Hydrophilic core-shell polylactic acid microspheres as well as preparation method and application thereof

Abstract

The invention provides a hydrophilic core-shell polylactic acid microsphere as well as a preparation method and application thereof, and belongs to the technical field of polylactic acid microspheres. The preparation method comprises the following steps: mixing polylactic acid with an organic solvent to obtain an oil phase, then mixing the oil phase with a surfactant solution for emulsification, controlling the emulsification rate to obtain polylactic acid microspheres with uniform particle sizes, and then mixing the polylactic acid microspheres with a modifier solution to obtain the hydrophilic core-shell polylactic acid microspheres. By controlling the variety of the modifier, the hydrophilicity, stability and reaction activity of the polylactic acid microspheres are improved, a silane coupling agent or an initiator does not need to be used in the preparation process, and the preparation method is safe and non-toxic.

Description

Technical Field

[0001] The invention belongs to the technical field of polylactic acid microspheres, and in particular relates to core-shell polylactic acid microspheres and a preparation method and application thereof. Background Art

[0002] Microspheres usually refer to tiny spherical entities formed by drugs dissolved or dispersed in a polymer matrix. They are matrix-type skeleton particles with a particle size generally between 1 and 250 μm. Polylactic acid (PLA) is widely used in the biomedical field due to its good biocompatibility and biodegradability.

[0003] Core-shell polylactic acid microspheres are based on polylactic acid as the core, and the shell has good biological activity and unique affinity for specific tissue environments, which makes the polylactic acid microspheres have higher biocompatibility and maintain a certain stability. The lack of hydrophilic groups in the structure of polylactic acid leads to strong hydrophobicity on the surface of the material, resulting in poor hydrophilicity, which affects its compatibility with biological tissues and the loading and release of bioactive molecules. In the prior art, silane coupling agents or free radical polymerization initiators are usually used to modify the surface of polylactic acid microspheres when preparing core-shell polylactic acid microspheres, but toxic reagents are inevitably introduced during the modification process, thereby limiting its application in the field of biomedicine.

[0004] Therefore, there is an urgent need for a method for preparing safe and nontoxic hydrophilic core-shell polylactic acid microspheres. Summary of the invention

[0005] The purpose of the present invention is to provide a hydrophilic core-shell polylactic acid microsphere and its preparation method and application. The preparation method provided by the present invention is safe and non-toxic, and the prepared core-shell polylactic acid microsphere has uniform and controllable particle size and has excellent hydrophilicity, stability and reactivity.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing hydrophilic core-shell polylactic acid microspheres, comprising the following steps:

[0008] (1) mixing polylactic acid and an organic solvent to obtain an oil phase;

[0009] (2) mixing the oil phase obtained in step (1) with a surfactant solution and emulsifying the mixture to obtain polylactic acid microspheres; the emulsification rate is 2000 to 10000 rpm;

[0010] (3) mixing the polylactic acid microspheres obtained in step (2) with a modifier solution and then drying to obtain hydrophilic core-shell polylactic acid microspheres; the modifier comprises at least one of sodium carboxymethyl cellulose, sodium hyaluronate, hydroxypropyl methylcellulose and amino acids.

[0011] Preferably, the concentration of polylactic acid in the oil phase in step (1) is 5 to 40 g / L.

[0012] Preferably, the mass concentration of the surfactant solution in step (2) is 0.25-2%.

[0013] Preferably, in step (2), the volume ratio of the oil phase to the surfactant solution is 1:(5-40).

[0014] Preferably, the mixing in step (2) is performed by injecting the oil phase into the surfactant solution using a microfluidic device.

[0015] Preferably, the emulsification temperature in step (2) is 20 to 30° C., and the emulsification time is 10 to 30 minutes.

[0016] Preferably, the mass concentration of the modifier solution in step (3) is 0.1-2%.

[0017] Preferably, the mixing temperature in step (3) is 20 to 30° C., and the mixing time is 10 to 15 hours.

[0018] The present invention also provides hydrophilic core-shell polylactic acid microspheres prepared by the preparation method described in the above technical solution, comprising a polylactic acid core and a modifier shell wrapped on the surface of the polylactic acid core.

[0019] The present invention also provides the application of the hydrophilic core-shell polylactic acid microspheres described in the above technical solution in the field of biomedicine.

[0020] The present invention provides a method for preparing hydrophilic core-shell polylactic acid microspheres, comprising the following steps:

[0021] (1) polylactic acid and an organic solvent are mixed to obtain an oil phase; (2) the oil phase obtained in the step (1) is mixed with a surfactant solution and emulsified to obtain polylactic acid microspheres; the emulsification rate is 2000-10000 rpm; (3) the polylactic acid microspheres obtained in the step (2) are mixed with a modifier solution and then dried to obtain hydrophilic core-shell polylactic acid microspheres; the modifier includes at least one of sodium carboxymethyl cellulose, sodium hyaluronate, hydroxypropyl methylcellulose and amino acids. The present invention mixes polylactic acid and an organic solvent to obtain an oil phase, then mixes the oil phase with a surfactant solution for emulsification, controls the emulsification rate, obtains polylactic acid microspheres with uniform particle size, then mixes the oil phase with a modifier solution to obtain hydrophilic core-shell polylactic acid microspheres, controls the type of modifier, improves the hydrophilicity, stability and reactivity of the polylactic acid microspheres, and does not require the use of silane coupling agents or initiators during the preparation process, which is safe and non-toxic. The results of the examples show that the hydrophilic core-shell polylactic acid microspheres prepared by the present invention have uniform particle size distribution, similar sizes, perfect sphericity, no impurities on the surface, and excellent stability and hydrophilicity. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a SEM image of the hydrophilic core-shell polylactic acid microspheres prepared in Example 1 of the present invention;

[0023] Figure 2 This is a FIB-SEM image of the hydrophilic core-shell polylactic acid microspheres prepared in Example 1 of the present invention;

[0024] Figure 3 This is a particle size distribution diagram of the hydrophilic core-shell polylactic acid microspheres prepared in Example 1 of the present invention;

[0025] Figure 4 This is a SEM image of the hydrophilic core-shell polylactic acid microspheres prepared in Example 2 of the present invention;

[0026] Figure 5 This is an optical microscope image of the hydrophilic core-shell polylactic acid microspheres prepared in Example 3 of the present invention;

[0027] Figure 6 This is an optical microscope image of the polylactic acid microspheres prepared in Comparative Example 1;

[0028] Figure 7 The water contact angle of the polylactic acid microspheres prepared in Comparative Example 1;

[0029] Figure 8 This is the water contact angle of the hydrophilic core-shell polylactic acid microspheres prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0030] The present invention provides a method for preparing hydrophilic core-shell polylactic acid microspheres, comprising the following steps:

[0031] (1) mixing polylactic acid and an organic solvent to obtain an oil phase;

[0032] (2) mixing the oil phase obtained in step (1) with a surfactant solution and emulsifying the mixture to obtain polylactic acid microspheres; the emulsification rate is 2000 to 10000 rpm;

[0033] (3) mixing the polylactic acid microspheres obtained in step (2) with a modifier solution and then drying to obtain hydrophilic core-shell polylactic acid microspheres; the modifier comprises at least one of sodium carboxymethyl cellulose, sodium hyaluronate, hydroxypropyl methylcellulose and amino acids.

[0034] Unless otherwise specified, the present invention has no particular limitation on the sources of the raw materials, and commercially available products known to those skilled in the art may be used.

[0035] The invention mixes polylactic acid and an organic solvent to obtain an oil phase.

[0036] In the present invention, the molecular weight (M w ) is preferably 70000 to 90000, and more preferably 80000. In the present invention, the molecular weight of polylactic acid is controlled within the above range, which can further improve the particle size uniformity of the core-shell polylactic acid microspheres.

[0037] In the present invention, the organic solvent preferably includes at least one of dichloromethane, chloroform, tetrahydrofuran, ethyl acetate, ethanol, dimethyl sulfoxide and acetone.

[0038] In the present invention, the concentration of polylactic acid in the oil phase is preferably 5 to 40 g / L. In an embodiment of the present invention, the concentration of polylactic acid in the oil phase may be specifically 5 g / L, 10 g / L, 15 g / L, 20 g / L, 25 g / L, 30 g / L, 35 g / L or 40 g / L. The present invention limits the concentration of polylactic acid in the oil phase to the above range, so that polylactic acid can be fully dissolved.

[0039] The present invention has no special limitation on the mixing operation of the polylactic acid and the organic solvent. The two can be evenly mixed using a material mixing technical solution well known to those skilled in the art.

[0040] After obtaining the oil phase, the present invention mixes the oil phase with a surfactant solution for emulsification to obtain polylactic acid microspheres.

[0041] In the present invention, the surfactant is preferably polyvinyl alcohol; the alcoholysis degree of the polyvinyl alcohol is preferably 98-99% (mol / mol).

[0042] In the present invention, the solvent in the surfactant solution is preferably deionized water.

[0043] In the present invention, the mass concentration of the surfactant solution is preferably 0.25-2%. In an embodiment of the present invention, the mass concentration of the surfactant solution can be specifically 0.25%, 0.5%, 1%, 1.5% or 2%. The present invention limits the mass concentration of the surfactant solution to the above range, so that the surfactant can be fully dissolved.

[0044] In the present invention, the volume ratio of the oil phase to the surfactant solution is preferably 1:(5-40). In an embodiment of the present invention, the volume ratio of the oil phase to the surfactant solution may specifically be 1:5, 1:10, 1:15, 1:20, 1:25, 1:30, 1:35 or 1:40. The present invention limits the volume ratio of the oil phase to the surfactant solution within the above range, and can obtain polylactic acid microspheres with uniform particle size distribution, similar size and perfect sphericity.

[0045] In the present invention, the mixing of the oil phase and the surfactant solution is preferably performed by injecting the oil phase into the surfactant solution using a microfluidic device, more preferably injecting the oil phase into the uniformly emulsified surfactant solution using a microfluidic device.

[0046] In the present invention, the microchannel size of the microfluidic device is preferably 0.6-0.8 mm, more preferably 0.7 mm; the injection rate of the microfluidic device is preferably 2.5-25 mL / min. In an embodiment of the present invention, the injection rate of the microfluidic device can be specifically 2.5 mL / min, 5 mL / min, 10 mL / min, 15 mL / min, 20 mL / min or 25 mL / min. The present invention controls the mixing method and parameters, which is more conducive to obtaining polylactic acid microspheres with uniform particle size and perfect sphericity.

[0047] In the present invention, the emulsification rate is 2000-10000rpm. In an embodiment of the present invention, the emulsification rate can be specifically 2000rpm, 3000rpm, 4000rpm, 5000rpm, 6000rpm, 7000rpm, 8000rpm, 9000rpm or 10000rpm. The present invention limits the emulsification rate within the above range, which can fully emulsify the oil phase and is more conducive to obtaining polylactic acid microspheres with uniform particle size and perfect sphericity.

[0048] In the present invention, the emulsification temperature is preferably 20-30°C; the emulsification time is preferably 10-30 minutes. In the present invention, the emulsification time is calculated from the completion of the injection of the oil phase. In an embodiment of the present invention, the emulsification time may be specifically 10 minutes, 15 minutes, 20 minutes, 25 minutes or 30 minutes. The present invention limits the emulsification temperature and time within the above range, which can make the emulsification more complete.

[0049] After obtaining the polylactic acid microspheres, the present invention mixes the polylactic acid microspheres with a modifier solution and then dries the mixture to obtain hydrophilic core-shell polylactic acid microspheres.

[0050] In the present invention, the modifier includes at least one of sodium carboxymethylcellulose, sodium hyaluronate, hydroxypropyl methylcellulose and amino acid, preferably sodium carboxymethylcellulose. The present invention uses the modifier to modify the surface of the polylactic acid microspheres, providing rich functional groups, thereby improving the hydrophilicity and stability of the polylactic acid microspheres.

[0051] In the present invention, the solvent in the modifier solution is preferably deionized water.

[0052] In the present invention, the modifier solution also preferably includes an active factor; the active factor preferably includes at least one of collagen and regenerated protein. The active factor is added to the prepared core-shell polylactic acid microspheres to load the active factor, which has better biomedical applications.

[0053] In the present invention, the mass concentration of the modifier solution is preferably 0.1-2%. In an embodiment of the present invention, the mass concentration of the modifier solution can be specifically 0.1%, 0.5%, 1%, 1.5% or 2%. The present invention limits the mass concentration of the modifier solution to the above range, so that the modifier can be fully dissolved.

[0054] In the present invention, the mass ratio of the polylactic acid microspheres to the modifier solution is preferably (3-5):100, more preferably 4:100.

[0055] In the present invention, the mixing temperature is preferably 20-30°C; the mixing time is preferably 10-15h, more preferably 12-15h; the mixing is preferably carried out under stirring; the stirring rate is preferably 200-600rpm, more preferably 400-500rpm. In the present invention, during the mixing process, the organic solvent gradually evaporates, and the modifier is wrapped on the surface of the polylactic acid microspheres to form hydrophilic core-shell polylactic acid microspheres.

[0056] After the mixing is completed, the present invention preferably washes the mixed product with water. The present invention has no special limitation on the operation of the water washing, and the water washing technical solution well known to those skilled in the art can be used.

[0057] In the present invention, the drying preferably comprises liquid nitrogen quick freezing and freeze drying performed sequentially.

[0058] The present invention has no particular limitation on the time of liquid nitrogen quick freezing, and a technical solution well known to those skilled in the art may be adopted.

[0059] In the present invention, the freeze-drying temperature is preferably -20 to -80°C, more preferably -20 to -60°C; the freeze-drying time is preferably 10 to 15 hours.

[0060] The preparation method provided by the invention is safe and non-toxic. The prepared hydrophilic core-shell polylactic acid microspheres have uniform particle size distribution, similar sizes, perfect sphericity, no surface impurities, and high ball formation rate. Moreover, by controlling the amount, concentration and other parameters of each raw material, the particle size of the hydrophilic core-shell polylactic acid microspheres can be controlled.

[0061] The present invention also provides hydrophilic core-shell polylactic acid microspheres prepared by the preparation method described in the above technical solution.

[0062] In the present invention, the hydrophilic core-shell polylactic acid microspheres have polylactic acid as the core and a modifier as the shell.

[0063] The hydrophilic core-shell polylactic acid microspheres prepared by the invention have uniform particle size distribution, similar size, perfect sphericity, no impurities on the surface, and the average particle size is preferably 10-150 μm.

[0064] The present invention also provides the application of the hydrophilic core-shell polylactic acid microspheres described in the above technical solution in the field of biomedicine.

[0065] The present invention has no special limitation on the operation of the application, and the technical solutions of the application well known to those skilled in the art may be adopted.

[0066] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0067] Example 1

[0068] The preparation method of hydrophilic core-shell polylactic acid microspheres is as follows:

[0069] (1) 400 mg of polylactic acid (Mw =80000) was dissolved in 20 mL of dichloromethane to obtain an oil phase with a concentration of 20 g / L;

[0070] (2) dissolving polyvinyl alcohol (McLean, model P815725, alcoholysis degree 98-99% (mol / mol)) in 100 mL of deionized water at 90° C. to obtain a surfactant solution with a mass concentration of 1%;

[0071] (3) adjusting the emulsification rate of the emulsifier to 5000 rpm, injecting 2 mL of the oil phase in step (1) into 50 mL of the surfactant solution in step (2) through a microfluidic device, and emulsifying at room temperature for 20 min to obtain polylactic acid microspheres, wherein the microchannel size of the microfluidic device is 0.7 mm, the injection rate is 20 mL / min, and the volume ratio of the oil phase to the surfactant solution is 1:25;

[0072] (4) Pour the polylactic acid microspheres obtained in step (3) into a sodium carboxymethyl cellulose aqueous solution (mass concentration is 0.8%, and the volume ratio of polylactic acid microspheres to sodium carboxymethyl cellulose aqueous solution is 4:100), stir at 500 rpm for 12 hours, and completely volatilize the dichloromethane. After washing with water and quick freezing with liquid nitrogen, place the microspheres in a freeze dryer at -50°C and freeze-dry for 12 hours to obtain hydrophilic core-shell polylactic acid microspheres.

[0073] The SEM image of the hydrophilic core-shell polylactic acid microspheres prepared in Example 1 is as follows: Figure 1 As shown, the FIB-SEM image is Figure 2 The particle size distribution diagram is shown in Figure 3 As shown. Figures 1 to 3 It can be seen that the hydrophilic core-shell polylactic acid microspheres prepared in Example 1 have uniform particle size distribution, similar size, no agglomeration, perfect sphericity, no impurities on the surface, and an average particle size of 10.325 μm.

[0074] Example 2

[0075] The preparation method of hydrophilic core-shell polylactic acid microspheres is as follows:

[0076] (1) 200 mg of polylactic acid (M w =80000) was dissolved in 20 mL of dichloromethane to obtain an oil phase with a concentration of 10 g / L;

[0077] (2) dissolving polyvinyl alcohol (McLean, model P815725, alcoholysis degree 98-99% (mol / mol)) in 100 mL of deionized water at 90° C. to obtain a surfactant solution with a mass concentration of 1%;

[0078] (3) adjusting the emulsification rate of the emulsifier to 5000 rpm, injecting 2.5 mL of the oil phase in step (1) into 30 mL of the surfactant solution in step (2) through a microfluidic device, and emulsifying at room temperature for 10 min to obtain polylactic acid microspheres, wherein the microchannel size of the microfluidic device is 0.7 mm, the injection rate is 20 mL / min, and the volume ratio of the oil phase to the surfactant solution is 1:12;

[0079] (4) Pour the polylactic acid microspheres obtained in step (3) into a sodium carboxymethyl cellulose aqueous solution (mass concentration is 0.75%, and the volume ratio of polylactic acid microspheres to sodium carboxymethyl cellulose aqueous solution is 4:100), stir at 500 rpm for 12 hours, and completely volatilize the dichloromethane. After washing with water and quick freezing with liquid nitrogen, place the microspheres in a freeze dryer at -50°C and freeze-dry for 12 hours to obtain hydrophilic core-shell polylactic acid microspheres.

[0080] The SEM image of the hydrophilic core-shell polylactic acid microspheres prepared in Example 2 is as follows: Figure 4 As shown. Figure 4 It can be seen that the hydrophilic core-shell polylactic acid microspheres prepared in Example 2 have uniform particle size distribution, similar size, no agglomeration, perfect sphericity, no impurities on the surface, and an average particle size of 13.325 μm.

[0081] Example 3

[0082] The preparation method of hydrophilic core-shell polylactic acid microspheres is as follows:

[0083] (1) 300 mg of polylactic acid (M w =80000) was dissolved in 20 mL of dichloromethane to obtain an oil phase with a concentration of 15 g / L;

[0084] (2) dissolving polyvinyl alcohol (McLean, model P815725, alcoholysis degree 98-99% (mol / mol)) in 100 mL of deionized water at 90° C. to obtain a surfactant solution with a mass concentration of 1%;

[0085] (3) adjusting the emulsification rate of the emulsifier to 5000 rpm, injecting 2 mL of the oil phase in step (1) into 80 mL of the surfactant solution in step (2) through a microfluidic device, and emulsifying at room temperature for 15 min to obtain polylactic acid microspheres, wherein the microchannel size of the microfluidic device is 0.7 mm, the injection rate is 20 mL / min, and the volume ratio of the oil phase to the surfactant solution is 1:40;

[0086] (4) Pour the polylactic acid microspheres obtained in step (3) into a sodium carboxymethyl cellulose aqueous solution (mass concentration is 1%, and the volume ratio of polylactic acid microspheres to sodium carboxymethyl cellulose aqueous solution is 4:100), stir at 500 rpm for 12 hours, and completely volatilize the dichloromethane. After washing with water and quick freezing with liquid nitrogen, place the microspheres in a freeze dryer at -50°C and freeze-dry for 12 hours to obtain hydrophilic core-shell polylactic acid microspheres.

[0087] The optical microscope image of the hydrophilic core-shell polylactic acid microspheres prepared in Example 3 is as follows: Figure 5 As shown. Figure 5 It can be seen that the hydrophilic core-shell polylactic acid microspheres prepared in Example 3 have uniform particle size distribution, similar size, no agglomeration, perfect sphericity, no impurities on the surface, and an average particle size of 13.874 μm.

[0088] Example 4

[0089] The preparation method of hydrophilic core-shell polylactic acid microspheres is as follows:

[0090] (1) 400 mg of polylactic acid (M w =80000) was dissolved in 20 mL of dichloromethane to obtain an oil phase with a concentration of 20 g / L;

[0091] (2) dissolving polyvinyl alcohol (McLean, model P815725, alcoholysis degree 98-99% (mol / mol)) in 100 mL of deionized water at 90° C. to obtain a surfactant solution with a mass concentration of 0.8%;

[0092] (3) adjusting the emulsification rate of the emulsifier to 7000 rpm, injecting 2 mL of the oil phase in step (1) into 50 mL of the surfactant solution in step (2) through a microfluidic device, and emulsifying at room temperature for 15 min to obtain polylactic acid microspheres, wherein the microchannel size of the microfluidic device is 0.7 mm, the injection rate is 25 mL / min, and the volume ratio of the oil phase to the surfactant solution is 1:25;

[0093] (4) Pour the polylactic acid microspheres obtained in step (3) into a sodium carboxymethyl cellulose aqueous solution (mass concentration is 1%, and the volume ratio of polylactic acid microspheres to sodium carboxymethyl cellulose aqueous solution is 4:100), stir at 500 rpm for 12 hours, and completely volatilize the dichloromethane. After washing with water and quick freezing with liquid nitrogen, place the microspheres in a freeze dryer at -50°C and freeze-dry for 12 hours to obtain hydrophilic core-shell polylactic acid microspheres.

[0094] The hydrophilic core-shell polylactic acid microspheres prepared in Example 4 have uniform particle size distribution, similar size, no agglomeration, perfect sphericity, no impurities on the surface, high ball formation rate, and an average particle size of 12.413 μm.

[0095] Example 5

[0096] The preparation method of hydrophilic core-shell polylactic acid microspheres is as follows:

[0097] (1) 400 mg of polylactic acid (M w =80000) was dissolved in 20 mL of dichloromethane to obtain an oil phase with a concentration of 20 g / L;

[0098] (2) dissolving polyvinyl alcohol (McLean, model P815725, alcoholysis degree 98-99% (mol / mol)) in 100 mL of deionized water at 90° C. to obtain a surfactant solution with a mass concentration of 0.8%;

[0099] (3) adjusting the emulsification rate of the emulsifier to 7000 rpm, injecting 2 mL of the oil phase in step (1) into 80 mL of the surfactant solution in step (2) through a microfluidic device, and emulsifying at room temperature for 20 min to obtain polylactic acid microspheres, wherein the microchannel size of the microfluidic device is 0.7 mm, the injection rate is 25 mL / min, and the volume ratio of the oil phase to the surfactant solution is 1:40;

[0100] (4) Pour the polylactic acid microspheres obtained in step (3) into a sodium carboxymethyl cellulose aqueous solution (mass concentration is 1%, and the volume ratio of polylactic acid microspheres to sodium carboxymethyl cellulose aqueous solution is 4:100), stir at 500 rpm for 12 hours, and completely volatilize the dichloromethane. After washing with water and quick freezing with liquid nitrogen, place the microspheres in a freeze dryer at -50°C and freeze-dry for 12 hours to obtain hydrophilic core-shell polylactic acid microspheres.

[0101] The hydrophilic core-shell polylactic acid microspheres prepared in Example 5 have uniform particle size distribution, similar size, no agglomeration, perfect sphericity, no impurities on the surface, high ball formation rate, and an average particle size of 11.325 μm.

[0102] Comparative Example 1

[0103] (1) 400 mg of polylactic acid (M w =80000) was dissolved in 20 mL of dichloromethane to obtain an oil phase with a concentration of 20 g / L;

[0104] (2) dissolving polyvinyl alcohol (McLean, model P815725, alcoholysis degree 98-99% (mol / mol)) in 100 mL of deionized water at 90° C. to obtain a surfactant solution with a mass concentration of 1%;

[0105] (3) The emulsifying rate of the emulsifier is adjusted to 1000 rpm, and 2 mL of the oil phase in step (1) is injected into 50 mL of the surfactant solution in step (2) through a microfluidic device, and emulsified at room temperature for 20 min to obtain polylactic acid microspheres. The microchannel size of the microfluidic device is 0.7 mm, the injection rate is 20 mL / min, and the volume ratio of the oil phase to the surfactant solution is 1:25 to obtain polylactic acid microspheres.

[0106] The optical microscope image of the polylactic acid microspheres prepared in Comparative Example 1 is as follows: Figure 6 As shown. Figure 6 It can be seen that the polylactic acid microspheres contain huge spherical shadows, which are polylactic acid oil droplets that are not fully emulsified. Therefore, it can be seen that appropriate emulsification power is crucial to the sphering of core-shell polylactic acid microspheres.

[0107] The water contact angle of the polylactic acid microspheres prepared in Comparative Example 1 is as follows: Figure 7 As shown, the water contact angle of the hydrophilic core-shell polylactic acid microspheres prepared in Example 1 is as follows Figure 8 As shown. Figures 7-8 It can be seen that the water contact angle of the polylactic acid microspheres prepared in Comparative Example 1 is 116°, and the water contact angle of the hydrophilic core-shell polylactic acid microspheres prepared in Example 1 is 32.6°. It can be seen that the hydrophilic core-shell polylactic acid microspheres prepared in the present invention have better hydrophilicity and stability.

[0108] In summary, the preparation method provided by the present invention is safe and non-toxic, and the prepared hydrophilic core-shell polylactic acid microspheres have uniform particle size distribution, similar size, perfect sphericity, no impurities on the surface, high ball formation rate, and excellent hydrophilicity and stability.

[0109] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing hydrophilic core-shell polylactic acid microspheres, comprising the following steps: (1) mixing polylactic acid and an organic solvent to obtain an oil phase; (2) mixing the oil phase obtained in step (1) with a surfactant solution and emulsifying the mixture to obtain polylactic acid microspheres; the emulsification rate is 2000 to 10000 rpm; (3) mixing the polylactic acid microspheres obtained in step (2) with a modifier solution and then drying to obtain hydrophilic core-shell polylactic acid microspheres; the modifier comprises at least one of sodium carboxymethyl cellulose, sodium hyaluronate, hydroxypropyl methylcellulose and amino acids.

2. The preparation method according to claim 1, characterized in that: The concentration of polylactic acid in the oil phase in step (1) is 5 to 40 g / L.

3. The preparation method according to claim 1, characterized in that: The mass concentration of the surfactant solution in step (2) is 0.25-2%.

4. The preparation method according to claim 1 or 3, characterized in that: In the step (2), the volume ratio of the oil phase to the surfactant solution is 1:(5-40).

5. The preparation method according to claim 1, characterized in that: The mixing in step (2) is as follows: the oil phase is injected into the surfactant solution using a microfluidic device.

6. The preparation method according to claim 1, characterized in that: The emulsification temperature in step (2) is 20 to 30° C., and the emulsification time is 10 to 30 minutes.

7. The preparation method according to claim 1, characterized in that: The mass concentration of the modifier solution in step (3) is 0.1-2%.

8. The preparation method according to claim 1, characterized in that: The mixing temperature in step (3) is 20 to 30° C., and the mixing time is 10 to 15 hours.

9. The hydrophilic core-shell polylactic acid microspheres prepared by the preparation method according to any one of claims 1 to 8, comprising a polylactic acid core and a modifier shell wrapped on the surface of the polylactic acid core.

10. Use of the hydrophilic core-shell polylactic acid microspheres according to claim 9 in the field of biomedicine.

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