CN112121011A - Adriamycin corn starch grafted polymer micelle and preparation method thereof - Google Patents
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Abstract
The invention provides an adriamycin starch grafted polymer micelle and a preparation method thereof, wherein corn starch grafted polymer obtained by grafting zwitterionic Sulfobetaine (SB) and deoxycholic acid (DCA) on Corn Starch (CST) is used as a carrier to entrap a hydrophobic anti-tumor drug adriamycin, the particle size of the obtained adriamycin starch grafted polymer micelle (SB-CST-DCA) is less than 200nm, the drug loading rate is 5-16%, and the entrapment rate is 59-80%.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to an adriamycin corn starch grafted polymer micelle and a preparation method thereof.
Background
Doxorubicin (DOX) is a medicine with strong cell individuality, and has extremely strong antitumor activity due to the fact that the doxorubicine contains fat-soluble anthracycline aglycone, water-soluble brown sugar amine, acidic phenolic hydroxyl and basic amino. At present, the traditional Chinese medicine composition is widely applied to treatment of various cancers such as liver cancer, osteosarcoma and the like. However, adriamycin is mainly administered by injection, which easily causes phlebitis, liver function damage and body inflammation, and can directly cause death of patients in severe cases, and the development of adriamycin is limited by severe toxic and side effects in clinical application. Therefore, in the tumor treatment, the key point is to improve the treatment efficiency of the adriamycin and reduce the toxic and side effects. At present, the problem can be solved by embedding antitumor drugs in drug carriers in the biomedical field, such as doxorubicin liposomes, vesicles, dendrimers and the like, but the therapeutic effect is improved compared with that of simple doxorubicin, the problems of drug burst release, drug leakage and the like still exist, and not every carrier is suitable to be used as a drug carrier. An ideal drug carrier has good biocompatibility, biodegradability, good water solubility and stability, can encapsulate various antitumor drugs, does not have any interaction among the drugs, and the like, and has certain advantages for the polymer micelle.
The self-assembly micelle drug delivery system is a drug delivery system which is actively researched in the field of biological medicine in recent years, and the amphiphilic polymer is self-assembled into a core-shell structure in aqueous solution. It has the following advantages as a drug carrier: 1) the hydrophilic shell is used as a protective layer to protect the micelle core from being damaged, so that the micelle can realize long circulation in vivo; 2) the hydrophobic inner shell is used as a container for various hydrophobic drug molecules, can embed insoluble and protein polypeptide drugs and has higher drug-loading rate; 3) the structure of the micelle enables the micelle to have a selective permeation effect and has targeting effect on inflammatory tissues and tumor parts.
The amphiphilic material is the key for forming the self-assembled micelle, and the Starch (ST) is a natural drug carrier material, has good biocompatibility and biodegradability and has wide application value in the field of biomedicine. Due to the abundant hydroxyl functional groups in the molecular structure of the starch, the diversity of micelle response forms can be realized through hydrophobic modification, and the bioavailability and the in-vivo drug release performance of the drug-loaded micelle are improved.
The invention grafts the zwitterionic sulfobetaine and deoxycholic acid on the framework of Corn Starch (CST) to obtain an amphiphilic starch graft (SB-CST-DCA). Researches show that the polymer micelle can be self-assembled in an aqueous medium, and the insoluble antitumor drug adriamycin can be embedded in the inner core of the micelle to enhance the bioavailability. Through retrieval, a patent application or a literature report that the adriamycin drug-carrying micelle prepared by taking sulfobetaine and deoxycholic acid grafted corn starch as a drug carrier to promote the delivery efficiency of an antitumor drug is not available at present.
Disclosure of Invention
The invention aims to provide an adriamycin starch grafted polymer micelle and a preparation method thereof, wherein a polymer obtained by grafting zwitterionic Sulfobetaine (SB) and deoxycholic acid (DCA) on Corn Starch (CST) is used as a carrier to entrap a hydrophobic anti-tumor drug adriamycin, and the particle size of the obtained adriamycin starch grafted polymer micelle (SB-CST-DCA) is less than 200nm, the drug loading rate is 5-16%, and the entrapment rate is 59-80%.
In order to achieve the purpose, the invention adopts the following technical scheme:
an adriamycin corn starch grafted polymer micelle is prepared by the following method:
s1, synthesis of a zwitterionic starch graft polymer: preparing the corn starch into an alkalized starch suspension by using a sodium hydroxide solution, and stirring and reacting for 0.5-1.5 h at the temperature of 40-70 ℃; dissolving sulfobetaine in water, adding the solution into the alkalized starch suspension, and stirring and reacting for 0.5-8.0 h at 40-70 ℃; neutralizing the reaction system to be neutral by using glacial acetic acid, precipitating by using methanol, centrifuging to obtain a precipitate, and freeze-drying to obtain the amphoteric ion starch graft polymer;
s2, synthesis of a corn starch graft polymer: dissolving 1-ethyl- (3-dimethylaminopropyl) -carbodiimide hydrochloride, N-hydroxysuccinimide and deoxycholic acid in N, N-dimethylformamide, and activating at room temperature for 15-30 min to obtain carboxylated deoxycholic acid; dissolving a zwitterionic starch graft polymer in dimethyl sulfoxide, adding deoxycholic acid activated by carboxyl into the zwitterionic starch graft polymer solution with the aid of an ultrasonic field, and stirring and reacting at the temperature of 45-70 ℃ for 6-48 hours; placing the reaction solution in a dialysis bag, dialyzing in a mixed solution of water and methanol, dialyzing in ultrapure water, and freeze-drying the dialyzate to obtain the corn starch graft polymer;
s3, preparing the adriamycin starch grafted polymer micelle: dissolving the corn starch graft polymer prepared in the step S2 in water to prepare a corn starch graft polymer micelle; dissolving doxorubicin hydrochloride and triethylamine in dimethyl sulfoxide, and stirring at room temperature in a dark place for 2-8 hours; adding the doxorubicin hydrochloride solution into the corn starch grafted polymer micelle under the stirring condition, and stirring for 12-24 hours in a dark place; and (3) putting the reaction solution into a dialysis bag, dialyzing the reaction solution in ultrapure water, and freeze-drying the dialyzate to obtain the adriamycin corn starch grafted polymer micelle.
Preferably, the mol/mass ratio of the corn starch to the sulfobetaine is 1mmol: 0.2-1.6 g; the molar ratio of the 1-ethyl- (3-dimethylaminopropyl) -carbodiimide hydrochloride to the N-hydroxysuccinimide to the deoxycholic acid is 1.2:0.6: 0.1-1.0; the mol/mass ratio of the deoxycholic acid to the zwitterionic starch graft polymer is 0.1-1.0 mmol:200 mg; the substitution degree of sulfobetaine on the corn starch graft polymer is regulated and controlled to be 0.09-0.26 by controlling the use amounts of sulfobetaine and deoxycholic acid, and the substitution degree of deoxycholic acid is regulated and controlled to be 0.07-0.25, so that the effects of regulating the particle size of the micelle and improving the drug-loading rate and the encapsulation rate of the micelle are achieved.
Preferably, the concentration of the corn starch graft polymer micelle prepared by dissolving the corn starch graft polymer in water in the step S3 is 1-5 mg/mL.
Preferably, the mass ratio of the doxorubicin hydrochloride to the corn starch graft polymer is 10-30%.
Preferably, the molar ratio of the doxorubicin hydrochloride to the triethylamine is 1: 3-5.
Compared with the prior art, the invention has the following beneficial results:
(1) the micelle prepared by the method has the particle size of less than 200nm, the drug-loading rate of 5-16 percent and the encapsulation rate of 59-80 percent.
(2) The sulfobetaine adopted as the raw material is a natural protein-resistant adsorbing material, and the corn starch and the deoxycholic acid have the characteristics of safety, no toxic or side effect, good biocompatibility, biodegradability and the like.
(3) The preparation method provided by the invention is simple to operate, stable in process, green and environment-friendly, and low in manufacturing cost.
Drawings
FIG. 1 is an infrared spectrum diagram in which CST, SB-CST-DCA and CB-CST represent the infrared spectra of corn starch, corn starch graft polymer and zwitterionic starch graft polymer, respectively;
FIG. 2 is a Transmission Electron Microscope (TEM) observation image of a corn starch graft polymer forming micelles in an aqueous solution.
Detailed Description
Example 1: synthesis of corn starch graft polymer
S1, synthesis of a zwitterionic starch graft polymer: dissolving 1mmol of corn starch in 3mL of ultrapure water, dropwise adding 3mL of 40 wt% sodium hydroxide solution, and stirring at 40 ℃ for reaction for 0.5h to obtain an alkalized starch suspension; dissolving 0.2g of sulfobetaine in 20mL of water, adding the solution into the alkalized starch suspension, and stirring and reacting for 0.5h at 40 ℃; neutralizing the reaction system to be neutral by using glacial acetic acid, precipitating by using methanol, centrifuging to obtain a precipitate, and freeze-drying to obtain a zwitterionic starch graft polymer;
s2, synthesis of a corn starch graft polymer: dissolving 1.2mmol of 1-ethyl- (3-dimethylaminopropyl) -carbodiimide hydrochloride, 0.6mmol of N-hydroxysuccinimide and 0.1mmol of deoxycholic acid in 5mL of N, N-dimethylformamide, and activating at room temperature for 15min to obtain carboxyl activated deoxycholic acid; dissolving 200mg of zwitterionic starch graft polymer in 20mL of dimethyl sulfoxide, dropwise adding deoxycholic acid activated by carboxyl into the zwitterionic starch graft polymer solution under the assistance of an ultrasonic field, and stirring and reacting for 6 hours at 45 ℃; and (3) putting the reaction solution into a dialysis bag, dialyzing in a mixed solution of water and methanol (the volume ratio of the water to the methanol is 1:1) for 3 days, dialyzing in ultrapure water for 2 days, and freeze-drying the dialyzate to obtain the corn starch graft polymer.
The corn starch graft polymer prepared in this example had a degree of substitution of sulfobetaine of 0.09 and a degree of substitution of deoxycholic acid of 0.07.
Example 2: synthesis of corn starch graft polymer
S1, synthesis of a zwitterionic starch graft polymer: dissolving 1mmol of corn starch in 3mL of ultrapure water, dropwise adding 3mL of 40 wt% sodium hydroxide solution, and stirring at 50 ℃ for reaction for 1h to obtain an alkalized starch suspension; dissolving 0.4g of sulfobetaine in 3mL of water, adding the solution into the alkalized starch suspension, and stirring and reacting for 5 hours at 60 ℃; neutralizing the reaction system to be neutral by using glacial acetic acid, precipitating by using methanol, centrifuging to obtain a precipitate, and freeze-drying to obtain the amphoteric ion starch graft polymer;
s2, synthesis of a corn starch graft polymer: dissolving 1-ethyl- (3-dimethylaminopropyl) -carbodiimide hydrochloride (1.2 mmol), N-hydroxysuccinimide (0.6 mmol) and deoxycholic acid (0.3 mmol) in N, N-dimethylformamide (5 mL), and activating at room temperature for 20min to obtain carboxyl-activated deoxycholic acid; dissolving 200mg of zwitterionic starch graft polymer in 20mL of dimethyl sulfoxide, dropwise adding deoxycholic acid activated by carboxyl into the zwitterionic starch graft polymer solution under the assistance of an ultrasonic field, and stirring and reacting for 24 hours at 50 ℃; and (3) putting the reaction solution into a dialysis bag, dialyzing in a mixed solution of water and methanol (the volume ratio of the water to the methanol is 1:1) for 3 days, dialyzing in ultrapure water for 2 days, and freeze-drying the dialyzate to obtain the corn starch graft polymer.
The corn starch graft polymer prepared in this example had a degree of substitution of sulfobetaine of 0.15 and a degree of substitution of deoxycholic acid of 0.13.
Example 3: synthesis of corn starch graft polymer
S1, synthesis of a zwitterionic starch graft polymer: dissolving 1mmol of corn starch in 3mL of ultrapure water, dropwise adding 3mL of 40 wt% sodium hydroxide solution, and stirring at 70 ℃ for reaction for 1.5h to obtain an alkalized starch suspension; dissolving 1.6g of sulfobetaine in 3mL of water, adding the sulfobetaine into the alkalized starch suspension, and stirring and reacting for 8 hours at 70 ℃; neutralizing the reaction system to be neutral by using glacial acetic acid, precipitating by using methanol, centrifuging to obtain a precipitate, and freeze-drying to obtain the amphoteric ion starch graft polymer;
s2, synthesis of a corn starch graft polymer: dissolving 1.2mmol of 1-ethyl- (3-dimethylaminopropyl) -carbodiimide hydrochloride, 0.6mmol of N-hydroxysuccinimide and 1mmol of deoxycholic acid in 5mL of N, N-dimethylformamide, and activating at room temperature for 30min to obtain carboxyl activated deoxycholic acid; dissolving 200mg of zwitterionic starch graft polymer in 20mL of dimethyl sulfoxide, dropwise adding deoxycholic acid activated by carboxyl into the zwitterionic starch graft polymer solution under the assistance of an ultrasonic field, and stirring and reacting for 48 hours at 70 ℃; and (3) putting the reaction solution into a dialysis bag, dialyzing in a mixed solution of water and methanol (the volume ratio of the water to the methanol is 1:1) for 3 days, dialyzing in ultrapure water for 2 days, and freeze-drying the dialyzate to obtain the corn starch graft polymer.
The corn starch graft polymer prepared in this example had a degree of substitution of sulfobetaine of 0.26 and a degree of substitution of deoxycholic acid of 0.25.
Structural characterization of the corn starch graft polymers prepared in examples 1, 2, 3
Under the action of a carbodiimide catalyst, carboxyl on deoxycholic acid can be used as an activating group for chemical grafting reaction and is grafted to a main chain of corn starch to obtain the amphiphilic corn starch graft polymer. In addition, the sulfobetaine is a natural protein-resistant adsorption material, and is grafted to the corn starch main chain, so that the hydrophilicity of the corn starch can be obviously improved, the circulation time of the micelle in vivo is prolonged, and the aim of efficiently treating cancers is fulfilled. The corn starch graft polymer obtained in example 1 was subjected to structural analysis using fourier transform infrared spectroscopy.
As shown in FIG. 1, the infrared spectra of CST, SB-CST-DCA and CB-CST represent 1473cm in SB-CST for corn starch, corn starch graft polymer and zwitterionic starch graft polymer, respectively-1And 1205cm-1Two new characteristic peaks appear due to asymmetric stretching vibration of the N-C and S ═ O bonds in the zwitterionic groups; scheme at SB-CST-DCAStretching vibration at 1739 of C ═ O, indicating the formation of a new ester linkage between the carboxyl group of deoxycholic acid and the hydroxyl group of corn starch. All of these evidence support the successful synthesis of SB-CST-DCA. The structural characterization results of examples 2 and 3 were similar to those of example 1.
Micellar Structure characterization of the corn starch graft polymers prepared in examples 1, 2, and 3
10mg of the corn starch graft polymer obtained in example 1 was dissolved in 10mL of a phosphate buffer solution having a pH of 7.4, and the resulting solution was subjected to ultrasonic probe treatment to obtain a micellar solution having a concentration of 1 mg/mL; and testing the morphology of the micelle by adopting a transmission electron microscope under the following test conditions: the applied voltage was 200 kV.
Fig. 2 is a transmission electron microscope image of the corn starch grafted polymer micelle prepared in this example 1, and as can be seen from fig. 2, the prepared micelle has a regular spherical structure, uniform size and good morphology structure. The structural characterization results of examples 2 and 3 were similar to those of example 1.
Example 4: preparation of adriamycin corn starch graft polymer micelle (according to the feeding ratio of the theoretical drug-loading rate of 30 percent)
Weighing 100mg of the corn starch graft polymer synthesized in the embodiment 1, and adding 100mL of ultrapure water for dissolving to obtain the corn starch graft polymer micelle with the concentration of 1 mg/mL; dissolving 30mg of doxorubicin hydrochloride and triethylamine in dimethyl sulfoxide according to a molar ratio of 1:3, and stirring at room temperature in a dark place for 2 hours; adding the doxorubicin hydrochloride solution into the corn starch graft polymer micelle, and stirring for 12 hours in a dark place; and putting the reaction solution into a dialysis bag, dialyzing the reaction solution in ultrapure water for 24 hours, and freeze-drying the dialyzate to obtain the adriamycin corn starch grafted polymer micelle.
The micelle obtained in the embodiment has the particle size of less than 200nm, the drug loading rate of 16 percent and the encapsulation rate of 80 percent.
Example 5: preparation of adriamycin corn starch graft polymer micelle (according to the feeding ratio of the theoretical drug-loading rate of 20 percent)
Weighing 50mg of the corn starch graft polymer synthesized in the example 1, and adding 25mL of ultrapure water for dissolving to obtain a corn starch graft polymer micelle with the concentration of 2 mg/mL; dissolving 10mg of doxorubicin hydrochloride and triethylamine in dimethyl sulfoxide according to a molar ratio of 1:4, and stirring at room temperature in a dark place for 4 hours; adding the doxorubicin hydrochloride solution into the corn starch graft polymer micelle, and stirring for 18 hours in a dark place; and putting the reaction solution into a dialysis bag, dialyzing the reaction solution in ultrapure water for 24 hours, and freeze-drying the dialyzate to obtain the adriamycin corn starch grafted polymer micelle.
The micelle obtained in the embodiment has the particle size of less than 200nm, the drug loading rate of 9 percent and the encapsulation rate of 61 percent.
Example 6: preparation of adriamycin corn starch graft polymer micelle (according to the feeding ratio of the theoretical drug-loading rate of 10 percent)
Weighing 50mg of the corn starch graft polymer synthesized in the example 1, and adding 10mL of ultrapure water for dissolving to obtain a corn starch graft polymer micelle with the concentration of 5 mg/mL; dissolving 5mg of doxorubicin hydrochloride and triethylamine in dimethyl sulfoxide according to a molar ratio of 1:5, and stirring at room temperature in a dark place for 8 hours; adding the doxorubicin hydrochloride solution into the corn starch graft polymer micelle, and stirring for 24 hours in a dark place; and putting the reaction solution into a dialysis bag, dialyzing the reaction solution in ultrapure water for 24 hours, and freeze-drying the dialyzate to obtain the adriamycin corn starch grafted polymer micelle.
The micelle obtained in the embodiment has the particle size of less than 200nm, the drug loading rate of 5 percent and the encapsulation rate of 59 percent.
Claims (6)
1. A preparation method of an adriamycin corn starch grafted polymer micelle is characterized by comprising the following steps:
s1, synthesis of a zwitterionic starch graft polymer: preparing the corn starch into an alkalized starch suspension by using a sodium hydroxide solution, and stirring and reacting for 0.5-1.5 h at the temperature of 40-70 ℃; dissolving sulfobetaine in water, adding the solution into the alkalized starch suspension, and stirring and reacting for 0.5-8.0 h at 40-70 ℃; neutralizing the reaction system to be neutral by using glacial acetic acid, precipitating by using methanol, centrifuging to obtain a precipitate, and freeze-drying to obtain the amphoteric ion starch graft polymer;
s2, synthesis of a corn starch graft polymer: dissolving 1-ethyl- (3-dimethylaminopropyl) -carbodiimide hydrochloride, N-hydroxysuccinimide and deoxycholic acid in N, N-dimethylformamide, and activating at room temperature for 15-30 min to obtain carboxylated deoxycholic acid; dissolving a zwitterionic starch graft polymer in dimethyl sulfoxide, adding deoxycholic acid activated by carboxyl into the zwitterionic starch graft polymer solution with the aid of an ultrasonic field, and stirring and reacting at the temperature of 45-70 ℃ for 6-48 hours; placing the reaction solution in a dialysis bag, dialyzing in a mixed solution of water and methanol, dialyzing in ultrapure water, and freeze-drying the dialyzate to obtain the corn starch graft polymer;
s3, preparing the adriamycin starch grafted polymer micelle: dissolving a corn starch graft polymer in water to prepare a corn starch graft polymer micelle, dissolving doxorubicin hydrochloride and triethylamine in dimethyl sulfoxide, and stirring at room temperature in a dark place for 2-8 hours; adding the doxorubicin hydrochloride solution into the corn starch grafted polymer micelle under the stirring condition, and stirring for 12-24 hours in a dark place; and (3) putting the reaction solution into a dialysis bag, dialyzing the reaction solution in ultrapure water, and freeze-drying the dialyzate to obtain the adriamycin corn starch grafted polymer micelle.
2. The preparation method according to claim 1, wherein the molar/mass ratio of the corn starch to the sulfobetaine is 1mmol: 0.2-1.6 g; the molar ratio of the 1-ethyl- (3-dimethylaminopropyl) -carbodiimide hydrochloride to the N-hydroxysuccinimide to the deoxycholic acid is 1.2:0.6: 0.1-1.0; the mol/mass ratio of the deoxycholic acid to the zwitterionic starch graft polymer is 0.1-1.0 mmol:200 mg; the substitution degree of sulfobetaine on the corn starch graft polymer is controlled to be 0.09-0.26 by controlling the use amounts of sulfobetaine and deoxycholic acid, and the substitution degree of deoxycholic acid is controlled to be 0.07-0.25.
3. The method of claim 1, wherein the corn starch graft polymer micelle prepared by dissolving the corn starch graft polymer in water in the step S3 has a concentration of 1-5 mg/mL.
4. The preparation method according to claim 1, wherein the mass ratio of the doxorubicin hydrochloride to the corn starch graft polymer is 10% to 30%.
5. The preparation method according to claim 1, wherein the molar ratio of the doxorubicin hydrochloride to the triethylamine is 1: 3-5.
6. The adriamycin corn starch grafted polymer micelle prepared by the preparation method of any one of claims 1 to 5.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050191359A1 (en) * | 2001-09-28 | 2005-09-01 | Solubest Ltd. | Water soluble nanoparticles and method for their production |
| CN104004134A (en) * | 2014-05-30 | 2014-08-27 | 西华大学 | Preparation method of grain size controllable monodisperse nano starch microspheres |
| CN104434792A (en) * | 2013-09-12 | 2015-03-25 | 中国科学院深圳先进技术研究院 | Polymer micelle, preparation method thereof, antitumor pharmaceutical composition, preparation and preparation method thereof |
-
2020
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050191359A1 (en) * | 2001-09-28 | 2005-09-01 | Solubest Ltd. | Water soluble nanoparticles and method for their production |
| CN104434792A (en) * | 2013-09-12 | 2015-03-25 | 中国科学院深圳先进技术研究院 | Polymer micelle, preparation method thereof, antitumor pharmaceutical composition, preparation and preparation method thereof |
| CN104004134A (en) * | 2014-05-30 | 2014-08-27 | 西华大学 | Preparation method of grain size controllable monodisperse nano starch microspheres |
Non-Patent Citations (4)
| Title |
|---|
| JINLONG YANG ET AL.: "Novel self-assembled amphiphilic mPEGylated starch-deoxycholic acid polymeric micelles with pH-response for anticancer drug delivery", 《RSC ADV.》 * |
| LEI YE ET AL.: "Zwitterionic-Modified Starch-Based Stealth Micelles for Prolonging Circulation Time and Reducing Macrophage Response", 《ACS APPL. MATER. INTERFACES》 * |
| LINQI YUN ET AL.: "Dual-modified starch micelles as a promising nanocarrier for doxorubicin", 《INT J BIOL MACROMOL.》 * |
| LINQI YUN ET AL.: "Structure and properties of corn starch synthesized by using sulfobetaine and deoxycholic acid", 《INT J BIOL MACROMOL.》 * |
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