CN109464423B - Calcium alginate-chitosan microsphere and preparation method thereof, medicine-carrying calcium alginate-chitosan and preparation method thereof - Google Patents
Calcium alginate-chitosan microsphere and preparation method thereof, medicine-carrying calcium alginate-chitosan and preparation method thereof Download PDFInfo
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Abstract
The invention provides a calcium alginate-chitosan microsphere and a preparation method thereof, and a medicine-carrying calcium alginate-chitosan microsphere and a preparation method thereof, relating to the technical field of medicine carriers, wherein the preparation method of the calcium alginate-chitosan microsphere comprises the following steps: the calcium alginate-chitosan microspheres are prepared by the electrostatic spraying method, the working procedure is simple, the operation is convenient, the particle size of the microspheres is uniform, the particle size is distributed in 20-50 mu m, and the sustained and controlled release of the drug is easier to accurately control after the drug is encapsulated.
Description
Technical Field
The invention relates to the technical field of drug carriers, in particular to a calcium alginate-chitosan microsphere and a preparation method thereof, a drug-loaded calcium alginate-chitosan and a preparation method thereof.
Background
With the intensive research on drug carrier systems, in recent years, microsomal drug controlled release systems such as microcapsules/spheres have been developed rapidly and are widely used clinically.
The existing methods for preparing microsphere drug carriers mainly comprise a precipitation method and an emulsification method, and the methods have the defects of complicated working procedures, wide microsphere particle size distribution, easy formation of microspheres with larger particle sizes, influence on the overall uniformity of the drug carriers and difficulty in accurate control in the drug sustained-release stage.
In view of the above, the present invention is particularly proposed.
Disclosure of Invention
The invention aims to provide a preparation method of calcium alginate-chitosan microspheres, which aims to solve the technical problems that the preparation process of microsphere drug carriers by adopting a precipitation method and an emulsification method is complicated, the particle size distribution of the microspheres is wide, microspheres with larger particle sizes are easy to form, the integral uniformity of the drug carriers is influenced, and the precise control is difficult in the drug sustained-release stage.
The preparation method of the calcium alginate-chitosan microspheres provided by the invention comprises the following steps: and (3) spraying the sodium alginate solution into the mixed solution of chitosan and calcium chloride through electrostatic spraying to obtain the calcium alginate-chitosan microspheres.
Further, the mass concentration of the sodium alginate solution is 1.5-4%, preferably 2-3%.
Further, in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.05-0.2%, preferably 0.08-0.12%;
and/or the mass concentration of the calcium chloride is 1-3%, preferably 1.5-2.5%.
Further, the spraying speed of the sodium alginate solution is 3-7mL/h, preferably 4.5-5.5 mL/h;
preferably, the sodium alginate solution is sprayed into the mixed solution of chitosan and calcium chloride by electrostatic spraying by using a high-voltage electrostatic sprayer.
The invention also aims to provide a calcium alginate-chitosan microsphere which is obtained according to the preparation method of the calcium alginate-chitosan microsphere provided by the invention;
preferably, the particle size of the calcium alginate-chitosan microspheres is 20-50 μm.
The invention also aims to provide a drug-loaded calcium alginate-chitosan microsphere, which comprises a drug and the calcium alginate-chitosan microsphere provided by the invention, wherein the drug is coated in the calcium alginate-chitosan microsphere;
preferably, the particle size of the drug-loaded calcium alginate-chitosan microspheres is 20-50 μm.
The fourth purpose of the invention is to provide a preparation method of the drug-loaded calcium alginate-chitosan microspheres, which comprises the following steps: and spraying the mixed solution of the medicine and the sodium alginate into the mixed solution of the chitosan and the calcium chloride through electrostatic spraying to obtain the medicine-carrying calcium alginate-chitosan microspheres.
Further, in the mixed solution of the medicine and the sodium alginate, the mass concentration of the sodium alginate is 1.5-4%, preferably 2-3%;
and/or the mass concentration of the medicine in the mixed solution of the medicine and the sodium alginate is 0.5-1.5%, preferably 0.8-1.2%.
Further, in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.05-0.2%, preferably 0.08-0.12%;
and/or the mass concentration of the calcium chloride is 1-3%, preferably 1.5-2.5%.
Further, the ejection speed of the mixed solution of the medicine and the sodium alginate is 3-7mL/h, and preferably 4.5-5.5 mL/h;
preferably, the sodium alginate solution is sprayed into the mixed solution of chitosan and calcium chloride by using a high-voltage electrostatic sprayer.
The calcium alginate-chitosan microspheres provided by the invention are prepared by an electrostatic spraying method, the process is simple, the operation is convenient, the particle size of the microspheres is uniform, and the particle size distribution is 20-50 mu m, so that the sustained and controlled release of the drug is easier to accurately control after the drug is encapsulated.
The calcium alginate-chitosan microspheres provided by the invention have uniform particle size, the particle size is distributed in the range of 20-50 mu m, and after the calcium alginate-chitosan microspheres are coated with the calcium alginate-chitosan microspheres, the sustained and controlled release of the drug is easier to accurately control.
The drug-loaded calcium alginate-chitosan microsphere provided by the invention has the advantages of uniform particle size, particle size distribution of 20-50 mu m, high drug encapsulation rate, good sustained and controlled release effect and capability of effectively improving the treatment effect of the drug.
Drawings
FIG. 1 is an optical microscope photograph of calcium alginate-chitosan microspheres provided in example 5;
fig. 2 is an optical micrograph of the drug-loaded calcium alginate-chitosan microspheres provided in example 14;
FIG. 3 is an SEM image of calcium alginate-chitosan microspheres provided in example 5;
fig. 4 is an SEM image of the drug-loaded calcium alginate-chitosan microspheres provided in example 14;
FIG. 5 is a graph showing the relationship between cumulative release amount and release time of the drug-loaded calcium alginate-chitosan provided in example 14;
FIG. 6 is a graph of absorbance versus storage time for calcium alginate-chitosan and naringenin drug loaded as provided in example 14.
Detailed Description
The technical solutions of the present invention will be described clearly and completely below, and it should be apparent that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
According to one aspect of the invention, the invention provides a preparation method of calcium alginate-chitosan microspheres, which comprises the following steps: and (3) electrostatically spraying the sodium alginate solution into the mixed solution of chitosan and calcium chloride to obtain the calcium alginate-chitosan microspheres.
According to the preparation method of the calcium alginate-chitosan microspheres, provided by the invention, the sodium alginate solution is sprayed into the mixed solution of chitosan and calcium chloride through electrostatic spraying to prepare the microspheres, the process is simple, the operation is convenient, the particle size of the microspheres is uniform, and the particle size is distributed in the range of 20-50 microns, so that the sustained and controlled release of the drug is easier to accurately control after the drug is encapsulated.
In a preferred embodiment of the invention, the sodium alginate solution has a mass concentration of 1.5-4%.
The calcium alginate-chitosan microsphere drug carrier with high drug encapsulation rate is obtained by controlling the mass concentration of the sodium alginate solution, if the mass solubility of the sodium alginate solution is lower than 1.5%, microspheres with uniform particle size are difficult to prepare, and if the mass concentration of the sodium alginate solution is higher than 4%, the prepared microspheres have too large particle size and are not suitable to be used as the drug carrier.
In a preferred embodiment of the invention, the sodium alginate solution has a typical but non-limiting mass concentration of, for example, 1.5%, 1.8%, 2%, 2.2%, 2.5%, 2.8%, 3%, 3.2%, 3.5%, 3.8% or 4%.
In a preferred embodiment of the present invention, in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.05-0.2%,
in a preferred embodiment of the present invention, the concentration of chitosan in the mixed solution of chitosan and calcium chloride is controlled to control the particle size and the particle size distribution of the prepared calcium alginate-chitosan microspheres.
In a preferred embodiment of the present invention, the chitosan is typically, but not limited to, 0.05%, 0.08%, 0.1%, 0.12%, 0.15%, 0.18%, or 0.2% by mass of the mixed solution of chitosan and calcium chloride.
In a preferred embodiment of the present invention, the calcium chloride is present in the mixed solution of chitosan and calcium chloride at a concentration of 1 to 3% by mass.
In the invention, calcium chloride is used for carrying out calcium ion exchange with sodium alginate to obtain gelatinous calcium alginate.
In a preferred embodiment of the invention, the typical but non-limiting mass concentration of calcium chloride in the mixed solution of chitosan and calcium chloride is, for example, 1%, 1.2%, 1.5%, 1.8%, 2%, 2.2%, 2.5%, 2.8% or 3%.
In a preferred embodiment of the invention, the sodium alginate solution is sprayed at a rate of 3-7 mL/h.
In a preferred embodiment of the invention, the sodium alginate solution is sprayed at a typical but non-limiting spray rate of, for example, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5 or 7 mL/h.
By controlling the injection speed of the sodium alginate solution, the prepared calcium alginate-chitosan microspheres have more uniform particle size and higher drug encapsulation efficiency.
In a preferred embodiment of the invention, the sodium alginate solution is sprayed into the mixed solution of chitosan and calcium chloride by electrostatic spraying by using a high-voltage electrostatic sprayer.
In a further preferred embodiment of the invention, the voltage of the high-voltage electrostatic atomizer is from 12 to 20kV, preferably from 14 to 18 kV.
In a preferred embodiment of the invention, typical but not limiting voltages for high voltage electrostatic sprayers are, for example, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5 or 18 kV.
The voltage of the high-voltage electrostatic sprayer is controlled to be 12-20kV, so that microspheres with uniform particle size and particle size of 15-60 mu m are prepared.
According to a second aspect of the invention, the invention provides calcium alginate-chitosan microspheres obtained by the preparation method provided by the first aspect of the invention.
The calcium alginate-chitosan microspheres provided by the invention have uniform particle size, the particle size is distributed in the range of 20-50 mu m, and after the calcium alginate-chitosan microspheres are coated with the calcium alginate-chitosan microspheres, the sustained and controlled release of the drug is easier to accurately control.
In a preferred embodiment of the present invention, the particle size of the calcium alginate-chitosan microspheres is 20-50 μm.
In a preferred embodiment of the invention, the calcium alginate-chitosan microspheres have a typical, but not limiting, particle size of e.g. 20, 22, 25, 28, 30, 35, 40, 45 or 50 μm.
According to a third aspect of the invention, the invention provides a drug-loaded calcium alginate-chitosan microsphere, which comprises a drug and the calcium alginate-chitosan microsphere provided by the invention, wherein the drug is coated in the calcium alginate-chitosan microsphere.
The drug-loaded calcium alginate-chitosan microsphere provided by the invention has the advantages of uniform particle size, particle size distribution of 20-50 mu m, high drug encapsulation rate, good sustained and controlled release effect and capability of effectively improving the treatment effect of the drug.
In a preferred embodiment of the invention, the particle size of the drug-loaded calcium alginate-chitosan microspheres is 20-50 μm.
In a preferred embodiment of the invention, the drug-loaded calcium alginate-chitosan microspheres have a typical, but not limiting, particle size of e.g. 20, 22, 25, 28, 30, 35, 40, 45 or 50 μm.
According to a fourth aspect of the invention, the invention provides a preparation method of a drug-loaded calcium alginate-chitosan microsphere, which comprises the following steps: and spraying the mixed solution of the medicine and the sodium alginate into the mixed solution of the chitosan and the calcium chloride through electrostatic spraying to obtain the medicine-carrying chitosan microsphere.
The drug-loaded calcium alginate-chitosan microsphere provided by the invention is prepared by an electrostatic spraying method, has simple process and convenient operation, has uniform microsphere particle size and high drug encapsulation rate, and is easy to accurately control the sustained and controlled release behavior of the drug.
In a preferred embodiment of the present invention, the mass concentration of sodium alginate in the mixed solution of the drug and sodium alginate is 1.5-4%.
The medicine-carrying calcium alginate-chitosan microspheres with high medicine encapsulation efficiency are obtained by controlling the mass concentration of sodium alginate in a mixed solution of a medicine and sodium alginate, if the mass solubility of the sodium alginate is lower than 1.5%, the microspheres with uniform particle size are difficult to prepare, and the medicine encapsulation efficiency is low, and if the mass concentration of the sodium alginate is higher than 4%, the particle size of the prepared microspheres is too large, so that the use requirement of a medicine delivery system cannot be met.
In a preferred embodiment of the invention, the sodium alginate is typically, but not limited to, in a mixed solution of the drug and the sodium alginate, at a mass concentration of 1.5%, 1.8%, 2%, 2.2%, 2.5%, 2.8%, 3%, 3.2%, 3.5%, 3.8% or 4%.
In a preferred embodiment of the present invention, the mass concentration of the drug in the mixed solution of the drug and sodium alginate is 0.5-1.5%.
In a preferred embodiment of the invention, the drug is typically, but not limited to, in a mixed solution of the drug and sodium alginate, at a mass concentration of 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4 or 1.5%.
In a preferred embodiment of the present invention, in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.05-0.2%,
in a preferred embodiment of the invention, the concentration of chitosan in the mixed solution of chitosan and calcium chloride is controlled to control the particle size of the prepared drug-loaded calcium alginate-chitosan microspheres to be 20-50 μm and the particle size distribution to be uniform.
In a preferred embodiment of the present invention, the chitosan is typically, but not limited to, 0.05%, 0.08%, 0.1%, 0.12%, 0.15%, 0.18%, or 0.2% by mass of the mixed solution of chitosan and calcium chloride.
In a preferred embodiment of the present invention, the calcium chloride is present in the mixed solution of chitosan and calcium chloride at a concentration of 1 to 3% by mass.
In the invention, calcium chloride is used for carrying out calcium ion exchange with sodium alginate to obtain gelatinous calcium alginate.
In a preferred embodiment of the invention, the typical but non-limiting mass concentration of calcium chloride in the mixed solution of chitosan and calcium chloride is, for example, 1%, 1.2%, 1.5%, 1.8%, 2%, 2.2%, 2.5%, 2.8% or 3%.
In a preferred embodiment of the invention, the typical but non-limiting spray rate of the mixed solution of the drug and sodium alginate is, for example, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5 or 7 mL/h.
By controlling the spraying speed of the medicine and the sodium alginate solution, the prepared medicine calcium alginate-chitosan microspheres have more uniform grain diameter and higher medicine encapsulation efficiency.
In a preferred embodiment of the present invention, a mixed solution of the drug and sodium alginate is sprayed into a mixed solution of chitosan and calcium chloride by electrostatic spraying using a high-voltage electrostatic sprayer.
In a further preferred embodiment of the invention, the voltage of the high-voltage electrostatic atomizer is from 12 to 20kV, preferably from 14 to 18 kV.
In a preferred embodiment of the invention, typical but not limiting voltages for high voltage electrostatic sprayers are, for example, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5 or 18 kV.
The drug-loaded microspheres with uniform particle size and 15-60 mu m particle size are prepared by controlling the voltage of a high-voltage electrostatic sprayer to be 12-20 kV.
In a preferred embodiment of the invention, the drug-loaded calcium alginate-chitosan is prepared by the following steps:
(a) spraying the mixed solution of the medicine and the sodium alginate into the mixed solution of the chitosan and the calcium chloride by an electrostatic spraying device;
(b) and (b) centrifuging the solution obtained in the step (a), removing supernatant, washing with deionized water for several times, and drying to obtain the calcium alginate-chitosan microspheres.
In the present invention, drugs include, but are not limited to, naringenin and barbaloin.
The technical solution provided by the present invention is further described below with reference to examples and comparative examples.
Example 1
The embodiment provides a calcium alginate-chitosan microsphere, and the preparation method comprises the following steps:
(1) preparing a sodium alginate solution by using water as a solvent, wherein the mass concentration of the sodium alginate is 1.5%;
(2) preparing a mixed solution of chitosan and calcium chloride by taking acetic acid as a solvent, wherein the concentration of the chitosan is 0.2%, and the concentration of the calcium chloride is 1%;
(3) spraying a sodium alginate solution into a mixed solution of chitosan and calcium chloride by electrostatic spraying at a spraying speed of 4.5 mL/h;
(4) and (4) centrifuging the solution in the step (3) at the speed of 5000 r/min, removing supernatant, then washing for 3 times by using deionized water to obtain calcium alginate-chitosan microsphere suspension, and freeze-drying to obtain the calcium alginate-chitosan microsphere.
Example 2
The embodiment provides a calcium alginate-chitosan microsphere, and the preparation method is different from that of the embodiment 1 in that in the step (1), the mass concentration of the sodium alginate solution is 4%; in the step (2), in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.05%, and the mass concentration of calcium chloride is 3%.
Example 3
The embodiment provides a calcium alginate-chitosan microsphere, and the preparation method is different from that of the embodiment 1 in that in the step (1), the mass concentration of the sodium alginate solution is 2%; in the step (2), in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.1%, and the mass concentration of calcium chloride is 1.5%.
Example 4
The embodiment provides a calcium alginate-chitosan microsphere, and the preparation method is different from that of the embodiment 1 in that in the step (1), the mass concentration of the sodium alginate solution is 3%; in the step (2), in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.1%, and the mass concentration of calcium chloride is 2.5%.
Example 5
The embodiment provides a calcium alginate-chitosan microsphere, and the preparation method is different from that of the embodiment 1 in that in the step (1), the mass concentration of sodium alginate in the mixed solution of the sodium alginate solution is 2.5%; in the step (2), in the mixed solution of chitosan and calcium chloride, the mass concentration of chitosan is 0.1%, and the mass concentration of calcium chloride is 2%.
Example 6
This example provides a calcium alginate-chitosan microsphere, and the preparation method is different from that in example 5, in step (1), the mass concentration of the sodium alginate solution is 0.5%.
Example 7
This example provides a calcium alginate-chitosan microsphere, and the preparation method is different from that in example 5, in step (1), the mass concentration of the sodium alginate solution is 10%.
Example 8
This example provides a calcium alginate-chitosan microsphere, which is prepared by a method different from that of example 5, in the step (2), the mass concentration of chitosan in the mixed solution of chitosan and calcium chloride is 0.01%.
Example 9
This example provides a calcium alginate-chitosan microsphere, which is prepared by a method different from that of example 5, in the step (2), the mass concentration of chitosan in the mixed solution of chitosan and calcium chloride is 0.5%.
Example 10
Examples 11 to 18
Examples 11 to 18 each provide a drug-loaded calcium alginate-chitosan microsphere, which is prepared by coating naringenin in the calcium alginate-chitosan microspheres as the drug carriers provided in examples 2 to 9, and the preparation method is the same as example 10, and is not repeated herein.
Comparative example 1
The comparative example provides a drug-loaded calcium alginate microsphere, and the preparation method comprises the following steps: the preparation method comprises the steps of spraying a mixed solution of naringenin and sodium alginate into a calcium chloride solution through electrostatic spraying to prepare the naringenin-sodium alginate mixed solution, wherein the mass concentration of the naringenin is 1%, the mass concentration of the sodium alginate is 2.5%, and the mass concentration of the calcium chloride in the calcium chloride solution is 2%, so that the details are not repeated.
Test example 1
The calcium alginate-chitosan microspheres provided in example 5 and the drug-loaded calcium alginate-chitosan microspheres provided in example 15 are subjected to an optical microscope test and a scanning electron microscope test, respectively, and the results are shown in fig. 1-4, wherein fig. 1 is an optical microscope image of the calcium alginate-chitosan microspheres provided in example 5; fig. 2 is an optical microscope image of the drug-loaded calcium alginate-chitosan microspheres provided in example 14; fig. 3 is an SEM image of the calcium alginate-chitosan microspheres provided in example 5, and fig. 4 is an SEM image of the drug-loaded calcium alginate-chitosan microspheres provided in example 14. As can be seen from fig. 1 and fig. 2, the calcium alginate-chitosan microspheres and the drug-loaded calcium alginate-chitosan microspheres have uniform particle sizes, and the calcium alginate-chitosan microspheres are hollow structures, while the drug-loaded calcium alginate-chitosan microspheres are coated with a substance, which indicates that the drug-loaded calcium alginate-chitosan microspheres provided in example 14 can successfully coat naringenin in the calcium alginate-chitosan microspheres.
As seen from fig. 3, the particle size of the calcium alginate-chitosan microsphere provided in example 5 is uniform and is 20 to 50 μm, and as seen from fig. 4, the drug-loaded calcium alginate-chitosan microsphere provided in example 14 has an obvious core-shell structure, which also indicates that the drug-loaded calcium alginate-chitosan microsphere provided in example 14 can successfully coat naringenin in the calcium alginate-chitosan microsphere.
Test example 2
0.2g of the drug-loaded calcium alginate-chitosan microspheres provided in example 14 is dissolved in 20ml of the PBS solution, the solution is placed in a constant temperature shaking table (37 ℃, 70 r/min), 2 ml of the solution is taken at a specific time, 2 ml of fresh PBS solution is supplemented after absorbance is measured, the release amount of naringenin is calculated through absorbance, a curve is drawn by taking time as an abscissa and taking the accumulated release amount of naringenin as an ordinate, the curve is shown in fig. 5, it can be seen from fig. 5 that the accumulated release amount of naringenin continuously increases along with the increase of time, and naringenin is basically released after 12 hours, which indicates that the drug release time of the drug-loaded calcium alginate-chitosan provided in example 14 of the present invention can reach 12 hours.
Test example 3
12mg of the drug-loaded microspheres provided in examples 10-18 and comparative example 1 were respectively used for drug encapsulation efficiency test, and the results are shown in table 1.
TABLE 1 data sheet of encapsulation efficiency of naringenin by drug-loaded microspheres
Encapsulation efficiency (%) | |
Example 10 | 45.1 |
Example 11 | 56.2 |
Example 12 | 48.3 |
Example 13 | 61.7 |
Example 14 | 72.9 |
Example 15 | 15.5 |
Example 16 | 35.2 |
Example 17 | 27.2 |
Example 18 | 41.2 |
Comparative example 1 | 25.4 |
As shown in the comparison between examples 11 to 18 and comparative example 1 in table 1, the drug encapsulation efficiency of the drug-loaded calcium alginate-chitosan microspheres provided in examples 11 to 18 is significantly higher than that of comparative example 1, which indicates that the drug-loaded calcium alginate-chitosan microspheres provided by the present invention significantly improve the drug encapsulation efficiency through the mutual synergy between calcium alginate and chitosan, thereby effectively improving the therapeutic effect of the drug-loaded microspheres.
As can be seen from comparison between examples 11-14 and examples 15-18, the drug encapsulation efficiency of the drug-loaded microspheres provided in examples 11-14 is significantly higher than that of examples 15-18, which shows that when the drug-loaded microspheres are prepared, when the mass concentration of sodium alginate in the mixed solution of naringenin and sodium alginate is 1.5-4%, the mass concentration of chitosan in the mixed solution of chitosan and calcium chloride is 0.05-0.2%, and the mass concentration of calcium chloride is 1-3%, the drug encapsulation efficiency of the prepared drug-loaded calcium alginate-chitosan microspheres is higher.
Test example 4
The drug-loaded calcium alginate-chitosan microspheres and naringenin provided in example 14 were stored in a refrigerator (20 ℃ below zero), 0.01g of naringenin and 0.02g of drug-loaded calcium alginate-chitosan microspheres were weighed at regular intervals, dissolved in a 10 mPBS solution, and absorbance curves of the naringenin and the drug-loaded calcium alginate-chitosan microspheres were plotted as shown in fig. 6.
As can be seen from FIG. 6, the absorbance of naringenin is basically kept unchanged at the first 36h, and after 36h, the absorbance is obviously reduced, which shows that naringenin is decomposed after being kept for 36h, so that the absorbance is obviously reduced; the absorbance curve of the drug-loaded calcium alginate-chitosan microspheres is kept stable within 60 hours, which shows that the drug-loaded calcium alginate-chitosan microspheres can remarkably improve the stability of naringenin and reduce the decomposition of naringenin.
Test example 5
The calcium alginate-chitosan microspheres provided in example 5 and the drug-loaded calcium alginate-chitosan microspheres provided in example 14 were dissolved in PBS solution respectively to prepare solutions with the same mass concentration, and then the antibacterial rates of the two microspheres were measured respectively, and the results are shown in table 2.
TABLE 2 data sheet of antimicrobial property of microspheres
Escherichia coli inhibitory rate (%) | Staphylococcus aureus inhibitory rate (%) | |
Example 5 | 60.4 | 80.1 |
Example 14 | 86.1 | 91.1 |
As can be seen from table 2, both the calcium alginate-chitosan microspheres provided in example 5 and the drug-loaded calcium alginate-chitosan microspheres provided in example 14 have an obvious bacteriostatic effect, and especially after the drug-loaded calcium alginate-chitosan microspheres provided in example 14 are coated with naringenin, the antibacterial performance is better.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (1)
1. The drug-loaded calcium alginate-chitosan microsphere is characterized in that the preparation method comprises the following steps:
(1) preparing a sodium alginate solution by using water as a solvent, wherein the mass concentration of the sodium alginate is 2.5%, dissolving naringenin in the sodium alginate solution, and the mass concentration of the naringenin is 1%;
(2) preparing a mixed solution of chitosan and calcium chloride by taking acetic acid as a solvent, wherein the concentration of the chitosan is 0.1%, and the concentration of the calcium chloride is 2%;
(3) spraying the mixed solution of naringenin and sodium alginate into the mixed solution of chitosan and calcium chloride by electrostatic spraying at the spraying speed of 4.5 mL/h;
(4) centrifuging the solution in the step (3) at a speed of 5000 r/min, removing supernatant, washing for 3 times by using deionized water to obtain a drug-loaded calcium alginate-chitosan microsphere suspension, and freeze-drying to obtain drug-loaded calcium alginate-chitosan microspheres;
wherein the particle size of the drug-loaded calcium alginate-chitosan microsphere is 20-50 μm.
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