CN113149022B - Silica @ calcium silicate hollow nanosphere and preparation method and application thereof - Google Patents
Silica @ calcium silicate hollow nanosphere and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a silicon dioxide @ calcium silicate hollow nanosphere and a preparation method and application thereof, and relates to the technical field of drug sustained-release microspheres. SiO provided by the invention2@CaSiO3The hollow nanospheres take hollow mesoporous silica nanospheres as core layers and calcium silicate as shell layers; the SiO2@CaSiO3Several hollow nanospheres are distributed on the upper surface of the upper layerAnd the through holes are communicated with the outside, and part of the through holes are communicated with the hollow structure of the nuclear layer. SiO provided by the invention2@CaSiO3The hollow nanosphere has high encapsulation efficiency, high drug loading rate, no toxicity, no harm, good biocompatibility, good degradability in human body and excellent pH response capability at special positions.
Description
Technical Field
The invention relates to the technical field of drug sustained-release microspheres, in particular to a silicon dioxide @ calcium silicate hollow nanosphere and a preparation method and application thereof.
Background
Calcium silicate (CaSiO)3Calcium Silicate) is an important inorganic component of human bones and teeth, and is widely applied to the research of drug sustained-release carriers due to good biocompatibility and biosafety. CaSiO in contrast to viral vectors3The inorganic carrier has no immunogenicity, and does not cause immune response to organisms; meanwhile, CaSiO3Has good biodegradability, and the degradation period of the biodegradable material is closely related to the physical and chemical properties of the material.
Chinese patent CN110693851A discloses mesoporous silica drug-loaded nanoparticles, a preparation method and an application thereof, wherein mesoporous silica is used as a drug-loaded carrier, a polydopamine layer is wrapped outside the mesoporous silica carrier, and a tumor-oriented penetration peptide iRGD and poly (2-ethyl-2-oxazoline) are connected through Schiff base addition reaction for loading anticancer drugs, but the material stability is poor, and the sustained-release effect is not ideal after the drugs are basically released within 24 hours. Chinese patent CN109589418A discloses a Schiff base copolymer coated mesoporous silica drug-loaded nanoparticle with pH responsiveness, and a preparation method and application thereof.
Disclosure of Invention
The invention aims to provide a silicon dioxide @ calcium silicate hollow nanosphere and a preparation method and application thereof, and the SiO provided by the invention2@CaSiO3The hollow nanosphere has high encapsulation efficiency, high drug loading rate, no toxicity, no harm, good biocompatibility, good slow release effect, good degradability in human body, and excellent pH response capability at special parts (in acidic body fluid environment such as human stomach).
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides SiO2@CaSiO3The hollow nanospheres take hollow mesoporous silica nanospheres as core layers and calcium silicate as shell layers; the SiO2@CaSiO3The hollow nanospheres are distributed with a plurality of through holes which are communicated with the outside, and part of the through holes are communicated with the hollow structure of the core layer.
Preferably, the SiO2@CaSiO3The particle size of the hollow nanospheres is 300-500 nm.
Preferably, the diameter of the hollow structure of the nuclear layer is 200-300 nm; the aperture of the through hole is 4-6 nm.
Preferably, the calcium silicate is SiO in mass2@CaSiO35-10% of the total mass of the hollow nanospheres.
The invention provides the SiO in the technical scheme2@CaSiO3The preparation method of the hollow nanosphere comprises the following steps:
dispersing hollow mesoporous silica nanospheres in water to obtain silica nanosphere dispersion liquid;
mixing the silicon dioxide nanosphere dispersion liquid with a surfactant to obtain a modified silicon dioxide nanosphere dispersion liquid;
mixing the modified silicon dioxide nanosphere dispersion liquid with an alkaline substance, adjusting the pH value of a system to be 12-13, adding a calcium source, and carrying out a precipitation reaction to obtain SiO2@CaSiO3Hollow nanospheres.
Preferably, the mass ratio of the surfactant to the hollow mesoporous silica nanospheres is 2-7: 10-20.
Preferably, the mass ratio of the calcium source to the hollow mesoporous silica nanospheres is 6-9: 5-10.
Preferably, the temperature of the precipitation reaction is 70-100 ℃; the precipitation reaction time is 2-5 h.
The invention provides the SiO in the technical scheme2@CaSiO3Hollow nanospheres or SiO prepared by the preparation method of the technical scheme2@CaSiO3The hollow nanospheres are applied to the field of drug-loading sustained release.
Preferably, the drug is loaded on the SiO2@CaSiO3The through hole of the hollow nanosphere and the hollow structure of the core layer.
The invention provides SiO2@CaSiO3The hollow nanospheres take hollow mesoporous silica nanospheres as core layers and calcium silicate as shell layers; the SiO2@CaSiO3The hollow nanospheres are distributed with a plurality of through holes which are communicated with the outside, and part of the through holes are communicated with the hollow structure of the core layer. In the invention, the silicon dioxide and the calcium silicate are inorganic salt carrier materials, the chemical composition of the inorganic salt carrier materials is similar to the mineral components of hard tissues such as human bones, teeth and the like, and the inorganic salt carrier materials have good biocompatibility, osteoconductivity and degradability; in vitro adsorption of drugs to SiO2@CaSiO3After the through holes and the hollow structures of the hollow nanospheres are filled with SiO loaded with the medicament in an injection mode2@CaSiO3The hollow nanospheres are implanted in vivo, and due to low drug concentration in body fluid, the drug gradually comes from SiO2@CaSiO3The hollow nanospheres are released from the interior to achieve the purpose of exerting the drug effect for a long time; the hollow structure of the nuclear layer can greatly improve SiO2@CaSiO3The hollow nanospheres have drug loading capacity, so that the drug slow release system has the advantages of good drug loading performance, drug slow release performance and the like, and can safely, slowly and efficiently control the drug to be released as required; under the condition of low pH, the shell layer CaSiO3The release rate and the release amount of the drug are improved after the drug is damaged, and the effect of pH response is achieved.
Drawings
FIG. 1 is a diagram of SiO of the present invention2@CaSiO3Reaction schematic diagram of hollow nanospheres;
FIG. 2 is a scanning electron microscope image of the hollow mesoporous silica nanospheres of the present invention;
FIG. 3 is SiO according to the present invention2@CaSiO3Scanning electron micrographs of hollow nanospheres;
FIG. 4 shows SiO in test example 12@CaSiO3A DOX concentration standard curve chart of hollow nanosphere load;
FIG. 5 shows SiO in test example 22@CaSiO3A release curve graph of hollow nanosphere loaded DOX accumulated in a PBS buffer solution;
FIG. 6 shows SiO prepared by the present invention2@CaSiO3Transmission electron microscopy images of hollow nanospheres.
Detailed Description
The invention provides SiO2@CaSiO3The hollow nanospheres take hollow mesoporous silica nanospheres as core layers and calcium silicate as shell layers; the SiO2@CaSiO3The hollow nanospheres are distributed with a plurality of through holes which are communicated with the outside, and part of the through holes are communicated with the hollow structure of the core layer.
In the invention, the particle size of the hollow mesoporous silica nanospheres is preferably 300-500 nm, and more preferably 300-400 nm; the diameter of the hollow structure of the hollow mesoporous silica nanosphere is preferably 200-300 nm, and more preferably 200 nm. In the invention, mesopores are distributed on the surface of the hollow mesoporous silica nanospheres, and the aperture is preferably 4-6 nm; part of the mesopores are communicated with the hollow structure of the hollow mesoporous silica nanospheres.
In the present invention, the calcium silicate is preferably SiO in mass2@CaSiO3The total mass of the hollow nanospheres is 5-10%, and more preferably 6-8%.
In the present invention, the SiO2@CaSiO3The particle size of the hollow nanospheres is preferably 300-500 nm, and more preferably 400-500 nm. In the present invention, the SiO2@CaSiO3The aperture of the through hole of the hollow nanosphere is preferably4-6 nm, more preferably 6 nm.
The invention also provides the SiO in the technical scheme2@CaSiO3The preparation method of the hollow nanosphere comprises the following steps:
dispersing hollow mesoporous silica nanospheres in water to obtain silica nanosphere dispersion liquid;
mixing the silicon dioxide nanosphere dispersion liquid with a surfactant to obtain a modified silicon dioxide nanosphere dispersion liquid;
mixing the modified silicon dioxide nanosphere dispersion liquid with an alkaline substance, adjusting the pH value of a system to be 12-13, adding a calcium source, and carrying out a precipitation reaction to obtain SiO2@CaSiO3Hollow nanospheres.
The invention disperses the hollow mesoporous silicon dioxide nanospheres in water to obtain the silicon dioxide nanosphere dispersion liquid. In the present invention, the structure of the hollow mesoporous silica nanospheres is consistent with that of the hollow mesoporous silica nanospheres as the core layer, which is not described herein again. In the invention, the dosage ratio of the hollow mesoporous silica nanospheres to water is preferably 1-2 g: 2-4L, more preferably 1.5 g: 2.5L.
The preparation method of the hollow mesoporous silica nanosphere has no special requirements, and the hollow mesoporous silica nanosphere can be prepared by a preparation method well known by the technical personnel in the field, and particularly preferably by an improved stober method. In the present invention, the preparation method of the hollow mesoporous silica nanosphere preferably comprises the following steps:
mixing ethanol, water, ammonia water and hexadecyl trimethyl ammonium bromide to obtain a mixed solution;
dropwise adding ethyl orthosilicate into the mixed solution, and carrying out water bath reaction to obtain mesoporous silica nanospheres;
and mixing the mesoporous silica nanospheres with water, and stirring and refluxing to obtain the hollow mesoporous silica nanospheres.
In the present invention, the mass concentration of the ammonia water is preferably 30%; the volume ratio of the ethanol to the water to the ammonia water is preferably 30:50: 1. In the present invention, the ratio of the amount of ethanol to the amount of cetyltrimethylammonium bromide is preferably 1 mL: 5 mg. According to the invention, ethanol, water and ammonia water are preferably uniformly mixed at room temperature, and then hexadecyl trimethyl ammonium bromide is added to be subjected to ultrasonic dispersion to obtain a mixed solution. In the present invention, the power of the ultrasonic dispersion is preferably 40hHz, and the time is preferably 30 min.
After the mixed solution is obtained, the invention preferably drops ethyl orthosilicate in the mixed solution to carry out water bath reaction to obtain the mesoporous silica nanosphere. In the present invention, the volume ratio of ethanol to ethyl orthosilicate is preferably 30: 1. In the present invention, the dropping rate of the tetraethoxysilane is preferably 1 mL/min. In the present invention, the temperature of the water bath reaction is preferably 35 ℃; the time of the water bath reaction is preferably 24 hours.
According to the invention, preferably, after the water bath reaction, the obtained solid product is washed and dried to obtain the mesoporous silica nanosphere. In the present invention, the washing method is preferably a method of centrifuging and washing with water and ethanol several times. The invention removes unreacted ammonia and hexadecyl trimethyl ammonium bromide by washing. In the invention, the drying temperature is preferably 60-90 ℃, and more preferably 70-80 ℃; the drying time is preferably 24 h.
After the mesoporous silica nanospheres are obtained, the mesoporous silica nanospheres are preferably mixed with water, and stirred and refluxed to obtain the hollow mesoporous silica nanospheres. In the invention, the mass ratio of the mesoporous silica nanospheres to water is preferably 1: 200; the water is preferably deionized water. In the present invention, the stirring speed of the stirring reflux is preferably 500 rpm; the temperature of the stirring reflux is preferably 70 ℃; the stirring reflux is preferably carried out under oil bath conditions; the stirring and refluxing time is preferably 18-20 h.
According to the invention, preferably, after the stirring and refluxing, the obtained product is sequentially washed and dried to obtain the hollow mesoporous silica nanospheres. In the present invention, the washing method preferably includes multiple centrifugal washing with water and ethanol. In the invention, the drying temperature is preferably 60-90 ℃, and more preferably 70-80 ℃; the drying time is preferably 12-24 h.
The invention prepares the mesoporous silica nanospheres with uniform particle size and average particle size of 300nm by an improved stober method, and the hollow mesoporous silica nanospheres are obtained after refluxing in water for a certain time.
After the hollow mesoporous silica nanospheres are dispersed in water to obtain silica nanosphere dispersion liquid, the silica nanosphere dispersion liquid is mixed with a surfactant to obtain modified silica nanosphere dispersion liquid. In the present invention, the surfactant preferably includes one or more of cetyltrimethylammonium bromide, polyvinylpyrrolidone, octadecyldimethylhydroxyethylammonium and dodecyldimethylbenzylammonium chloride, and more preferably cetyltrimethylammonium bromide. In the invention, the mass ratio of the surfactant to the hollow mesoporous silica nanospheres is preferably 2-7: 10-20, and more preferably 1.5-2.5: 10.
In the invention, the mixing of the silica nanosphere dispersion and the surfactant is preferably carried out under a stirring condition, and the stirring speed is preferably 300-500 rpm, and more preferably 400 rpm; the stirring time is preferably 10-40 min, and more preferably 30 min. In the present invention, the mixing is preferably performed at room temperature, and particularly preferably at 25 ℃. In the mixing process, the surfactant is combined with silicon hydroxyl on the surface of the silicon dioxide to obtain the modified silicon dioxide nanosphere.
After the modified silicon dioxide nanosphere dispersion liquid is obtained, the modified silicon dioxide nanosphere dispersion liquid and an alkaline substance are mixed, the pH value of a system is adjusted to be 12-13, a calcium source is added, and a precipitation reaction is carried out to obtain SiO2@CaSiO3Hollow nanospheres. In the present invention, the basic substance preferably includes sodium hydroxide, sodium acetate or ammonia water, more preferably sodium hydroxide; when the alkaline substance is ammonia water, the mass concentration of the ammonia water is preferably 30%. In the present invention, the amount of the alkaline substance added is preferably such that the pH of the system is 12 to 13. The invention adds alkaline substances to provide alkaline environment for the system and can oxidize modified dioxideEtching the surface of the silicon nanosphere to generate silicate ions.
In the present invention, the calcium source preferably comprises calcium nitrate, calcium chloride or calcium sulfate, more preferably calcium nitrate. In the invention, the mass ratio of the calcium source to the hollow mesoporous silica nanospheres is preferably 6-9: 5-10, and more preferably 5-8: 10.
In the invention, the temperature of the precipitation reaction is preferably 70-100 ℃, and more preferably 80-95 ℃; the time of the precipitation reaction is preferably 2-6 h, and more preferably 3-5 h. In the present invention, the precipitation reaction is carried out under stirring conditions, preferably at a rate of 400 rpm. In the precipitation reaction process, the calcium source reacts with silicate ions generated after the silicon dioxide is etched to generate calcium silicate, and the calcium silicate is deposited on the surface of the etched hollow mesoporous silicon dioxide nanospheres.
After the precipitation reaction, the obtained product is preferably washed and dried in sequence to obtain SiO2@CaSiO3Hollow nanospheres. In the present invention, the method of washing preferably comprises: washing with water and ethanol repeatedly, and centrifuging. The invention has no special requirement on the washing times, and the conventional washing method of the technicians in the field can be adopted. In the invention, the drying is preferably vacuum drying, and the drying temperature is preferably 60-90 ℃, and more preferably 70-80 ℃; the drying time is preferably 24 h.
The invention also provides the SiO in the technical scheme2@CaSiO3Hollow nanospheres or SiO prepared by the preparation method of the technical scheme2@CaSiO3The hollow nanospheres are applied to the field of drug-loading sustained release. In the present invention, the drug is preferably supported on SiO2@CaSiO3The through hole of the hollow nanosphere and the hollow structure of the core layer. In the present invention, the loaded drug preferably comprises doxorubicin (C)27H29NO11Doxorubicin, DOX) and/or curcumin.
In the present invention, the SiO2@CaSiO3The method for loading the hollow nanospheres with the medicament is preferably mixing, particularly preferablySelecting as follows: subjecting the SiO2@CaSiO3Mixing hollow nanosphere with dispersion or solution containing drug, stirring at room temperature to adsorb drug, centrifuging, and drying to obtain drug-loaded SiO2@CaSiO3Hollow nanospheres. In the invention, the stirring time is preferably 24-48 h.
In a particular embodiment of the invention, the SiO is present per gram2@CaSiO3The drug loading capacity of the hollow nanospheres is preferably 0.08-0.10 g; the SiO2@CaSiO3The encapsulation rate of the hollow nanospheres is preferably more than 80%, and more preferably 82-92%.
SiO2@CaSiO3The hollow nanosphere has the advantages of large specific surface area, good biocompatibility and the like due to the hollow structure and the through holes, and has the advantages of high drug loading rate, high entrapment rate, small side effect and the like when being used as a drug slow-release carrier. The invention adsorbs the medicine to SiO in vitro2@CaSiO3After the hollow nanospheres are arranged in the through holes and the hollow structures, the SiO loaded with the medicine is injected2@CaSiO3The hollow nanospheres are implanted in vivo, and due to low drug concentration in body fluid, the drug gradually comes from SiO2@CaSiO3The hollow nanospheres are released from the interior to achieve the purpose of exerting the drug effect for a long time; the hollow structure of the nuclear layer can greatly improve SiO2@CaSiO3The hollow nanospheres have drug loading capacity, so that the drug sustained-release system has the advantages of good drug loading performance, drug sustained-release performance and the like, and can safely, slowly and efficiently control the drug to be released as required. The invention controls SiO2@CaSiO3The shape and the particle size of the hollow nanosphere can effectively control the drug release percentage and the slow release rate and prolong the drug treatment time, in the invention, SiO2@CaSiO3The more regular the spherical structure of the hollow nanosphere is, the more favorable the medicament transportation can be realized because the hollow nanosphere is in a uniform state when being taken as a carrier or injected into a human body.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the 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.
Example 1
Uniformly mixing 30mL of ethanol and 50mL of water, dispersing 150mg of hexadecyl trimethyl ammonium bromide in a mixed solvent, adding 1mL of ammonia water with the mass concentration of 30%, dropwise adding 1mL of tetraethoxysilane under rapid stirring, carrying out water bath reaction on the obtained mixed solution at the temperature of 35 ℃ for 24 hours, washing the obtained mesoporous silica microspheres with water and ethanol after the reaction is finished, centrifuging, transferring the obtained mesoporous silica microspheres into a vacuum drying oven, and drying at the temperature of 70 ℃ for 24 hours to obtain mesoporous silica nanospheres;
dispersing 2g of the mesoporous silica nanospheres in 400mL of water, stirring and refluxing for 20h at 70 ℃, repeatedly washing with water and ethanol after the reaction is finished, centrifuging, and transferring to a vacuum drying oven to dry for 24h at 70 ℃ to obtain the hollow mesoporous silica nanospheres.
Preparation of SiO by the method shown in FIG. 12@CaSiO3Hollow nanospheres: dispersing 100mg of the hollow mesoporous silica nanospheres in 150mL of water to obtain silica nanosphere dispersion liquid;
adding 25mg of hexadecyl trimethyl ammonium bromide into the silicon dioxide nanosphere dispersion liquid under stirring, and stirring at the constant speed of 25 ℃ for 30min to obtain a modified silicon dioxide nanosphere dispersion liquid;
adding sodium hydroxide into the modified silicon dioxide nanosphere dispersion liquid for etching, adjusting the pH value to 12, then adding 80mg of calcium nitrate, reacting for 3 hours at the temperature of 95 ℃ under uniform stirring, repeatedly washing a solid product obtained after the reaction with water and ethanol, centrifuging, transferring into a vacuum drying oven, and drying for 24 hours at the temperature of 70 ℃ to obtain SiO2@CaSiO3Hollow nanospheres.
FIG. 2 is a scanning electron microscope image of the hollow mesoporous silica nanospheres of the present invention. As can be seen from FIG. 2, the hollow mesoporous silica nanospheres prepared by the method have uniform particle size, and the average particle size is 500 nm.
FIG. 3 is SiO according to the present invention2@CaSiO3Scanning electron microscopy images of hollow nanospheres. As can be seen from FIG. 3, SiO prepared by the present invention2@CaSiO3The hollow nanospheres have hollow structures inside and porous surfaces.
FIG. 6 shows SiO of the present invention2@CaSiO3Transmission electron microscopy images of hollow nanospheres. As can be seen from FIG. 6, SiO2@CaSiO3The hollow nanospheres are in a hollow double-shell structure, and are SiO in darker colors2The outermost layer is shallower CaSiO3。
SiO prepared in this example2@CaSiO3The average particle diameter of the hollow nanospheres is 500nm, and the SiO is2@CaSiO3A plurality of through holes are distributed on the hollow nanospheres, and the aperture of each through hole is 6 nm.
Example 2
Preparing hollow mesoporous silica nanospheres according to the method of example 1;
dispersing 100mg of the hollow mesoporous silica nanospheres in 150mL of water to obtain silica nanosphere dispersion liquid;
adding 15mg of hexadecyl trimethyl ammonium bromide into the silicon dioxide nanosphere dispersion liquid under stirring, and stirring at the constant speed of 25 ℃ for 30min to obtain a modified silicon dioxide nanosphere dispersion liquid;
adding sodium hydroxide into the modified silicon dioxide nanosphere dispersion liquid for etching, adjusting the pH value to 12, then adding 50mg of calcium nitrate, reacting for 6 hours at 80 ℃ under the condition of uniform stirring, repeatedly washing a solid product obtained after the reaction with water and ethanol, centrifuging, transferring into a vacuum drying oven, and drying for 24 hours at 70 ℃ to obtain SiO2@CaSiO3Hollow nanospheres.
SiO prepared in this example2@CaSiO3The average particle diameter of the hollow nanospheres is 400nm, and the SiO is2@CaSiO3A plurality of through holes are distributed on the hollow nanospheres, and the aperture of each through hole is 4 nm.
Example 3
Preparing hollow mesoporous silica nanospheres according to the method in the embodiment 1;
dispersing 100mg of the hollow mesoporous silica nanospheres in 150mL of water to obtain silica nanosphere dispersion liquid;
adding 25mg of hexadecyl trimethyl ammonium bromide into the silicon dioxide nanosphere dispersion liquid under stirring, and stirring at the constant speed of 25 ℃ for 30min to obtain a modified silicon dioxide nanosphere dispersion liquid;
adding sodium acetate into the modified silicon dioxide nanosphere dispersion liquid for etching, adjusting the pH value to 12, then adding 80mg of calcium nitrate, reacting for 3 hours under the condition of uniformly stirring at 95 ℃, repeatedly washing a solid product obtained after the reaction by using water and ethanol, centrifuging, transferring into a vacuum drying oven, and drying for 24 hours at 70 ℃ to obtain SiO2@CaSiO3Hollow nanospheres.
SiO prepared in this example2@CaSiO3The average particle diameter of the hollow nanospheres is 500nm, and the SiO is2@CaSiO3A plurality of through holes are distributed on the hollow nanospheres, and the aperture of each through hole is 4 nm.
Test example 1
For the SiO prepared in examples 1 to 3, respectively2@CaSiO3The hollow nanospheres were tested for DOX encapsulation efficiency and drug loading:
the SiO prepared in examples 1 to 3 were weighed separately2@CaSiO3Respectively putting 50mg of hollow nanospheres into 3 DOX solutions with the concentration of 5mL and 1mg/mL respectively, and uniformly mixing for 48 hours in a dark place to obtain DOX-loaded SiO2@CaSiO3A hollow nanosphere; separating with ultracentrifuge, collecting supernatant, washing with deionized water for three times (1 mL each time), centrifuging, and collecting supernatant. Measuring an OD480 value of the supernatant by using an ultraviolet spectrophotometer, wherein the OD480 value refers to setting an ultraviolet absorption wavelength to be 480nm, and performing an ultraviolet absorbance test on the supernatant to obtain a test result; SiO was calculated from the DOX concentration standard curve as shown in FIG. 42@CaSiO3The drug loading and encapsulation efficiency of the hollow nanospheres are calculated according to the following formula, and the obtained results are shown in table 1:
in formula I and formula II, the initial DOX mass is 5mg, and the supernatant DOX mass refers to the mass of DOX in the supernatant.
TABLE 1 SiO prepared in examples 1 to 32@CaSiO3DOX encapsulation rate and drug loading rate detection result of hollow nanospheres
| Sample number | Drug loading | Encapsulation efficiency (%) |
| Example 1 | 0.0916 | 91.623 |
| Example 2 | 0.0826 | 82.565 |
| Example 3 | 0.0855 | 85.474 |
As can be seen from Table 1, per gram of the SiO2@CaSiO3The drug loading capacity of the hollow nanospheres is 0.08-0.10 g; the SiO2@CaSiO3Of hollow nanospheresThe encapsulation efficiency is more than 80 percent. The SiO provided by the invention2@CaSiO3The hollow nanosphere has high encapsulation efficiency, high drug loading rate, no toxicity, no harm and good biocompatibility.
Test example 2
For SiO prepared in example 32@CaSiO3The hollow nanospheres are subjected to in vitro drug release capability investigation at different pH values by the following method:
50mg of SiO prepared in example 3 are introduced2@CaSiO3Placing the hollow nanospheres in 5mL of DOX solution with the concentration of 1mg/mL, keeping out of the sun, and uniformly mixing for 48h to obtain DOX-loaded SiO2@CaSiO3A hollow nanosphere; two portions of 10mg of the DOX-loaded SiO2@CaSiO3The hollow nanospheres are respectively placed into 2 dialysis bags with molecular weight cut-off of 8000-10000, then respectively placed into 30mL PBS (phosphate buffer solution) with pH adjusted to 7.4 and 4.5 by using 0.5% HCl, and placed into water bath at 37 ℃ for carrying out in-vitro drug slow release experiments by magnetic stirring. 1mL of the sustained release solution was taken out at release times of 1, 2, 4, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120h, respectively, and then 1mL of PBS solution of the same pH was supplemented, and OD480 values of the sustained release solution at each time point were measured using an ultraviolet spectrophotometer, as shown in FIG. 5.
As can be seen from FIG. 5, the burst release of the drug occurs under different pH conditions before 20 hours, and the drug release is carried out slowly in the subsequent time, so that the effect of long-term and effective drug release is achieved. Under the environment of pH 4.5, the surface CaSiO3The shell layer is damaged to a certain extent, so that the drug release rate and the accumulated drug release amount are increased along with the reduction of the pH value, and the material is proved to have a certain pH response effect.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and amendments can be made without departing from the principle of the present invention, and these modifications and amendments should also be considered as the protection scope of the present invention.
Claims (8)
1. SiO (silicon dioxide)2@CaSiO3Hollow nanospheres, which take hollow mesoporous silica nanospheres as core layers and calcium silicate as core layersA shell layer; the SiO2@CaSiO3The hollow nanospheres are distributed with a plurality of through holes which are communicated with the outside, and part of the through holes are communicated with the hollow structure of the core layer.
2. SiO as claimed in claim 12@CaSiO3Hollow nanospheres characterized in that said SiO2@CaSiO3The particle size of the hollow nanospheres is 300-500 nm.
3. SiO according to claim 1 or 22@CaSiO3The hollow nanospheres are characterized in that the diameter of the hollow structure of the core layer is 200-300 nm; the aperture of the through hole is 4-6 nm.
4. SiO as claimed in claim 12@CaSiO3Hollow nanospheres characterized in that the calcium silicate comprises SiO by mass2@CaSiO35-10% of the total mass of the hollow nanospheres.
5. SiO as claimed in any one of claims 1 to 42@CaSiO3The preparation method of the hollow nanosphere comprises the following steps:
dispersing hollow mesoporous silica nanospheres in water to obtain silica nanosphere dispersion liquid;
mixing the silicon dioxide nanosphere dispersion liquid with a surfactant to obtain a modified silicon dioxide nanosphere dispersion liquid;
mixing the modified silicon dioxide nanosphere dispersion liquid with an alkaline substance, adjusting the pH value of a system to be 12-13, adding a calcium source, and carrying out a precipitation reaction to obtain SiO2@CaSiO3Hollow nanospheres;
the mass ratio of the calcium source to the hollow mesoporous silica nanospheres is 6-9: 5-10; the temperature of the precipitation reaction is 70-100 ℃; the precipitation reaction time is 2-5 h.
6. The preparation method of claim 5, wherein the mass ratio of the surfactant to the hollow mesoporous silica nanospheres is 2-7: 10-20.
7. SiO as claimed in any one of claims 1 to 42@CaSiO3Hollow nanospheres or SiO obtained by the preparation method of any one of claims 5 to 62@CaSiO3The hollow nanospheres are applied to the field of drug-loading sustained release.
8. The use of claim 7, wherein the drug is loaded on the SiO2@CaSiO3The through hole of the hollow nanosphere and the hollow structure of the core layer.
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