CN108102082B - Polycaprolactone-based diethyl sulfopropyl betaine, preparation method thereof and construction method of polycaprolactone-based diethyl sulfopropyl betaine as drug release carrier - Google Patents
Polycaprolactone-based diethyl sulfopropyl betaine, preparation method thereof and construction method of polycaprolactone-based diethyl sulfopropyl betaine as drug release carrier Download PDFInfo
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- -1 diethyl sulfopropyl betaine Chemical compound 0.000 title claims abstract description 55
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 229960003237 betaine Drugs 0.000 title claims abstract description 51
- 229920001610 polycaprolactone Polymers 0.000 title claims abstract description 38
- 239000004632 polycaprolactone Substances 0.000 title claims abstract description 38
- 229940079593 drug Drugs 0.000 title claims abstract description 30
- 239000003814 drug Substances 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000010276 construction Methods 0.000 title abstract description 8
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 9
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 74
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 63
- 239000000243 solution Substances 0.000 claims description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
- 239000011259 mixed solution Substances 0.000 claims description 23
- 238000013270 controlled release Methods 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
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- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 19
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- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 claims description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 8
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- 229910021641 deionized water Inorganic materials 0.000 claims description 7
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 238000004108 freeze drying Methods 0.000 claims description 5
- 238000003760 magnetic stirring Methods 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- 238000002390 rotary evaporation Methods 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 5
- 238000009210 therapy by ultrasound Methods 0.000 claims description 5
- 238000005119 centrifugation Methods 0.000 claims description 2
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- 238000013267 controlled drug release Methods 0.000 claims 2
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- 238000001727 in vivo Methods 0.000 description 12
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- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/68—Polyesters containing atoms other than carbon, hydrogen and oxygen
- C08G63/688—Polyesters containing atoms other than carbon, hydrogen and oxygen containing sulfur
- C08G63/6882—Polyesters containing atoms other than carbon, hydrogen and oxygen containing sulfur derived from hydroxy carboxylic acids
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Abstract
The invention discloses polycaprolactone-based diethyl sulfopropyl betaine, a preparation method thereof and a construction method of the polycaprolactone-based diethyl sulfopropyl betaine as a drug release carrier, wherein the carrier is formed by self-assembling polycaprolactone-based diethyl sulfopropyl betaine (PC L-SB), a hydrophobic PC L segment is a carrier inner core, and hydrophilic hydroxyethyl diethyl sulfopropyl betaine is a shell layer.
Description
Technical Field
The invention belongs to the field of biomedical polymer materials, and relates to polycaprolactone-based diethyl sulfopropyl betaine, a preparation method thereof and a construction method of the polycaprolactone-based diethyl sulfopropyl betaine as a drug release carrier.
Background
The polymer micelle formed by self-assembling the amphiphilic block polymer in the aqueous solution is used as a hydrophobic anticancer drug delivery carrier, and has the advantages of increasing the solubility of the drug, being not easy to be captured by a reticuloendothelial system, reducing toxic and side effects and the like, so that the drug can be delivered to a required pathological tissue in a targeted manner, high-efficiency intracellular delivery, drug controlled release and effective treatment are realized, a huge application prospect is shown in the field of disease treatment, particularly tumor treatment, and the hydrophobic anticancer drug delivery carrier is widely researched by scientific research workers. The existing drug controlled release carrier based on amphiphilic block polymerization mainly focuses on a special microenvironment of a focus part, constructs an intelligent response type nano carrier, can trigger the targeted drug release of the carrier through the change of the microenvironment, and improves the treatment effect. In various in vitro studies, the carrier shows good experimental effect. With the progress of research, in vivo research shows that when the nano-carrier is administered through vein, the nano-carrier is usually cleared by the immune system of human body within a short time, and the long-acting and targeted administration can hardly be achieved. The reason for this is mainly that when the carrier material is in contact with blood/body fluid, a large amount of protein will adhere to the surface of the carrier material, reducing the drug utilization efficiency, and more importantly, the protein may be recognized and eliminated by the immune system of human body, so that the therapeutic effect is limited to a certain extent. Therefore, the basic problem to be solved by the nano preparation is that the nano preparation gives the carrier material the non-specific adsorption performance of protein, improves the stability of the amphiphilic carrier in a microenvironment in vivo, avoids phagocytosis of macrophages, and achieves the effect of long circulation in vivo.
Polyethylene glycol is a commonly used material for improving the protein adhesion resistance of a carrier, but terminal hydroxyl groups of the polyethylene glycol are easily oxidized in vivo to form aldehyde groups, so that the terminal hydroxyl groups are combined with amino groups of proteins in vivo to influence the biological activity of the proteins and even inactivate the proteins, and the application effect of the polyethylene glycol is influenced to a certain extent. The zwitterionic polymer can form a hydration layer on the surface of the zwitterionic polymer through excellent hydrophilic property, prevent protein adhesion and have good protein adhesion resistance. And has good biocompatibility. The hydrophilic property of the carrier can be used as a hydrophilic section of amphiphilic block polymerization to be copolymerized with a hydrophobic polymer, so that a nano-drug controlled release carrier material with protein resistance can be formed, the in-vivo long-circulating property of the carrier material is improved, and the treatment effect on diseases is improved.
In order to overcome the defect of poor long circulation capability of an amphiphilic carrier material, a drug controlled release carrier material with protein nonspecific adhesion resistance is constructed by modifying a hydrophobic caprolactone polymer with zwitterion hydroxyethyl diethylsulfopropyl betaine (SB), and the problem of poor in vivo long circulation capability of the conventional carrier material can be effectively solved.
Disclosure of Invention
The invention aims to overcome the defect of poor in-vivo long circulation capability of the existing drug controlled release carrier and provide the drug controlled release carrier based on polycaprolactone-based diethylsulfopropylbetaine (PC L-SB) with good biocompatibility and protein nonspecific adhesion resistance.
The invention aims to overcome the defects of the prior art and provides the PC L-SB polymer, a preparation method thereof and a construction method of a PC L-SB-based drug controlled release carrier.
The above object of the present invention is achieved by the following means.
A polycaprolactone-based diethyl sulfopropyl betaine polymer is characterized in that the polymer is prepared by modifying hydrophobic caprolactone polymer with zwitter-ion hydroxyethyl diethyl sulfopropyl betaine; the structural formula is shown as follows, wherein n is a natural number of 10-540;
the preparation method of the polycaprolactone-based diethyl sulfopropyl betaine polymer is characterized by comprising the following steps of:
(1) dissolving diethyl ethanolamine in toluene, and preparing a diethyl ethanolamine solution with the mass concentration of 2.6-35% by magnetic stirring; simultaneously dissolving propane sultone in toluene, and magnetically stirring to form a propane sultone solution with the mass concentration of 2.6-35%;
(2) dropwise adding the propane sultone solution obtained in the step (1) into an isovolumetric diethylethanolamine solution at 50-70 ℃ under the condition of introducing nitrogen, continuing to react for 12-36 h, stopping the reaction, filtering the product, and recrystallizing in isopropanol to obtain hydroxyethyl diethylsulfopropyl betaine;
(3) dissolving caprolactone and hydroxyethyl diethyl sulfopropyl betaine obtained in the step (2) in a toluene solution, wherein the mass concentration of the caprolactone is 3-75%, the concentration of the hydroxyethyl diethyl sulfopropyl betaine is 0.2-2.5%, uniformly mixing, adding stannous octoate to enable the mass concentration to be 0.1%, and carrying out reflux reaction at 100-140 ℃ for 12-48 h under the protection of nitrogen to obtain a mixed solution;
(4) and (3) cooling the mixed solution obtained in the step (3) to room temperature, removing the toluene solution by rotary evaporation, dissolving the obtained solid substance with dichloromethane, wherein the ratio of dichloromethane to the solid substance is 0.4-0.8 (ml/g), adding the obtained solid substance into diethyl ether at 4 ℃, wherein the ratio of diethyl ether to the solid substance is 3-15 (ml/g), and finally performing vacuum drying for 24-72 h to obtain the polycaprolactone-based diethyl sulfopropyl betaine.
The dropping speed of the step 2) is 3-8 ml/min.
The drug controlled release carrier of the polycaprolactone-based diethyl sulfopropyl betaine polymer is characterized in that the carrier is formed by self-assembling polycaprolactone-based diethyl sulfopropyl betaine, a hydrophobic polycaprolactone (PC L) segment is used as a carrier inner core, hydrophilic hydroxyethyl diethyl Sulfopropyl Betaine (SB) is used as a shell layer, polycaprolactone-based diethyl sulfopropyl betaine is dissolved in dimethyl sulfoxide (DMSO) and the concentration of the polycaprolactone-based diethyl sulfopropyl betaine is 0.1-10 mg/ml, the solution is dropwise added into 10 times of volume of deionized water under the stirring condition, and then stirring is carried out at room temperature for 2-8 hours to form the polycaprolactone-based diethyl sulfopropyl betaine carrier.
The preparation method of the drug controlled release system carrier constructed by the release carrier comprises the following steps:
(1) dissolving adriamycin (DOX) and PC L-SB in DMSO, wherein the concentration of the DOX is 0.1-4 mg/ml, and the mass concentration of the PC L-SB is 0.1-10 mg/ml;
(2) dripping the DOX/PC L-SB mixed solution obtained in the step (1) into 10 times volume of deionized water under the stirring condition, carrying out ultrasonic treatment for 10-30 min, and then stirring at room temperature for 2-8 h to obtain a mixed solution;
(3) and (3) centrifuging the mixed solution obtained in the step (2) to remove residual DOX, and freeze-drying the supernatant to obtain the DOX-loaded controlled release system carrier (DOX @ PC L-SB).
The centrifugation condition is 15000rpm, and 15-30 min.
The particle size of the drug controlled release carrier prepared by the invention is 20-450 nm.
The drug controlled release carrier has the characteristic of resisting non-specific protein adhesion.
Compared with the prior art, the PC L-SB polymer prepared by the method has the advantages that the operation is simple, the particle size of the constructed PC L-SB nano micelle can be controlled to be 20-450 nm, the carrier material has good biocompatibility and no cytotoxicity, a plurality of hydrophobic drugs (such as DOX) can be loaded, the loading amount and the controlled release rate of the drugs can be controlled by the molecular weight of the PC L section, more importantly, the PC L-SB carrier has good protein adsorption resistance, the structure and performance stability can be maintained in a complex protein medium, the circulation time of the drugs in a body can be obviously prolonged, and the preparation method can be prolonged by 5-16 times compared with the traditional amphiphilic micelle.
Drawings
FIG. 1: is a chart of the formation process of hydroxyethyl diethyl sulfopropyl betaine;
FIG. 2 is a diagram showing the formation process of polycaprolactone-based diethylsulfopropyl betaine (PC L-SB);
FIG. 3 is a transmission electron micrograph of DOX @ PC L-SB nanoparticles.
Detailed Description
The technical scheme of the invention is further explained by combining specific examples.
The reagents used in the following examples include essentially the following: diethylethanolamine, propane sultone, stannous octoate, toluene, dichloromethane, Doxorubicin (DOX), sodium chloride, dimethyl sulfoxide (DMSO), and diethyl ether.
Example 1: preparation of polycaprolactone based diethyl sulfopropyl betaine (I)
(1) Weighing 1.17g of diethylethanolamine, dissolving the diethylethanolamine in 50ml of toluene, and preparing a diethylethanolamine solution with the mass concentration of 2.6% by magnetic stirring;
(2) weighing 1.2g of propane sultone, adding the propane sultone into 50ml of toluene, and magnetically stirring to form a propane sultone solution with the mass concentration of 2.7%;
(3) and (3) dropwise adding the propane sultone solution obtained in the step (2) into the diethylethanolamine solution obtained in the step (1) at 50 ℃ under the condition of introducing nitrogen, wherein the dropwise adding speed is 3 ml/min. After the reaction is continued for 12 hours, stopping the reaction, filtering the product and recrystallizing the product in isopropanol to obtain hydroxyethyl diethyl Sulfopropyl Betaine (SB), wherein the reaction process is shown in figure 1;
(4) dissolving 1.34g of caprolactone and 0.22g of SB in 50ml of toluene solution, wherein the mass concentration of the caprolactone is 3 percent, and the concentration of the SB is 0.5 percent; after being mixed evenly, 0.04g of stannous octoate is added, and the reflux reaction is carried out for 12 hours at 120 ℃ under the protection of nitrogen, wherein the reaction process is shown in figure 2;
(5) and (3) cooling the mixed solution obtained in the step (4) to room temperature, removing the toluene solution by rotary evaporation, dissolving the obtained solid substance with 1ml of dichloromethane, adding the dissolved solid substance into 20ml of diethyl ether at the temperature of 4 ℃, and finally drying in vacuum for 24 hours to obtain polycaprolactone-based diethylsulfopropyl betaine (PC L-SB), wherein n is 10.
Example 2: preparation of polycaprolactone based diethyl sulfopropyl betaine (II)
(1) Weighing 11.7g of diethylethanolamine, dissolving the diethylethanolamine in 50ml of toluene, and preparing a diethylethanolamine solution with the mass concentration of 21.27% by magnetic stirring;
(2) weighing 12.2g of propane sultone, adding the propane sultone into 50ml of toluene, and magnetically stirring to form a propane sultone solution with the mass concentration of 22%;
(3) and (3) dropwise adding the propane sultone solution obtained in the step (2) into the diethylethanolamine solution obtained in the step (1) at the temperature of 60 ℃ under the condition of introducing nitrogen, wherein the dropwise adding speed is 6 ml/min. After the reaction is continued for 24 hours, stopping the reaction, filtering the product and recrystallizing the product in isopropanol to obtain hydroxyethyl diethyl Sulfopropyl Betaine (SB);
(4) dissolving 50.81g of caprolactone and 2.27g of SB in 50ml of toluene solution, wherein the mass concentration of the caprolactone is 53 percent, and the concentration of the SB is 2.5 percent; after being mixed evenly, 0.04g of stannous octoate is added, and reflux reaction is carried out for 24 hours at 100 ℃ under the protection of nitrogen;
(5) and (3) cooling the mixed solution obtained in the step (4) to room temperature, removing the toluene solution by rotary evaporation, dissolving the obtained solid substance by using 30ml of dichloromethane, adding the dissolved solid substance into 400ml of diethyl ether at the temperature of 4 ℃, and finally drying the dissolved solid substance in vacuum for 48 hours to obtain polycaprolactone-based diethylsulfopropyl betaine (PC L-SB), wherein n is 47.
Example 3: preparation of polycaprolactone based diethyl sulfopropyl betaine (III)
(1) Weighing 23.4g of diethylethanolamine, dissolving the diethylethanolamine in 50ml of toluene, and preparing a diethylethanolamine solution with the mass concentration of 35% by magnetic stirring;
(2) weighing 24.4g of propane sultone, adding the propane sultone into 50ml of toluene, and magnetically stirring to form a propane sultone solution with the mass concentration of 35%;
(3) and (3) dropwise adding the propane sultone solution obtained in the step (2) into the diethylethanolamine solution obtained in the step (1) at the temperature of 60 ℃ under the condition of introducing nitrogen, wherein the dropwise adding speed is 8 ml/min. After the reaction is continued for 36 hours, stopping the reaction, filtering the product and recrystallizing the product in isopropanol to obtain hydroxyethyl diethyl Sulfopropyl Betaine (SB);
(4) dissolving 130.5g of caprolactone and 0.48g of SB in 50ml of toluene solution, wherein the mass concentration of the caprolactone is 75 percent, and the concentration of the SB is 0.2 percent; after being mixed evenly, 0.04g of stannous octoate is added, and reflux reaction is carried out for 48 hours at 140 ℃ under the protection of nitrogen;
(5) and (3) cooling the mixed solution obtained in the step (4) to room temperature, removing the toluene solution by rotary evaporation, dissolving the obtained solid substance by using 100ml of dichloromethane, adding the dissolved solid substance into 500ml of diethyl ether at the temperature of 4 ℃, and finally drying in vacuum for 72 hours to obtain polycaprolactone-based diethylsulfopropyl betaine (PC L-SB), wherein n is 540.
Example 4 construction of PC L-SB based drug controlled Release System (I)
(1) 0.1mg of adriamycin (DOX) and 0.1mg of PC L-SB are weighed and dissolved in 1ml of DMSO, and the concentration of the adriamycin (DOX) and the PC L-SB is 0.1 mg/ml;
(2) dropwise adding the DOX/PC L-SB mixed solution obtained in the step (1) into 10ml of deionized water under the stirring condition, performing ultrasonic treatment for 10min, and stirring at room temperature for 2h to obtain a mixed solution;
(3) centrifuging the mixed solution obtained in the step (2) (15000rpm,15min) to remove residual DOX, and freeze-drying the supernatant to obtain a DOX-loaded controlled release system carrier (DOX @ PC L-SB), wherein the particle size of the obtained nanoparticles is 20nm as shown in figure 3, and the in vivo pharmacokinetic experiment of rats proves that the half-life period of the DOX @ PC L-SB in vivo drugs is 280 min.
Example 5 construction of PC L-SB-based drug controlled Release System (II)
(1) Weighing 2mg of adriamycin (DOX) and 5mg of PC L-SB, dissolving in 1ml of DMSO, wherein the concentration of the DOX is 2mg/ml, and the concentration of the PC L-SB is 5 mg/ml;
(2) dropwise adding the DOX/PC L-SB mixed solution obtained in the step (1) into deionized water with the volume being 10 times that of the mixed solution under the stirring condition, carrying out ultrasonic treatment for 20min, and then stirring for 4h at room temperature to obtain a mixed solution;
(3) centrifuging the mixed solution obtained in the step (2) (15000rpm,20min) to remove residual DOX, and freeze-drying the supernatant to obtain a DOX-loaded controlled release system carrier (DOX @ PC L-SB), wherein the particle size of the obtained nanoparticles is 20nm, and the in vivo pharmacokinetic experiment of rats proves that the drug half-life of DOX @ PC L-SB is 120 min.
Example 6 construction of PC L-SB-based drug controlled Release System (III)
(1) Weighing 4mg of adriamycin (DOX) and 10mg of PC L-SB, dissolving in 1ml of DMSO, wherein the concentration of the DOX is 4mg/ml, and the concentration of the PC L-SB is 10 mg/ml;
(2) dropwise adding the DOX/PC L-SB mixed solution obtained in the step (1) into 10 times of deionized water under the stirring condition, carrying out ultrasonic treatment for 30min, and then stirring at room temperature for 4h to obtain a mixed solution.
(3) Centrifuging the mixed solution obtained in the step (2) (15000rpm,30min) to remove residual DOX, and freeze-drying the supernatant to obtain a DOX-loaded controlled release system carrier (DOX @ PC L-SB), wherein the particle size of the obtained nanoparticles is 450nm, and the in vivo pharmacokinetic experiment of rats proves that the drug half-life of DOX @ PC L-SB is 160 min.
Although the method and the preparation technique of the present invention have been described by way of preferred embodiments, it will be apparent to those skilled in the art that the method and the technical route described herein can be modified or recombined to achieve the final preparation technique without departing from the content, spirit and scope of the present invention. It is expressly intended that all such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and content of the invention.
Claims (4)
1. A polycaprolactone-based diethyl sulfopropyl betaine polymer is characterized in that the polymer is prepared by modifying hydrophobic caprolactone polymer with zwitter-ion hydroxyethyl diethyl sulfopropyl betaine; the structural formula is shown as follows, wherein n is a natural number of 10-540;
the preparation method of the polycaprolactone-based diethyl sulfopropyl betaine polymer comprises the following steps:
(1) dissolving diethyl ethanolamine in toluene, and preparing a diethyl ethanolamine solution with the mass concentration of 2.6-35% by magnetic stirring; simultaneously dissolving propane sultone in toluene, and magnetically stirring to form a propane sultone solution with the mass concentration of 2.6-35%;
(2) dropwise adding the propane sultone solution obtained in the step (1) into an isovolumetric diethylethanolamine solution at 50-70 ℃ under the condition of introducing nitrogen, continuing to react for 12-36 h, stopping the reaction, filtering the product, and recrystallizing in isopropanol to obtain hydroxyethyl diethylsulfopropyl betaine;
(3) dissolving caprolactone and hydroxyethyl diethyl sulfopropyl betaine obtained in the step (2) in a toluene solution, wherein the mass concentration of the caprolactone is 3-75%, the concentration of the hydroxyethyl diethyl sulfopropyl betaine is 0.2-2.5%, uniformly mixing, adding stannous octoate to enable the mass concentration of the stannous octoate to be 0.1%, and carrying out reflux reaction at 100-140 ℃ for 12-48 hours under the protection of nitrogen to obtain a mixed solution;
(4) cooling the mixed solution obtained in the step (3) to room temperature, performing rotary evaporation to remove a toluene solution, dissolving the obtained solid substance with dichloromethane, wherein the ratio of dichloromethane to the solid substance is 0.4-0.8 ml/g, adding diethyl ether at 4 ℃, wherein the ratio of diethyl ether to the solid substance is 3-15 ml/g, and finally performing vacuum drying for 24-72 h to obtain polycaprolactone-based diethyl sulfopropyl betaine;
the dropping speed of the step (2) is 3-8 ml/min.
2. A drug controlled release carrier based on the polycaprolactone-based diethyl sulfopropyl betaine polymer of claim 1, which is characterized in that the carrier is formed by self-assembling polycaprolactone-based diethyl sulfopropyl betaine, a hydrophobic polycaprolactone segment is used as a carrier inner core, hydrophilic hydroxyethyl diethyl sulfopropyl betaine is used as a shell layer, polycaprolactone-based diethyl sulfopropyl betaine is dissolved in dimethyl sulfoxide, the concentration of the polycaprolactone-based diethyl sulfopropyl betaine is 0.1-10 mg/ml, a solution is formed, the solution is dropwise added into 10 times volume of deionized water under the stirring condition, and then stirring is carried out at room temperature for 2-8 hours, so that the polycaprolactone-based diethyl sulfopropyl betaine carrier is formed.
3. The controlled drug release carrier according to claim 2, which has anti-protein non-specific adhesion properties.
4. A method of preparing a carrier for a controlled drug release system according to claim 2, comprising the steps of:
(1) dissolving adriamycin and polycaprolactone-based diethyl sulfopropyl betaine polymer in dimethyl sulfoxide, wherein the concentration of the adriamycin is 0.1-4 mg/ml, and the mass concentration of the polycaprolactone-based diethyl sulfopropyl betaine polymer is 0.1-10 mg/ml;
(2) dropwise adding the adriamycin/polycaprolactone-based diethyl sulfopropyl betaine polymer mixed solution obtained in the step (1) into 10-time volume of deionized water under the stirring condition, carrying out ultrasonic treatment for 10-30 min, and then stirring at room temperature for 2-8 h to obtain a mixed solution;
(3) centrifuging the mixed solution obtained in the step (2) to remove residual adriamycin, and freeze-drying the supernatant to obtain the adriamycin-loaded controlled release system carrier;
the centrifugation condition of the step (3) is 15000rpm for 15-30 min;
the particle size of the drug controlled release carrier is 20-450 nm.
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