High-drug-loading microgel and preparation method thereof
The high-drug-loading microgels were prepared by microfluidic technology and anti-solvent precipitation mechanism, which solved the problems of low drug loading and unstable release of traditional microgels and achieved efficient and stable drug delivery.
Patent Information
- Application Number
- CN202510805288.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-17
- Publication Date
- 2025-09-12
AI Technical Summary
Traditional microgels have low drug loading and unstable release when encapsulating hydrophobic drugs, which makes it difficult to meet clinical treatment needs.
Microfluidic technology is combined with antisolvent precipitation mechanism to prepare high-drug-loaded microgels by dissolving hydrophobic drugs in organic solvents and rapidly precipitating and crystallizing them in microgels, combined with chemical, photocrosslinking or ionic crosslinking.
The drug loading capacity and drug release stability of the microgel were significantly improved, long-term and stable drug release was achieved, and the application scope of hydrogel materials in the field of drug delivery was expanded.
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Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to a high-drug-loading microgel and a preparation method thereof. Background Art
[0002] Microgels, as a cross-linked polymer network composed of hydrophilic biomaterials such as chitosan, alginate, and gelatin, have been widely used in biomedical fields such as drug delivery and tissue engineering due to their excellent biocompatibility and biodegradability. Their adjustable mechanical properties and structural versatility make them extremely advantageous in in vivo applications. Through chemical modification or surface functionalization, they can also enhance targeting ability, protect bioactive molecules, and regulate immune responses.
[0003] However, the hydrophilic polymer network characteristics of traditional microgels result in significant defects when encapsulating hydrophobic drugs: on the one hand, hydrophobic drugs have extremely low solubility in aqueous solution, making it difficult to effectively dissolve and encapsulate them in the hydrogel system, resulting in low drug loading; on the other hand, even if successfully loaded, the hydrophilic and porous structure of the microgels causes the drug release to mainly follow the dissolution-diffusion mechanism, which is very prone to burst release under physiological conditions, making it impossible to achieve sustained and stable drug release, making it difficult to meet clinical treatment needs.
[0004] Therefore, how to improve the loading capacity of microgels for hydrophobic drugs and optimize their controlled release performance has become a key technical problem that needs to be solved urgently. Summary of the Invention
[0005] The present invention aims to provide a high-drug-loading microgel and its preparation method. This approach addresses the current problem of low drug loading when encapsulating hydrophobic drugs in microgels. By leveraging microfluidics and the antisolvent effect, the hydrophobic drug dissolved in an organic solvent is rapidly precipitated and partially crystallized within the microgel. This method not only significantly increases drug loading but also allows the crystallized drug to be slowly released from the microgel, achieving sustained drug release.
[0006] In order to solve the above technical problems, the technical solutions adopted by the present invention are as follows:
[0007] A method for preparing a high-drug-loaded microgel comprises the following steps:
[0008] S1. Dissolve the hydrophobic drug in an organic solvent as dispersed phase 1; dissolve the polymer material in an aqueous solution as dispersed phase 2; and use the oil phase as the continuous phase;
[0009] S2, injecting the dispersed phase 1, dispersed phase 2 and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump to form droplets;
[0010] S3. Cross-link the droplets obtained in S2 to obtain a high drug loading microgel.
[0011] Preferably, in S1, the mass concentration of the hydrophobic drug in the dispersed phase 1 is 1%-10%, and the hydrophobic drug includes one of ibuprofen (Ibu), fenofibrate (Fen), methylprednisolone (Mps), naproxen (Nap), celecoxib (Cel), dexamethasone (Dex), paclitaxel (Pac), atorvastatin (Ato), itraconazole (Itr), and ritonavir (Rit).
[0012] Preferably, in S1, the organic solvent includes one of dimethyl sulfoxide, acetonitrile, methanol, ethanol, acetone, propylene glycol, isopropanol, ethylene glycol, tetrahydrofuran, N-methylpyrrolidone, and dimethylformamide.
[0013] Preferably, in S1, the mass concentration of the polymer material in the dispersed phase 2 is 1%-10%, and the polymer material includes one of chitosan (CS), polyethylene glycol diacrylate (PEGDA), sodium alginate (SA), gelatin (Gel), pectin (Pec), polyvinyl alcohol (PVA), dimethylacrylamide (DMAA), N-vinyl pyrrolidone (NVP), N-isopropylacrylamide (NIPAM), polyacrylic acid (PAA), and sodium carboxymethyl cellulose (CMC-Na).
[0014] Preferably, in S1, the aqueous solution includes one of acetic acid solution, hydrochloric acid solution, deionized water, phosphate buffer, Tris-HCl buffer, and sodium hydroxide solution;
[0015] Preferably, in S1, the oil phase includes one of mineral oil, paraffin oil, n-octanol, n-hexane, isooctane, polydimethylsiloxane, olive oil, soybean oil, HFE-7500, FC-40, and FC-70.
[0016] Preferably, in S2, the dispersed phase 1, dispersed phase 2 and continuous phase obtained in S1 are injected into the corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.1-1 mL / h, 0.2-2 mL / h and 1-15 mL / h, respectively, to form droplets.
[0017] Preferably, in S3, the crosslinking method is one of photocrosslinking, chemical crosslinking or ionic crosslinking.
[0018] Preferably, in the photocrosslinking, the light source is ultraviolet light with a wavelength of 320-470 nm and an illumination intensity of 5-50 mW / cm 2 , the illumination time is 5-600s; in the chemical crosslinking, the reaction temperature is 0-50°C, the reaction time is 1-120min, and the pH of the reaction system is 1-10; in the ionic crosslinking, the reaction time is 0.1-2h.
[0019] Preferably, the photocrosslinker is one of 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone, 2-hydroxy-2-methyl-1-phenylpropanone, lithium phenyl-2,4,6-trimethylbenzoylphosphinate, 1-hydroxycyclohexylphenyl ketone, α,α-dimethoxy-α-phenylacetophenone, and benzoin dimethyl ether.
[0020] Preferably, the chemical cross-linking agent is one of glutaraldehyde, carbodiimide cross-linking agent, and dithiothreitol, and the concentration of the cross-linking agent is 0.1-10 mg / mL.
[0021] Preferably, the ionic crosslinking agent is one of calcium ion salt solution, barium ion salt solution, strontium ion salt solution, zinc ion salt solution, iron ion salt solution, aluminum ion salt solution, magnesium ion salt solution, sodium tripolyphosphate, phosphate, and sodium citrate, and the crosslinking agent concentration is 0.01-10 mg / mL.
[0022] The present invention also provides a high-drug-loaded microgel prepared by the preparation method.
[0023] Compared with the prior art, the present invention has the following advantages and technical effects:
[0024] The present invention discloses a high-drug-loading microgel and a preparation method thereof. The high-drug-loading microgel is prepared by combining microfluidic technology with an antisolvent precipitation mechanism, achieving multiple significant technical effects: (1) the antisolvent precipitation principle is utilized to promote the precipitation of drugs inside the microgel and partially form drug crystals, effectively avoiding drug loss, greatly improving the drug loading capacity of the microgel for hydrophobic drugs, and solving the core problem of low encapsulation efficiency of traditional hydrophilic gel carriers; (2) diversified crosslinking methods such as chemical crosslinking, photocrosslinking, and ionic crosslinking can be adopted, which can be flexibly selected according to different application scenarios to fully meet the differentiated needs of biomedicine, tissue engineering and other fields; (3) the technical bottleneck of hydrophilic gel being difficult to encapsulate hydrophobic drugs is broken through, providing a new strategy for hydrophobic drug loading and controlled release, and significantly expanding the scope of application of hydrogel materials in the field of drug delivery; (4) the partial crystal structure formed by the uniform precipitation of drugs inside the microgel effectively regulates the drug release kinetics, significantly reduces the burst effect, and realizes long-term and stable release of drugs, providing reliable technical support for improving drug treatment effects and optimizing clinical applications.
[0025] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] Figure 1 Schematic diagram of the microfluidic device, where Figure 1a in the figure is the preparation of drug-loaded microgels by flow focusing method. Figure 1 b in the figure is the co-flow method for preparing drug-loaded microgels.
[0027] Figure 2 Light microscopy images of the drug-free PEGDA microgel provided in Comparative Example 1, the Mps@PEGDA microgel provided in Example 7, the Ibu@PEGDA microgel provided in Example 8, and the Fen@PEGDA microgel provided in Example 9. The scale is 200 μm.
[0028] Figure 3 Light microscopy images of the drug-free CS microgel provided in Comparative Example 2, the Mps@CS microgel provided in Example 10, the Ibu@CS microgel provided in Example 11, and the Fen@CS microgel provided in Example 6, with a scale of 200 μm.
[0029] Figure 4 The differential scanning calorimetry (DSC) curve of the Fen@PEGDA microgel provided in Example 9;
[0030] Figure 5 The differential scanning calorimetry (DSC) curve of the Fen@CS microgel provided in Example 6;
[0031] Figure 6 Statistical graphs of drug loading and encapsulation efficiency of the microgel (PEGDA (D)) of Example 6, Example 9, and Comparative Example 3;
[0032] Figure 7 Statistical graph of drug loading and encapsulation efficiency of Ibu by microgel (PEGDA (D)) provided in Example 8, Example 11 and Comparative Example 4. DETAILED DESCRIPTION
[0033] The technical solution of the present invention is further described below with reference to the accompanying drawings and embodiments.
[0034] Unless otherwise defined, technical or scientific terms used in the present invention shall have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs.
[0035] Source of test materials:
[0036] In the present invention, unless otherwise specified, other test materials and instruments and equipment are conventional test materials in this field and can be purchased through commercial channels.
[0037] Use Figure 1 The microfluidic device shown was used to prepare the high drug loading microgels described in Examples 1-6.
[0038] Example 1
[0039] A method for preparing a high-drug-loaded microgel comprises the following steps:
[0040] S1. Dissolve 50 mg of Fen in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of CS in 25 mL of 1% acetic acid solution as dispersed phase 2; and use paraffin oil as the continuous phase.
[0041] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0042] S3. Add glutaraldehyde at a concentration of 1 mg / mL to the droplets obtained in S2, and perform chemical crosslinking at 25° C. and a reaction system pH of 5 for 30 minutes to obtain a high-drug-loading microgel.
[0043] Example 2
[0044] A method for preparing a high-drug-loaded microgel comprises the following steps:
[0045] S1. Dissolve 50 mg of Ibu in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of CS in 25 mL of 1% acetic acid solution as dispersed phase 2; and use paraffin oil as the continuous phase.
[0046] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0047] S3. Add glutaraldehyde at a concentration of 1 mg / mL to the droplets obtained in S2, and perform chemical crosslinking at 25° C. and a reaction system pH of 5 for 30 minutes to obtain a high-drug-loading microgel.
[0048] Example 3
[0049] A method for preparing a high-drug-loaded microgel comprises the following steps:
[0050] S1. Dissolve 50 mg of Ibu in 10 mL of acetonitrile as dispersed phase 1; dissolve 50 mg of CS in 25 mL of 1% acetic acid solution as dispersed phase 2; and use paraffin oil as the continuous phase.
[0051] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0052] S3. Add glutaraldehyde at a concentration of 1 mg / mL to the droplets obtained in S2, and perform chemical crosslinking at 25° C. and a reaction system pH of 5 for 30 minutes to obtain a high-drug-loading microgel.
[0053] Example 4
[0054] S1. Dissolve 50 mg of Fen in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of CS in 25 mL of 1% acetic acid solution as dispersed phase 2; and use paraffin oil as the continuous phase.
[0055] S2, injecting the dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into the corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.5 mL / h, 1 mL / h, and 10 mL / h, respectively, to form droplets;
[0056] S3. Add glutaraldehyde at a concentration of 1 mg / mL to the droplets obtained in S2, and perform chemical crosslinking at 25° C. and a reaction system pH of 5 for 30 minutes to obtain a high-drug-loading microgel.
[0057] Example 5
[0058] S1. Dissolve 50 mg of Fen in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of PEGDA and 1 mg of photocrosslinker lithium phenyl-2,4,6-trimethylbenzoylphosphinate in 10 mL of deionized water as dispersed phase 2; and use paraffin oil as the continuous phase.
[0059] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0060] S3, at a wavelength of 365nm and an intensity of 10mW / cm 2 The droplets obtained by S2 were irradiated under ultraviolet light and photocrosslinked for 2 min to obtain high-drug-loading microgels.
[0061] Example 6
[0062] A high drug loading microgel, the preparation method comprises the following steps:
[0063] S1. Dissolve 50 mg of Fen in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of CS in 25 mL of 1% acetic acid solution as dispersed phase 2; and use mineral oil as the continuous phase.
[0064] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0065] S3. Glutaraldehyde was added to the droplets obtained in S2 at a concentration of 1 mg / mL, and chemical crosslinking was performed at 25° C. and a pH of 5 for 30 min to obtain Fen@CS microgels.
[0066] Example 7
[0067] A high drug loading microgel, the preparation method comprises the following steps:
[0068] S1. Dissolve 50 mg of methylprednisolone in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of PEGDA and 1 mg of the photocrosslinker lithium phenyl-2,4,6-trimethylbenzoylphosphinate in 10 mL of deionized water as dispersed phase 2; and use paraffin oil as the continuous phase.
[0069] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0070] S3, at a wavelength of 365nm and an intensity of 10mW / cm 2 The droplets obtained by S2 were irradiated under UV light and photocrosslinked for 2 min to obtain Mps@PEGDA microgels.
[0071] Example 8
[0072] A high drug loading microgel, the preparation method comprises the following steps:
[0073] S1. Dissolve 50 mg of Ibu in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of PEGDA and 1 mg of the photocrosslinker lithium phenyl-2,4,6-trimethylbenzoylphosphinate in 10 mL of deionized water as dispersed phase 2; and use paraffin oil as the continuous phase.
[0074] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0075] S3, at a wavelength of 365nm and an intensity of 10mW / cm 2 The droplets obtained by S2 were irradiated under UV light and photocrosslinked for 2 min to obtain Ibu@PEGDA microgels.
[0076] Example 9
[0077] A high drug loading microgel, the preparation method comprises the following steps:
[0078] S1. Dissolve 50 mg of Fen in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of PEGDA and 1 mg of photocrosslinker lithium phenyl-2,4,6-trimethylbenzoylphosphinate in 10 mL of deionized water as dispersed phase 2; and use paraffin oil as the continuous phase.
[0079] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0080] S3, at a wavelength of 365nm and an intensity of 10mW / cm 2 The droplets obtained by S2 were irradiated under UV light and photocrosslinked for 2 min to obtain Fen@PEGDA microgels.
[0081] Example 10
[0082] A high drug loading microgel, the preparation method comprises the following steps:
[0083] S1. Dissolve 50 mg of methylprednisolone in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of CS in 25 mL of 1% acetic acid solution as dispersed phase 2; and use mineral oil as the continuous phase.
[0084] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0085] S3. Add glutaraldehyde at a concentration of 1 mg / mL to the droplets obtained in S2, and perform chemical crosslinking at 25° C. and a reaction system pH of 5 for 30 min to obtain Mps@CS microgels.
[0086] Example 11
[0087] A method for preparing a high-drug-loaded microgel comprises the following steps:
[0088] S1. Dissolve 50 mg of Ibu in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of CS in 25 mL of 1% acetic acid solution as dispersed phase 2; and use mineral oil as the continuous phase.
[0089] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0090] S3. Add glutaraldehyde at a concentration of 1 mg / mL to the droplets obtained in S2, and perform chemical crosslinking at 25°C and a reaction system pH of 5 for 30 min to obtain Ibu@CS microgels.
[0091] Comparative Example 1
[0092] Provided is a PEGDA microgel without drug encapsulation, and a preparation method comprising the following steps:
[0093] S1. Disperse phase 1 is prepared by dissolving 10 mL of dimethyl sulfoxide; dissolving 50 mg of PEGDA and 1 mg of lithium phenyl-2,4,6-trimethylbenzoylphosphinate, a photocrosslinker, in 10 mL of deionized water as disperse phase 2; and using paraffin oil as the continuous phase.
[0094] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0095] S3, at a wavelength of 365nm and an intensity of 10mW / cm 2 The droplets obtained by S2 were irradiated under ultraviolet light and photocrosslinked for 2 min to obtain PEGDA microgels without drug entrapment.
[0096] Comparative Example 2
[0097] A method for preparing a high-drug-loaded microgel comprises the following steps:
[0098] S1, 10 mL of dimethyl sulfoxide as dispersed phase 1; 50 mg of CS dissolved in 25 mL of 1% acetic acid solution as dispersed phase 2; paraffin oil as continuous phase;
[0099] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0100] S3. Add glutaraldehyde at a concentration of 1 mg / mL to the droplets obtained in S2, and perform chemical crosslinking at 25° C. and a reaction system pH of 5 for 30 min to obtain CS microgels without drug entrapment.
[0101] Comparative Example 3
[0102] S1. Dissolve 50 mg of Fen in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of PEGDA and 1 mg of photocrosslinker lithium phenyl-2,4,6-trimethylbenzoylphosphinate in 10 mL of dimethyl sulfoxide as dispersed phase 2; and use paraffin oil as the continuous phase.
[0103] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0104] S3, at a wavelength of 365nm and an intensity of 10mW / cm 2 The droplets obtained by S2 were irradiated under ultraviolet light and photocrosslinked for 2 min to obtain drug-loaded microgels.
[0105] Comparative Example 4
[0106] S1. Dissolve 50 mg of Ibu in 10 mL of dimethyl sulfoxide as dispersed phase 1; dissolve 50 mg of PEGDA and 1 mg of the photocrosslinker lithium phenyl-2,4,6-trimethylbenzoylphosphinate in 10 mL of dimethyl sulfoxide as dispersed phase 2; and use paraffin oil as the continuous phase.
[0107] S2, injecting dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.2 mL / h, 0.4 mL / h, and 5 mL / h, respectively, to form droplets;
[0108] S3, at a wavelength of 365nm and an intensity of 10mW / cm 2 The droplets obtained by S2 were irradiated under ultraviolet light and photocrosslinked for 2 min to obtain drug-loaded microgels.
[0109] The effects of the high-drug-loaded microgels provided in Examples 6-11 and Comparative Examples 1-4 were verified through the following experiments.
[0110] The PEGDA microgel without drug loading provided in Comparative Example 1, the Mps@PEGDA microgel provided in Example 7, the Ibu@PEGDA microgel provided in Example 8, and the Fen@PEGDA microgel provided in Example 9 were analyzed by optical microscopy. Figure 2 .
[0111] Depend on Figure 2 It can be seen that the precipitated drug is evenly distributed in the microgel.
[0112] The CS microgel without drug loading provided in Comparative Example 2, the Mps@CS microgel provided in Example 10, the Ibu@CS microgel provided in Example 11, and the Fen@CS microgel provided in Example 6 were analyzed by optical microscopy. Figure 3 .
[0113] Depend on Figure 3 It can be seen that the precipitated drug is evenly distributed in the microgel.
[0114] The differential scanning calorimetry (DSC) analysis of the Fen@PEGDA microgel provided in Example 9 showed that Figure 4 .
[0115] Depend on Figure 4 It can be seen that the Fen@PEGDA microgel provided in Example 9 exhibits an obvious endothermic peak at around 82°C, indicating that the drug precipitated in the PEGDA microgel has partially formed a crystalline structure.
[0116] The Fen@CS microgel provided in Example 6 was subjected to differential scanning calorimetry (DSC) analysis, and the results were as follows: Figure 5 .
[0117] Depend on Figure 5 It can be seen that the Fen@CS microgel provided in Example 6 exhibits an obvious endothermic peak at around 82°C, indicating that the drug precipitated in the CS microgel has partially formed a crystalline structure.
[0118] The drug loading and encapsulation efficiency of the microgels of Example 6, Example 9 and Comparative Example 3 were analyzed. Figure 6 .
[0119] The calculation formula of drug loading is as follows:
[0120] Drug loading capacity = mass of drug in microgel after drying / total mass of drug-loaded microgel after drying * 100%
[0121] The encapsulation efficiency is calculated as follows:
[0122] Encapsulation efficiency = mass of drug in microgel after drying / total mass of drug added * 100%
[0123] Depend on Figure 6 It can be seen that by using antisolvent precipitation, the drug loading capacity of microgel for Fen increased by 5.4 times and the encapsulation efficiency increased by 2.9 times.
[0124] The drug loading and encapsulation efficiency of the microgels provided in Example 8, Example 11 and Comparative Example 4 were analyzed, and the calculation formula was the same as above. The results are as follows: Figure 7 .
[0125] Depend on Figure 7It can be seen that by using antisolvent precipitation, the drug loading capacity of microgel for Ibu increased by 5.2 times and the encapsulation efficiency increased by 2.8 times.
[0126] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the same. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solutions of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.
Claims
1. A method for preparing a high-drug-loaded microgel, characterized in that: The following steps are involved: S1. Dissolve the hydrophobic drug in an organic solvent as dispersed phase 1; dissolve the polymer material in an aqueous solution as dispersed phase 2; and use the oil phase as the continuous phase; S2, injecting the dispersed phase 1, dispersed phase 2 and continuous phase obtained in S1 into corresponding channels of the microfluidic device through a syringe pump to form droplets; S3. Cross-link the droplets obtained in S2 to obtain a high drug loading microgel.
2. The preparation method according to claim 1, characterized in that In S1, the mass concentration of the hydrophobic drug in the dispersed phase 1 is 1%-10%, and the hydrophobic drug includes one of ibuprofen, fenofibrate, methylprednisolone, naproxen, celecoxib, dexamethasone, paclitaxel, atorvastatin, itraconazole, and ritonavir.
3. The preparation method according to any one of claims 1 or 2, characterized in that In S1, the organic solvent includes one of dimethyl sulfoxide, acetonitrile, methanol, ethanol, acetone, propylene glycol, isopropanol, ethylene glycol, tetrahydrofuran, N-methylpyrrolidone, and dimethylformamide.
4. The preparation method according to claim 1, characterized in that In S1, the mass concentration of the polymer material in the dispersed phase 2 is 1%-10%, and the polymer material includes one of chitosan, polyethylene glycol diacrylate, sodium alginate, gelatin, pectin, polyvinyl alcohol, dimethylacrylamide, N-vinyl pyrrolidone, N-isopropylacrylamide, polyacrylic acid, and sodium carboxymethyl cellulose.
5. The preparation method according to any one of claims 1 or 4, characterized in that In S1, the aqueous solution includes one of acetic acid solution, hydrochloric acid solution, deionized water, phosphate buffer, Tris-HCl buffer, and sodium hydroxide solution.
6. The preparation method according to claim 1, characterized in that: In S1, the oil phase includes one of mineral oil, paraffin oil, n-octanol, n-hexane, isooctane, polydimethylsiloxane, olive oil, soybean oil, HFE-7500, FC-40, and FC-70.
7. The preparation method according to claim 1, characterized in that: In S2, dispersed phase 1, dispersed phase 2, and continuous phase obtained in S1 were injected into corresponding channels of the microfluidic device through a syringe pump at flow rates of 0.1-1 mL / h, 0.2-2 mL / h, and 1-15 mL / h, respectively, to form droplets.
8. The preparation method according to claim 1, characterized in that: In S3, the crosslinking method is one of photocrosslinking, chemical crosslinking or ionic crosslinking.
9. The preparation method according to claim 8, characterized in that: In the photocrosslinking, the light source is ultraviolet light with a wavelength of 320-470 nm and an illumination intensity of 5-50 mW / cm 2 , the illumination time is 5-600s; in the chemical crosslinking, the reaction temperature is 0-50°C, the reaction time is 1-120min, and the pH of the reaction system is 1-10; in the ionic crosslinking, the reaction time is 0.1-2h.
10. The high drug loading microgel prepared by the preparation method according to any one of claims 1 to 9.