefore, there is a need to develop a drug delivery system capable of stably transferring the three-dimensional structure because of its physiological activity. Conventional processes for preparing polymeric particle transporters include processes using emulsion, spray drying, ionic interaction, phase separation and the like. However, In the case of drug preparations, there is a risk of denaturation of the drug, a short sustained release effect, a very small application range, and a high cost in production. As described above, the formulation using the polymer microparticles for the protein drug is difficult to commercialize due to problems such as denaturation of the drug, excessive release of the initial drug, and short-duration release effect during the manufacturing process, and the development process thereof is also complicated.

Korean Patent Registration No. 10-1096679

It is an object of the present invention to provide a method for producing porous polymer microparticles using an electrospray process.

Another object of the present invention is to provide porous polymer microparticles produced by the above-mentioned production method.

The present invention provides a method for producing porous polymer microparticles using an electrospray process.

More specifically,

Preparing a spraying stock solution containing the polymer;

Spraying the prepared spraying stock solution while applying a voltage to produce porous polymer microparticles;

Applying a vacuum to the porous polymeric microparticles to incorporate the drug; And

Immersing the drug-containing porous polymer microparticles in a diluted organic solvent solution to dissolve the surface of the porous polymer microparticles, thereby closing the holes on the surface of the microparticles;

The present invention also provides a method for producing porous polymer microparticles.

The polymer may be a biodegradable and biocompatible polymer. Specifically, the polymer may be a poly (D, L-lactide-co-glycolide) (Poly D, L-lactide-co-glycolide, PLGA) and Polycaprolactone (PCL).

The spraying stock solution containing the polymer may be in a concentration of 1 to 20% by weight.

The spraying liquid may include an organic solvent having a high volatility point, and may be specifically dimethyl sulfoxide (DMSO), acetonitrile, or dimethyl carbonate.

In the step of producing the porous polymer microparticles, the voltage may be applied while being applied in a range of 10 to 20 kV.

The drug may be selected from the group consisting of a protein, a peptide, a hydrophobic drug, a hydrophilic drug or an insoluble drug.

In another aspect, the present invention provides a porous polymer microparticle prepared by the above method.

The porous poly (D, L-lactide-co-glycolide) microparticles according to the present invention have no initial excess release of the protein and can be used as an injectable or oral drug (D, L-lactide-co-glycolide) microspheres without modification of bovine serum albumin (BSA) The present invention is advantageous in that the protein is successfully incorporated into the particles and is simple to manufacture and does not use a toxic solvent, heat, or surfactant, can incorporate a large amount of protein, It can be widely applied to fields requiring the transfer of other water-soluble molecules or proteins.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view illustrating a method for producing a microparticle for protein delivery according to an embodiment of the present invention. FIG.
FIG. 2 is a graph showing the effect of poly (D, L-lactide-co-glycolide) on the poly (D, L-lactide-co- glycolide) concentration via a scanning electron microscope (D, L-lactide-co-glycolide) microparticles according to the morphological change (A) and the concentration of various poly (D, L-lactide-co-glycolide) Graph (B).
Figure 3 is a scanning electron micrograph showing 7% by weight of porous poly (D, L-lactide-co-glycolide) microparticles in cross-section of the particles before and after blocking the surface pores with a dimethylsulfoxide solvent (Section A and surface C) and after solvent treatment (section B and surface D).
FIG. 4 is a photograph of a micrograph of a confocal microscope (before and after the incorporation of fluorescent isothiocyanate dextran into microparticles of porous poly (D, L-lactide-co-glycolide) The white lines are the approximate fluorescence sensitivities of the respective poly (D, L-lactide-co-glycolide) microparticles) (A) and the poly (D, L-lact) incorporating the phosphor isothiocyanate dextran (B) showing the quantitative fluorescence sensitivities before and after the solvent treatment of the microparticles of the present invention.
FIG. 5 is a graph showing the relationship between the circular polarization dichroism spectrum (A) of bovine serum albumin and the bovine serum of poly (D, L-lactide-co-glycolide) microparticles exposed to various ratios of phosphate buffered saline and dimethylsulfoxide mixture (B) showing albumin release behavior.

Hereinafter, the present invention will be described in detail.

According to the present invention,

The manufacturing method includes: preparing a spraying stock solution containing a polymer;

Spraying the prepared spraying stock solution while applying a voltage to produce porous polymer microparticles;

Applying a vacuum to the porous polymeric microparticles to incorporate the drug; And

Immersing the drug-containing porous polymer microparticles in a diluted organic solvent solution to dissolve the surface of the porous polymer microparticles, thereby closing the holes on the surface of the microparticles;

The present invention also provides a method for producing porous polymer microparticles.

The polymer may be a polymer having biodegradability and biocompatibility. Specifically, the polymer is a poly (D, L-lactide-co-glycolide) (poly (D, L-lactide-co- glycolide) But are not necessarily limited to, those selected from the group comprising Polycaprolactone (PCL).

The undiluted solution containing the polymer may have a concentration of 1 to 20% by weight. If the weight of the polymer is increased beyond the above range, the porosity of the microparticles may be decreased, which may result in poor drug penetration.

The spraying stock solution may contain an organic solvent having a high volatility point. Specifically, the spraying liquid may be an organic solvent selected from the group consisting of dimethyl sulfoxide (DMSO), acetonitrile, and dimethyl carbonate, but is not limited thereto. Dimethyl sulfoxide (DMSO).

In the step of producing the porous polymer microparticles, the voltage may be applied while being applied in a range of 10 to 20 kV. If the voltage is out of the above-mentioned range, it may be difficult to produce uniform porous polymer microparticles.

The drug may be selected from the group consisting of a protein, a peptide, a hydrophobic drug, a hydrophilic drug or an insoluble drug. Specifically, the drug may be a recombinant human bone morphogenetic protein (rhBMP) -1, rhBMP-2, a recombinant human vascular endothelial growth factor (rhVEGF), a recombinant human fibroblast growth factor (rhFGF) But are not limited to, soluble growth factors. In particular, it is preferably a protein or a peptide.

The present invention provides porous polymer microparticles prepared by the method according to the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view illustrating a method for producing a microparticle for protein delivery according to an embodiment of the present invention. FIG. The porous polymer microparticles are prepared by preparing microporous polymer microparticles, applying a vacuum to the microporous polymer microparticles, immersing the drug in the organic solvent solution diluted with the porous polymer microparticles in which the drug is impregnated, To thereby close the holes on the surface of the microparticles.

The polymer microparticles according to the present invention can be contained in microparticles without denaturing the drug. Also, since the surface of the microparticles is closed, release of the sustained release drug is possible without excess release of the initial drug.

The protein incorporation process according to the present invention uses a solvent that is not toxic, that is, it has little effect on cells, does not use a surfactant, and does not cause protein denaturation because there is no change in pH.

Generally, three types of shapes, such as spherical, sphere-on-string, and fiber-shaped, can control the process parameters such as concentration of polymer, solvent, applied voltage, You can control its shape through Among these fixed variables, the concentration of the polymer solution is an important point in determining the morphology of the drug delivery system.

In a specific embodiment of the present invention, a solution of poly (D, L-lactide-co-glycolide) (D, L-lactide-co- glycolide) dissolved in dimethyl sulfoxide at various concentrations When the concentration of poly (D, L-lactide-co-glycolide) was less than 7%, spherical shape was observed. When the concentration was 10%, a sphere-on (D, L-lactide-co-glycolide), the structure of the porous structure was further increased When the concentration of poly (D, L-lactide-co-glycolide) was 5 wt%, it was difficult to maintain high porosity due to breakage. And the average size of the microparticles was found to be less than that of poly (D, L-lactide-co- (D, L-lactide-co-glycolide) polymer increased from 2.90 ± 0.72 μm to 6.23 ± 1.13 μm as the concentration of the poly (D, The microparticles showed a relatively uniform size with a coefficient of variation of 9.6% when the poly (D, L-lactide-co-glycolide) polymer concentration was 7 wt% (D, L-lactide-co-glycolide) microparticles to be prepared for protein incorporation experiments, considering porosity, physical properties and uniform size of the (D, L-lactide-co- A concentration of 7% by weight was appropriate.

In a specific embodiment of the present invention, the temperature of the room at which electrospray is carried out is 26 ° C., which is higher than 19 ° C., the melting point of dimethylsulfoxide, of poly (D, L-lactide-co-glycolide) , L-lactide-co-glycolide) microparticles did not influence the crystallization of the dimethylsulfoxide solution in forming the porosity of the microparticles. The pore formation was analyzed through phase separation of the solvent with evaporation of the solvent during the electrospray, and if the dimethylsulfoxide had not completely evaporated during the electrospray process, the poly (D, L-lactide-co-glycol The large surface area of the electrosprayed microdroplet was found to be much higher than the vaporization point of dimethylsulfoxide, even at 189 ° C, And it was responsible for facilitating to be fast evaporating.

In addition, poly (D, L-lactide-co-glycolide) (Poly (D, L-lactide-co- glycolide)) is used to remove residual dimethyl sulfoxide through washing with phosphate- buffered saline , L-lactide-co-glycolide) microparticles.

In a specific embodiment of the present invention, the size of the surface pores of the poly (D, L-lactide-co-glycolide) microparticles was 62.7 +/- 8.5 nm, It was observed that the inner pore was larger than the pores on the surface (Figure 3). This phenomenon was observed in the emulsification and solvent evaporation methods, because the electrosprayed micro-droplet was caused by the rapid evaporation of the solvent between the oil and air The poly (D, L-lactide-co-glycolide) molecules in the microdroplets move continuously to the surface and precipitate during the electrospray process, resulting in relative It has a dense surface and a porous interior, which allows the small pores on the surface to be easily blocked and the large porosity on the inside, which is advantageous for incorporating large amounts of protein A.

In one specific embodiment of the present invention, a phosphate buffered saline and dimethylsulfoxide mixture was used to close the pores of the microparticle surface. Dimethyl sulfoxide was used selectively because it had little effect on denaturation of the protein due to its relatively low toxicity. When the ratio of dimethyl sulfoxide was higher than 30 w / w%, a large lump was formed due to the tendency of the porous poly (D, L-lactide-co-glycolide) microparticles to join with each other. Thus, the mixing ratio of the dimethyl sulfoxide and the phosphate buffered saline solution was maintained at 20 w / w%, and all of the poly (D, L-lactide-co-glycolide) microparticles were well dispersed I could.

In addition, in Fig. 3 (C) and (D), the porosity of the poly (D, L-lactide-co-glycolide) Thus, by closing the pores of the outer surface, sustained releasing of the embedded protein is possible, and the protein activity and protein structure that are embedded for a long time are maintained without denaturation.

In one specific embodiment of the present invention, fluorescein isothiocyanate-dextran (FITC-dextran) was first incorporated into porous poly (D, L-lactide-co-glycolide) microparticles. The porous poly (D, L-lactide-co-glycolide) microparticles before treatment with the solvent mixture had low fluorescence, because physically the phosphor isothiocyanate dextran was adsorbed on the surface and microparticles to be. In contrast, in the poly (D, L-lactide-co-glycolide) microparticles treated with the solvent mixture, a large amount of phosphor isothiocyanate dextran was observed (FIG.

In addition, the fluorescence sensitivity of the solvent-treated poly (D, L-lactide-co-glycolide) microparticles is much higher than that of the solventless poly (D, L-lactide-co- glycolide) microparticles (D, L-lactide-co-glycolide) microparticles containing a large amount of phosphor isothiocyanate dextran (FIG. 4 (B)).

In a specific embodiment of the present invention, albumin from bovine serum (BSA), widely used as a protein for inclusion in poly (D, L-lactide-co-glycolide) microparticles, When used, it was confirmed that there was no denaturation of bovine serum albumin through circular dichroism (CD) spectroscopy of bovine serum albumin and released bovine serum albumin embedded in microparticles. The incorporation rate of bovine serum albumin embedded in the solvent-treated poly (D, L-lactide-co-glycolide) microparticles was 89.7%, and the incorporation rate of poly (D, L-lactide- co- glycolide) The penetration rate for microparticles was much higher than 52.3%.

In addition, the amount of bovine serum albumin released from the untreated poly (D, L-lactide-co-glycolide) microparticles was about 50% on day 1 and released after 10 days, One poly (D, L-lactide-co-glycolide) microparticle was found to release slowly over a period of 60 days without initial overdose release. This can be increased by incorporating high levels of BSA into the protein content and release period. Therefore, it was concluded that the content of protein and the release period could be increased by incorporating a high concentration of bovine serum albumin.

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.

< Example  1> Porous poly (D, L- Lactide -nose- Glycolide ) (Poly (D, L- lactide - co -glycolide) Microparticle production

To prepare microparticles of porous poly (D, L-lactide-co-glycolide), lactide 75: glycolide 25, Sigma-Aldrich) Spraying process was used. 5, 7, 10 and 15% by weight of a solution of poly (D, L-lactide-co-glycolide) dissolved in dimethyl sulfoxide (DMSO) were placed in an aluminum foil collector plate syringe pump (NE-1000, New Era Pump Systems Inc.) at a flow rate of 0.02 mL / min. The distance between the nozzle (24G needle) and the aluminum foil collector plate was 20 cm and a voltage of 15 kV was applied. After evaporation of the solvent, the porous poly (D, L-lactide-co-glycolide) microparticles collected in an aluminum foil were dissolved in phosphate buffered saline (PBS, pH 7.4, Sigma-Aldrich) And lyophilized.

To observe the morphology of the prepared porous poly (D, L-lactide-co-glycolide) microparticles, a scanning electron microscope (SEM, S-4800, Hitachi High- ) Were used.

As a result, a spherical shape was observed when the poly (D, L-lactide-co-glycolide) concentration was 7% or less, and 10% (D, L-lactide-co-glycolide) concentration increases the porosity structure because the solvent evaporates rapidly through the electrospray When making poly (D, L-lactide-co-glycolide) microparticles, the poly (D, L-lactide-co-glycolide) concentration of 5 wt% As shown in Figure 2 (B), the average size of the microparticles was found to increase with increasing concentration of the poly (D, L-lactide-co-glycolide) polymer (D, L-lactide-co-glycolide) microparticles increased from 2.90 ± 0.72 μm to 6.23 ± 1.13 μm. Showed a relatively uniform size with a coefficient of variation of 9.6% when the poly (D, L-lactide-co-glycolide) polymer concentration was 7 wt%.

In conclusion, considering the porosity, physical properties and uniform size of the poly (D, L-lactide-co-glycolide) microparticles, the poly (D, L-lactide-co- glycolide ) (Poly (D, L-lactide-co-glycolide) microparticles concentration of 7 wt.

The room temperature at which the electrospray was performed was 26 ° C., which was higher than the melting point (19 ° C.) of dimethylsulfoxide. Therefore, in forming the porosity of poly (D, L-lactide-co- glycolide) microparticles, The crystallization of the side-solution did not affect the formation of voids in the poly (D, L-lactide-co-glycolide) microparticles, which was accomplished by phase separation of the solvent with evaporation of the solvent during electrospinning Respectively.

< Example  Protein incorporation into poly (D, L-lactide-co-glycolide) microparticles of porous poly (D, L-lactide-co-glycolide)

The microparticles of poly (D, L-lactide-co-glycolide) (poly (D, L-lactide-co- glycolide) microparticles were suspended in 40 mg / mL bovine serum albumin (BSA, Sigma-Aldrich) After immersing in 5 mL phosphate-buffered saline (PBS, pH 7.4), the bovine serum albumin solution was poured through a porous poly (D, L-lactide-co-glycolide) The supernatant from the microparticles was removed using a pipette by centrifugation in the presence of the bovine serum albumin solution in the porous poly (D, L-lactide-co-glycolide) microparticles, 5 mL of an aqueous solution containing dimethyl sulfoxide (DMSO) (20 w / w%) was added. The following mixture was reacted in an orbital shaker for about 4 hours to prepare a porous poly (D, L-lactide - co-glycolide) surface pores of microparticles (D, L-lactide-co-glycolide) microparticles having pores on the surface through a filter paper were obtained and the remaining dimethylsulfoxide solvent was removed, The reason for lyophilization is that it is known that the solid state of protein is more stable than that of aqueous solution.

Then, in order to confirm that the protein is embedded, the fluorescein isothiocyanate-dextran (FITC-dextran, Sigma-Aldrich) was dissolved in poly (D, L-lactide-co- glycolide ) Microparticles.

< Example  3> Analysis of porous poly (D, L-lactide-co-glycolide) microparticles through scanning electron microscopy

A scanning electron microscope (SEM) was used to observe the morphology of the porous poly (D, L-lactide-co-glycolide) microparticles before and after the surface treatment. Free microtome (Cryotome FSE, Thermo scientific, Co. Ltd., USA) was used to observe the cross section of the poly (D, L-lactide-co-glycolide) microparticles by scanning electron microscopy porous poly (D, L- lactide-co-glycolide), average size of the microparticles is image J software (ImageJ software, National Institutes of Health, USA) using (n = 500) measured with a scanning electron microphotograph Respectively.

As a result, the cut surfaces of the particles before and after the 7-wt% surface pores of the porous poly (D, L-lactide-co-glycolide) microparticles were blocked with the dimethylsulfoxide solvent as shown in Fig. The size of the surface pores of the poly (D, L-lactide-co-glycolide) microparticles was 62.7 ± 8.5 nm and the inner pores were confirmed to be larger than the surface pores. A mixture of phosphate-buffered saline (PBS) and dimethyl sulfoxide (DMSO) was used to close the microporous surface pores. When the ratio of dimethyl sulfoxide was higher than 30 w / w%, a large lump was formed due to the tendency of the porous poly (D, L-lactide-co-glycolide) microparticles to join with each other.

Therefore, the mixing ratio of the dimethylsulfoxide and the phosphate buffered saline solution was maintained at 20 w / w%, and it was confirmed that the porosity of the inside was maintained even when the holes on the surface were lost as shown in (C) and (D)

In order to confirm whether fluorescein isothiocyanate-dextran (FITC-dextran, Sigma-Aldrich) remained in the poly (D, L-lactide-co-glycolide) microparticles, a confocal microscope (LSM700, ZEISS, Germany). Fluorescence sensitivity and distribution of fluorescent isothiocyanate dextran contained in poly (D, L-lactide-co-glycolide) microparticles through image J software and confocal microscope photographs are summarized. To measure the degree of protein denaturation, albumin from bovine serum (BSA) protein treated with 0, 20, and 50 w / w% dimethyl sulfoxide (DMSO) solution for 4 hours was subjected to circular polarization dichroism The degree of denaturation of the protein with respect to the dimethylsulfoxide aqueous solution was observed using a circular dichroism spectroscope (J-815, Jasco International, Co. Ltd., Japan).

In order to confirm the incorporation of the protein, the phosphor isothiocyanate dextran was incorporated into the porous poly (D, L-lactide-co-glycolide) microparticles in the same manner as in Example 2.

As a result, the porous poly (D, L-lactide-co-glycolide) microparticles had low fluorescence before being treated with the solvent mixture as shown in FIG. 4 (A) L-lactide-co-glycolide) microparticles, a large amount of phosphor isothiocyanate dextran was observed.

The fluorescence sensitivities of the poly (D, L-lactide-co-glycolide) microparticles containing the phosphor isothiocyanate dextran before and after the solvent treatment were quantitatively analyzed. As a result, The fluorescence sensitivity of the poly (D, L-lactide-co-glycolide) microparticles treated was much higher than that of the poly (D, L-lactide-co- glycolide) , Suggesting that a large amount of phosphorus isothiocyanate dextran was incorporated into the solvent-treated poly (D, L-lactide-co-glycolide) microparticles.

< Example  4> Poly (D, L- Lactide -nose- Glycolide ) ( Poly (D, L- lactide - co - glycolide ) Analysis of denaturation of proteins embedded in microparticles

Since protein denaturation is crucial for the incorporation of proteins into the transporter, circular dichroism (CD) spectroscopy can be used to determine whether protein denaturation occurs by dimethyl sulfoxide (DMSO) Respectively.

As shown in FIG. 5 (A), denaturation of bovine serum albumin (BSA) was confirmed by alpha -hellix fingerprint in the 208 and 222 nm circular dichroism spectra. As a result, , And there was no difference in the circular dichroism spectrum of the bovine serum albumin exposed to the mixture of the 50% w / w dimethylsulfoxide and the bovine serum albumin embedded in the microparticles and the bovine serum albumin It was also confirmed that there was no denaturation of bovine serum albumin even in the circular dichroism spectrum.

< Example  5> Analysis of protein incorporation efficiency into poly (D, L-lactide-co-glycolide) microparticles

In order to investigate the efficiency of the incorporation of bovine serum albumin (BSA) into poly (D, L-lactide-co-glycolide) 10 mg of poly (D, L-lactide-co-glycolide) microparticles containing dried bovine serum albumin were dissolved in 1 mL of dimethylchloride (DCM), and then 10 mL of phosphate- buffered saline, PBS, pH 7.4), and the mixture was stirred for 1 hour to elute bovine serum albumin. Then, the mixture was centrifuged at 3000 rpm for 5 minutes to induce phase separation of water and organic solvent. (Bio-Rad Protein Assay reagent (Cat. # 500-0006, Bio-Rad Laboratories Inc.) was used to measure the concentration of bovine serum albumin eluted in the culture medium. 10 mL of the solution and 200 mL of the protein assay solution The absorbance of the mixed solution was measured at 595 nm using a microplate spectrophotometer (EON, BioTek, USA). The penetration efficiency was calculated by subtracting the actual amount of bovine serum albumin (D, L-lactide-co-glycolide) microparticles containing bovine serum albumin (10 mg / mL) were dissolved in phosphate buffered saline (PBS) to determine drug release behavior. The amount of bovine serum albumin released was measured at a fixed time with an absorbance of 595 nm using a microplate spectrophotometer All experiments were repeated three times and the results were as follows: ± standard deviations.

The incorporation rate of bovine serum albumin embedded in the solvent-treated poly (D, L-lactide-co-glycolide) microparticles was 89.7%, and the incorporation rate of poly (D, L-lactide- co- glycolide) Which was significantly higher than the 52.3% incorporation of bovine serum albumin into microparticles.

As shown in Fig. 5 (B), the amount of bovine serum albumin released from poly (D, L-lactide-co-glycolide) (D, L-lactide-co-glycolide) microparticles were found to have release stabilizers at about 50% at day 1 and after 10 days in contrast to solvent-treated poly It was confirmed that the long - term sustained release of bovine serum albumin. Thus, it was considered that the content of protein and the release period could be increased by incorporating bovine serum albumin at a high concentration.

Claims (9)

Preparing a spraying stock solution containing the polymer;
Spraying the prepared spraying stock solution while applying a voltage to produce porous polymer microparticles;
Applying a vacuum to the porous polymeric microparticles to incorporate the drug; And
The surface of the porous polymer microparticles is dissolved by immersing the drug-containing porous polymer microparticles in a dimethylsulfoxide aqueous solution containing 1 to 30 wt% based on the total weight of the saline solution for 1 to 4 hours, Closing the hole in the particle surface;
Wherein the porous polymer microparticles are produced by a method comprising the steps of: The method for producing porous polymer microparticles according to claim 1, wherein the polymer has biodegradability and biocompatibility. The method of claim 2, wherein the biodegradable and biocompatible polymer is selected from the group consisting of poly (D, L-lactide-co-glycolide) (Poly (D, L- lactide-co-glycolide, PLGA) and Polycaprolactone (PCL). The method of claim 1, wherein the spraying liquid containing the polymer has a concentration of 1 to 20 wt%. 5. The method of claim 4, wherein the spraying liquid comprises an organic solvent having a high volatility point. The porous polymer microparticle of claim 5, wherein the organic solvent having a high volatility point is selected from the group consisting of dimethyl sulfoxide (DMSO), acetonitrile, and dimethyl carbonate. Gt; The method of claim 1, wherein the step of forming the porous polymer microparticles is performed while the voltage is applied in a range of 10 to 20 kV. The method of claim 1, wherein the drug is selected from the group consisting of a protein, a peptide, a hydrophobic drug, a hydrophilic drug, or a poorly soluble drug. 9. A porous polymer microparticle produced by the production method according to any one of claims 1 to 8.

Images