CN110448698B - Drug controlled release mesoporous silicon nanoparticle and preparation method thereof - Google Patents
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Abstract
The invention discloses a drug controlled release mesoporous silicon nanoparticle and a preparation method thereof, wherein the preparation method comprises the following steps: (1) Adding 3-aminopropyltriethoxysilane into mesoporous silicon nanoparticles, taking methylbenzene as a solvent, performing reflux reaction under the protection of nitrogen, washing with ultrapure water and ethanol after the reaction is finished, and performing vacuum drying to obtain aminated mesoporous silicon nanoparticles MSN-NH 2 (ii) a (2) Dissolving aminated mesoporous silicon nanoparticles in acetonitrile, adding 1-pyrene formaldehyde for reaction, centrifuging after the reaction is finished, washing with ultrapure water and ethanol, and drying in vacuum to obtain MSN-N = CH-Py; (3) And adding a drug solution to be loaded into the MSN-N = CH-Py to react, adding beta-cyclodextrin to continue reacting after the reaction is finished, centrifuging after the reaction is finished, washing with ultrapure water and ethanol, and drying in vacuum to obtain the pharmaceutical composition. The drug controlled release mesoporous silicon nanoparticle has good responsiveness to pH, and has good drug loading capacity and drug controlled release performance.
Description
Technical Field
The invention relates to the technical field of drug controlled release, in particular to drug controlled release mesoporous silicon nanoparticles and a preparation method thereof.
Background
Edaravone (ED) is an effective free radical scavenger and is now widely used clinically for the treatment of ischemic stroke. ED has also been reported to have a protective effect in IRI (Ischemic Reperfusion Injury) of organs such as lung, kidney, heart, liver, and the like. ROS (reactive oxygen species) damage can cause cellular edema and apoptosis, and a number of studies have shown that ED can reduce apoptosis by scavenging ROS in vivo. ShimodaM et al found that edaravone can reduce HIRI (hepatic ischemia reperfusion injury) by inhibiting apoptosis.
Mesoporous Silicon Nanoparticles (MSNs) have been widely used in the field of drug release in recent years due to their characteristics of large specific surface area, easy surface modification, and good biocompatibility. Compared with carbon nanoparticles and the like, the mesoporous silicon nanoparticles can be naturally degraded in organisms without toxicity. The particle size of the MSNs can be adjusted within the range of 50-1000 nm, and the MSNs have good biocompatibility and are easy to be taken by cells. By modifying a structure having a specific biological function on its surface, a specific cell targeting effect can be obtained. The surface of the mesoporous silica has abundant silicon hydroxyl, so that various functional groups can be easily modified on the surface of the mesoporous silica, and the mesoporous silica can realize the functions of targeted drug delivery, cell imaging and the like after being combined with fluorescent substances, polypeptides and the like. The modified MSNs can respond to specific stimulation, such as pH, enzymes and the like, release of the encapsulated drugs can be carried out at a target position but cannot respond in the transportation process and normal positions, so that good targeted therapy can be realized, the release of the encapsulated drugs at other positions is reduced, and the potential side effects of the drugs are obviously reduced. Therefore, MSNs have been the focus of research in many disciplines such as medicine and materials science.
The design mechanism of the pH-responsive controlled drug release system is based on the difference of pH values of tissues or areas of inflammation, tumor and the like at different parts in vivo. In the HIRI process, tissues are subjected to ischemia and hypoxia, intracellular acidosis and glycolysis are enhanced to generate a large amount of lactic acid, and a local micro environment is acidic, so that the HIRI process becomes a good response condition of a controlled release system of the medicine. The existing drug controlled release system also has the problems of poor pH responsiveness, drug loading capacity and drug controlled release performance.
Disclosure of Invention
The invention mainly aims to provide a drug controlled release mesoporous silicon nanoparticle and a preparation method thereof, and at least solves the problems of poor pH responsiveness and poor drug controlled release performance of a drug controlled release system in the prior art.
In order to achieve the above objects, according to one aspect of the present invention, there is provided a method for preparing mesoporous silicon nanoparticles for controlled drug release, the method comprising the steps of:
(1) Adding 3-aminopropyl triethoxy into mesoporous silicon nano particlesSilane is taken as a solvent, reflux reaction is carried out under the protection of nitrogen, ultrapure water and ethanol are used for washing after the reaction is finished, and vacuum drying is carried out to obtain aminated mesoporous silicon nano-particles MSN-NH 2 ；
(2) Dissolving the aminated mesoporous silicon nanoparticles obtained in the step (1) in acetonitrile, adding 1-pyrene formaldehyde for reaction, reacting aldehyde groups in the 1-pyrene formaldehyde with amino groups on the aminated mesoporous silicon nanoparticles to form carbon-nitrogen double bonds, centrifuging after the reaction is finished, washing with ultrapure water and ethanol, and drying in vacuum to obtain MSN-N = CH-Py;
(3) And (3) adding the MSN-N = CH-Py obtained in the step (2) into a drug solution to be loaded for reaction, adding beta-cyclodextrin for continuous reaction after the reaction is finished, centrifuging after the reaction is finished, washing with ultrapure water and ethanol, and drying in vacuum to obtain the drug-loaded controlled-release mesoporous silicon nanoparticles.
The method takes Mesoporous Silicon Nanoparticles (MSNs) as a drug carrier material, and modifies amino groups on the surfaces of the mesoporous silicon nanoparticles by using 3-Aminopropyltriethoxysilane (APTES) to obtain aminated mesoporous silicon nanoparticles; then, forming a carbon-nitrogen double bond by the interaction of aldehyde group (pyrene formaldehyde, py-CHO) and amino; after loading a drug (such as edaravone), beta-cyclodextrin is used for blocking to form the drug controlled release mesoporous silicon nanoparticles.
According to the invention, a pH responsive drug sustained-release system is adopted, carbon-nitrogen double bonds can be broken in an acidic environment of a tumor tissue region, amino groups are exposed, the effect of assisting carrier transmembrane is achieved, and meanwhile, cyclodextrin is taken as a gating group to leave, so that the drug is released. When the system is in a tumor microenvironment, part of the drug begins to be slowly released outside the cancer cells when meeting an acidic environment, but the mesoporous silicon is actively phagocytized by the cells, and compared with the acidity of the tumor microenvironment, the acidity of lysosomes in the cells is lower, so that more drugs can be controllably released after the system enters the cells; the medicine released outside the cancer cells can still enter the nearby cancer cells to achieve the treatment effect.
Further, in the step (1), the mesoporous silicon nanoparticles are prepared by the following method: dissolving hexadecyl trimethyl ammonium bromide in deionized water, adding a sodium hydroxide solution, regulating the temperature to 65-75 ℃, keeping the temperature for 25-35min, quickly dropwise adding tetraethoxysilane under vigorous stirring, adding ethyl acetate after 1-2min, continuously stirring for 1.5-2.5h, centrifuging after the reaction is finished, washing with ultrapure water and ethanol, and performing vacuum drying at 55-65 ℃ overnight to obtain the mesoporous silicon nanoparticles.
Further, after performing vacuum drying in step (1), the method further comprises the following steps: adding ethanol and concentrated hydrochloric acid with the mass fraction of 37% into the dried product, reacting for 20-28h at 65-75 ℃, centrifuging after the reaction is finished, washing with ultrapure water and methanol, and drying in vacuum overnight at 55-65 ℃ to obtain the aminated mesoporous silicon nanoparticles.
Further, in the step (1), the reflux reaction time is 20-28h, the reaction product is washed by ultrapure water and ethanol for at least three times after the reflux reaction is finished, and the temperature of vacuum drying is 65-75 ℃.
Further, in the step (1), the charging mass-volume ratio of the mesoporous silicon nanoparticles to the 3-aminopropyltriethoxysilane is 2:1 mg/. Mu.L.
Further, in the step (2), 1-pyrene formaldehyde is added for reaction for 2.5-3.5h, and after the reaction is finished, the mixture is centrifuged, washed with ultrapure water and ethanol for at least three times, and then dried in vacuum at 65-75 ℃.
Further, in the step (2), the feeding mass ratio of the aminated mesoporous silicon nanoparticles to 1-pyrene formaldehyde is 10:1.
further, in the step (3), the reaction time of adding the drug solution to be loaded for reaction is 2.5-3.5h, and the reaction time of adding the beta-cyclodextrin for reaction is 20-28h.
Further, in the step (3), the concentration of the drug solution to be loaded is 1-2mg/mL, and the concentration of the beta-cyclodextrin is 1.5-2.5mmol/L.
According to another aspect of the present invention, there is provided a controlled release mesoporous silicon nanoparticle, which is prepared by the above preparation method of the controlled release mesoporous silicon nanoparticle.
Further, the drug loaded was edaravone.
Compared with the prior art, the invention has the following beneficial effects:
the invention takes mesoporous silicon nanoparticles as a drug carrier material, amino groups are modified on the surfaces of the mesoporous silicon nanoparticles by using 3-aminopropyltriethoxysilane to obtain aminated mesoporous silicon nanoparticles, aldehyde groups (pyrene formaldehyde) and amino groups are interacted to form carbon-nitrogen double bonds, the carbon-nitrogen double bonds can be broken in an acidic environment of a tumor tissue area, and beta-cyclodextrin is used for plugging after loading drugs (such as edaravone), so that the drug controlled release mesoporous silicon nanoparticles with pH responsiveness are formed. The obtained drug controlled release mesoporous silicon nanoparticles have good responsiveness to pH, the release rate in normal tissues is extremely low, but in acid micro environments such as ischemia reperfusion and tumors, beta-cyclodextrin falls off from the surface of the mesoporous silicon due to carbon-carbon double bond fracture, so that a large amount of drugs are released from the pore channels. Therefore, under the condition of the same dosage, better action effect can be achieved. The drug controlled release mesoporous silicon nanoparticle has good drug loading capacity and drug controlled release performance.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate embodiments of the invention and, together with the description, serve to explain the invention and not to limit the invention. In the drawings:
fig. 1 is a schematic view illustrating preparation and release of a controlled release mesoporous silicon nanoparticle prepared in example 1 of the present invention.
Fig. 2 is a transmission electron microscope image of the mesoporous silicon nanoparticles prepared in example 1 of the present invention.
Fig. 3 is an infrared spectrum of the mesoporous silicon nanoparticle prepared in example 1 of the present invention.
FIG. 4 is a graph of the in vitro release of two-photon dyes at different pH values.
FIG. 5 is a graph showing the UV absorption of edaravone at various concentrations.
FIG. 6 is an edaravone concentration-UV absorbance calibration curve.
Detailed Description
In order to facilitate an understanding of the invention, the invention will now be described more fully and in detail with reference to the preferred embodiments, but the scope of the invention is not limited to the specific embodiments described below.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention.
Unless otherwise specifically indicated, various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or can be prepared by existing methods.
Example 1
The preparation method of the drug controlled release mesoporous silicon nanoparticles comprises the following steps:
(1) Synthesis of mesoporous silicon nanoparticles
Weighing 0.50g of hexadecyl trimethyl ammonium bromide (CTAB), dissolving in 240mL of deionized water, adding 1.75mL of 2.0M NaOH solution, adjusting the temperature to 70 ℃, keeping the temperature for 30min, then quickly dropwise adding 2.75mL of Tetraethoxysilane (TEOS) under vigorous stirring, adding 2.50mL of ethyl acetate after 1min, continuously stirring for 2h until white precipitate appears, centrifuging, washing with ultrapure water and ethanol (three times), and vacuum-drying at 60 ℃ overnight to obtain white mesoporous solid silicon nanoparticles;
(2) Mesoporous silicon nanoparticle amination modification
Weighing 100mg of the prepared mesoporous silicon nanoparticles, adding 50 mu L of 3-Aminopropyltriethoxysilane (APTES), refluxing in 10mL of dry toluene under the protection of nitrogen for 24h, centrifuging to remove toluene, washing with ultrapure water and ethanol (three times), and vacuum drying at 70 ℃;
(3) Removal of hexadecyltrimethylammonium bromide
Weighing 1g of the prepared product, adding 100mL of ethanol and 1mL of concentrated hydrochloric acid with the mass fraction of 37%, reacting at 70 ℃ for 24h to remove the surfactant cetyl trimethyl ammonium bromide in the mesoporous silicon pore channel, centrifuging, washing with ultrapure water and methanol vigorously, and vacuum drying at 60 ℃ overnight to obtain the aminated mesoporous silica without the surfactantSilicon nanoparticles (MSN-NH) 2 )；
(4) Pyrenecarboxaldehyde reacts with amino groups to form carbon-nitrogen double bonds
100mg of MSN-NH 2 Dissolving in 30mL acetonitrile, adding 1-pyrene formaldehyde (Py-CHO) 10mg, reacting for 3h, centrifuging, washing with ultrapure water and ethanol (three times), and vacuum drying at 70 ℃ to obtain MSN-N = CH-Py;
(5) Edaravone loaded with medicine
Weighing the obtained MSN-N = CH-Py 10mg, adding 5mL of 1.5mg/mL edaravone injection, reacting for 3h, adding 1mL of 2mM beta-cyclodextrin (beta-CD), reacting for 24h, centrifuging, washing with ultrapure water and ethanol for several times, collecting washing liquid, and vacuum drying overnight to obtain the pH responsive drug controlled release mesoporous silicon nanoparticle (ED @ MSN) loaded with edaravone.
Fig. 1 is a schematic view illustrating preparation and release of the mesoporous silicon nanoparticles for controlled drug release according to the present embodiment; FIG. 2 is a transmission electron microscope image of mesoporous silicon nanoparticles prepared in the present example; fig. 3 is an infrared spectrum of the aminated mesoporous silicon nanoparticle prepared in this example.
Determining the edaravone entrapment amount:
the edaravone has an absorption peak at 280nm as determined by ultraviolet spectroscopy. Preparing edaravone solutions with different concentrations, measuring the ultraviolet absorbance values of the edaravone solutions, and drawing an edaravone concentration-ultraviolet absorbance standard curve. The concentration of the washing liquid can be calculated by measuring the ultraviolet absorption value of the washing liquid, and the encapsulation amount of the edaravone can be further obtained. FIG. 5 is a graph of ultraviolet absorption of edaravone in different concentrations, and FIG. 6 is a calibration curve of edaravone concentration versus ultraviolet absorbance.
The in vitro application behavior of the mesoporous silicon nanoparticles for controlled drug release of the present example was examined:
loading of simulated drug-two-photon dye:
weighing the obtained MSN-N = CH-Py 14.7mg, dissolving in 4mL deionized water, adding 20 muM two-photon dye (TP) 10 muL, reacting for 3h, adding 2mM beta-cyclodextrin (beta-CD) 1mL, reacting for 24h, centrifuging, washing with ultrapure water and ethanol for several times, and vacuum drying overnight to obtain the pH-responsive mesoporous silicon nanoparticle (TP @ MSN) loaded with the two-photon dye (TP).
Detecting the release rate of the two-photon dye under different pH environments:
preparing Tris-HCl buffer solutions with pH values of 3, 4, 5, 6, 7, 8 and 9 respectively. Two-photon dye (TP) release was measured by fluorescence spectroscopy with an excitation of 370 μm and a maximum wavelength at 460 nm. And preparing TP solutions with different concentrations, detecting the fluorescence values of the TP solutions, and making a concentration-fluorescence value standard curve. The prepared Tris-HCl buffer solutions with the pH values of 3, 4, 5, 6, 7, 8 and 9 are used as release solutions. Equal amounts of TP @ MSN were dissolved in 1mL of the buffer solution prepared above, and the solution was placed in dialysis bags, which were placed in respective test tubes containing 4mL of the release solution, and the concentration of TP dye in the release solution was measured by taking samples at intervals. The release experiment was performed 3 times in parallel, and the release of the two-photon dye was calculated. FIG. 4 is a graph of the in vitro release of two-photon dyes at different pH values. As can be seen from fig. 4, the two-photon dye release rate was high when the buffer was acidic (pH 3, 4, 5, 6), and was relatively low when the buffer was basic or neutral (pH 7, 8, 9). The mesoporous silicon nano-particles for controlled drug release have good pH responsiveness and good controlled drug release performance.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. The preparation method of the drug controlled release mesoporous silicon nanoparticles is characterized by comprising the following steps:
(1) Adding 3-aminopropyltriethoxysilane into mesoporous silicon nanoparticles, taking methylbenzene as a solvent, carrying out reflux reaction under the protection of nitrogen, washing with ultrapure water and ethanol after the reaction is finished, and carrying out vacuum drying to obtain aminated mesoporous silicon nanoparticles MSN-NH 2 ；
(2) Dissolving the aminated mesoporous silicon nanoparticles obtained in the step (1) in acetonitrile, adding 1-pyrene formaldehyde for reaction, so that aldehyde groups in the 1-pyrene formaldehyde and amino groups on the aminated mesoporous silicon nanoparticles react to form carbon-nitrogen double bonds, centrifuging after the reaction is finished, washing with ultrapure water and ethanol, and drying in vacuum to obtain MSN-N = CH-Py;
(3) Adding the MSN-N = CH-Py obtained in the step (2) into a drug solution to be loaded for reaction, adding beta-cyclodextrin for continuous reaction after the reaction is finished, centrifuging after the reaction is finished, washing with ultrapure water and ethanol, and drying in vacuum to obtain drug-loaded drug controlled-release mesoporous silicon nanoparticles;
in the step (1), the mesoporous silicon nanoparticles are prepared by the following method:
dissolving hexadecyl trimethyl ammonium bromide in deionized water, adding a sodium hydroxide solution, regulating the temperature to 65-75 ℃, keeping the temperature for 25-35min, quickly dropwise adding tetraethoxysilane under vigorous stirring, adding ethyl acetate after 1-2min, continuously stirring for 1.5-2.5h, centrifuging after the reaction is finished, washing with ultrapure water and ethanol, and performing vacuum drying at 55-65 ℃ overnight to obtain mesoporous silicon nanoparticles;
in the step (1), the feeding mass-volume ratio of the mesoporous silicon nanoparticles to the 3-aminopropyltriethoxysilane is 2:1 mg/. Mu.L;
in the step (3), the reaction time of adding the drug solution to be loaded for reaction is 2.5-3.5h, and the reaction time of adding the beta-cyclodextrin for continuous reaction is 20-28h; the concentration of the drug solution to be loaded is 1-2mg/mL, and the concentration of the beta-cyclodextrin is 1.5-2.5mmol/L.
2. The method for preparing the mesoporous silicon nanoparticles for controlled drug release according to claim 1, wherein in the step (1), after the steps of washing with ultrapure water and ethanol after the reaction is finished and vacuum drying, the method further comprises the following steps:
adding ethanol and concentrated hydrochloric acid with the mass fraction of 37% into the dried product, reacting for 20-28h at 65-75 ℃, centrifuging after the reaction is finished, washing with ultrapure water and methanol, and vacuum-drying overnight at 55-65 ℃ to obtain the aminated mesoporous silicon nanoparticles.
3. The method for preparing the mesoporous silicon nanoparticles for controlled drug release according to claim 1, wherein in the step (1), the time of the reflux reaction is 20-28h, the mesoporous silicon nanoparticles are washed with ultrapure water and ethanol at least three times after the reflux reaction is finished, and the temperature of the vacuum drying is 65-75 ℃.
4. The method for preparing the controlled-release mesoporous silicon nanoparticles for drugs according to claim 1, wherein in the step (2), the 1-pyrene formaldehyde is added for reaction for 2.5-3.5 hours, and after the reaction is finished, the reaction product is centrifuged, washed with ultrapure water and ethanol for at least three times, and then dried under vacuum at 65-75 ℃.
5. The method for preparing the controlled-release mesoporous silicon nanoparticles for drugs according to claim 1, wherein in the step (2), the feeding mass ratio of the aminated mesoporous silicon nanoparticles to the 1-pyrene formaldehyde is 10:1.
6. a controlled release mesoporous silicon nanoparticle, wherein the controlled release mesoporous silicon nanoparticle is prepared by the method for preparing the controlled release mesoporous silicon nanoparticle according to any one of claims 1 to 5.
7. The controlled-release mesoporous silicon nanoparticle according to claim 6, wherein the loaded drug is edaravone.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104922674A (en) * | 2015-04-10 | 2015-09-23 | 南京理工大学 | PH-stimulation response type intelligent nanometer container and preparation method thereof |
| CN107412194A (en) * | 2017-04-19 | 2017-12-01 | 武汉理工大学 | With stimuli responsive and divide storehouse intelligently nanometer particle of load medicine drug release feature and preparation method thereof |
| CN107456580A (en) * | 2017-07-21 | 2017-12-12 | 南京理工大学 | Acid and lipase Dual Sensitive nano container and preparation method thereof |
| CN109589418A (en) * | 2018-12-14 | 2019-04-09 | 华南理工大学 | A kind of mesoporous silicon oxide medicine-carried nano particles and its preparation method and application of the schiff bases copolymer cladding with pH responsiveness |
-
2019
- 2019-09-04 CN CN201910833062.3A patent/CN110448698B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104922674A (en) * | 2015-04-10 | 2015-09-23 | 南京理工大学 | PH-stimulation response type intelligent nanometer container and preparation method thereof |
| CN107412194A (en) * | 2017-04-19 | 2017-12-01 | 武汉理工大学 | With stimuli responsive and divide storehouse intelligently nanometer particle of load medicine drug release feature and preparation method thereof |
| CN107456580A (en) * | 2017-07-21 | 2017-12-12 | 南京理工大学 | Acid and lipase Dual Sensitive nano container and preparation method thereof |
| CN109589418A (en) * | 2018-12-14 | 2019-04-09 | 华南理工大学 | A kind of mesoporous silicon oxide medicine-carried nano particles and its preparation method and application of the schiff bases copolymer cladding with pH responsiveness |
Non-Patent Citations (2)
| Title |
|---|
| Autonomous in vitro anticancer drug release from mesoporous silica nanoparticles by pH-sensitive nanovalves;Huan Meng et al.;《J Am Chem Soc.》;20100915;第132卷(第36期);12690-12697 * |
| 荧光光谱法研究芘与β环糊精、羟丙基β-环糊精的相互作用;任峰 等;《厦门大学学报(自然科学版)》;20040531;第43卷(第3期);372-375 * |
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