CN113181375A - Nano medicine and its preparing method - Google Patents
Nano medicine and its preparing method Download PDFInfo
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- CN113181375A CN113181375A CN202110523487.1A CN202110523487A CN113181375A CN 113181375 A CN113181375 A CN 113181375A CN 202110523487 A CN202110523487 A CN 202110523487A CN 113181375 A CN113181375 A CN 113181375A
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- hydrotalcite
- atorvastatin
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nanotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of nano-drugs, in particular to a nano-drug and a preparation method thereof. The nano-drug comprises a targeted hydrotalcite nano-material and an active ingredient loaded on the targeted hydrotalcite nano-material, wherein the targeted hydrotalcite nano-material comprises a human ferritin heavy chain. The nano-drug takes the hydrotalcite nano-sheets as a carrier for loading the drug, and combines the effect of the ferritin heavy chain targeting the blood brain barrier so as to carry the drug to cross the blood brain barrier, thereby achieving the treatment effect on the ischemic stroke. Meanwhile, the application also provides a preparation method of the nano-drug for treating the ischemic stroke, the preparation method is simple, the equipment requirement is low, the curative effect is better through the verification of animal in vivo experiments, and the treatment cost of the ischemic stroke can be effectively reduced.
Description
Technical Field
The invention relates to the technical field of nano-drugs, in particular to a nano-drug and a preparation method thereof.
Background
The cerebral apoplexy is a disease which causes brain tissue damage because blood can not flow into the brain due to cerebral vessel rupture or blockage, and has become a main disease death factor in China in recent years, the number of patients who die due to the cerebral apoplexy in China accounts for one third of the number of dead patients who die due to the cerebral apoplexy in the world, the patients mainly comprise ischemic stroke and hemorrhagic stroke, the ischemic stroke is common in clinic, and the morbidity accounts for more than 80% of the cerebral stroke. Currently, the best clinical treatment method for ischemic stroke is thrombolytic therapy, i.e. antithrombotic drugs are intravenously injected within an optimal treatment time window of 4.5 hours after onset of disease to dissolve thrombus, thereby restoring cerebral blood perfusion. However, since the optimal treatment time window is known, most patients cannot receive effective treatment in a timely manner; in addition, thrombolytic therapy also carries the risk of inducing reperfusion injury and bleeding. Many preclinical studies show that neuroprotective agents (such as antioxidants, apoptosis inhibitors, etc.) have a good effect in treating ischemic stroke, but the presence of Blood Brain Barrier (BBB) prevents most of the central nervous system drugs from entering the brain to exert therapeutic effects.
The human transferrin receptor (TfR1) is universally expressed in different tissues and organs, and the main function of the receptor is to assist transferrin to transport inside and outside cells and blood brain barrier and maintain the iron balance of the cells. Expression levels of TfR1 are significantly higher in tumor cells and in the blood-brain barrier than in normal cell tissues, and therefore, TfR1 is considered as an important target for targeted therapy of tumors and brain diseases. The Chinese patent with the publication number of CN108503704A and the invention name of 'nano drug carrier crossing blood brain barrier' discloses a nano drug carrier crossing blood brain barrier, wherein the carrier can target brain lesions (including brain tumors or other neurodegenerative diseases), the targeted drug carrier crossing blood brain barrier comprises full heavy chain human ferritin or functional fragment reconstruction body or mutant thereof, in the invention, the inventor adopts the full heavy chain human ferritin or the functional fragment thereof as a drug carrier to treat the brain diseases, thereby leading the drug to penetrate the blood brain barrier and improving the curative effect of the drug. However, the method has the defects of complicated preparation method and higher cost.
Disclosure of Invention
In order to solve the above technical problems, the present invention aims to provide a nano-drug and a preparation method thereof, so as to solve the problems in the background art.
In order to achieve the technical effect, the invention adopts the following technical scheme:
the invention provides a nano-drug, comprising: the targeted hydrotalcite nano material comprises a targeted hydrotalcite nano material and an active ingredient loaded on the targeted hydrotalcite nano material, wherein the targeted hydrotalcite nano material comprises a human ferritin heavy chain.
Further, the active ingredient is a drug for preventing/treating ischemic stroke.
Further, the drug is selected from one or more of alteplase, reteplase, lansoprazole, urokinase, clopidogrel, warfarin, dipyridamole, rivaroxate, simvastatin, lovastatin, simvastatin, fluvastatin, pitavastatin, atorvastatin, low molecular dextran and aspirin, and also can be selected from traditional Chinese medicine active ingredients capable of improving microcirculation, such as: extracts or effective components of rhizoma Ligustici Chuanxiong, radix Angelicae sinensis, etc.
Preferably, the drug is atorvastatin.
Meanwhile, the application also claims the application of the nano-drug in the drugs for preventing/treating cerebral arterial thrombosis.
In addition, the invention also provides a preparation method of the nano-drug, which specifically comprises the following steps:
s1: preparing hydrotalcite nano-sheets, and dispersing hydrotalcite nano-materials into deionized water to obtain a hydrotalcite nano-sheet solution; dissolving atorvastatin in deionized water to obtain an atorvastatin aqueous solution, adding the atorvastatin aqueous solution to a hydrotalcite nanosheet solution to obtain a solution A, stirring and reacting for a certain time at room temperature, centrifuging to obtain a precipitate, washing with deionized water for multiple times, and drying to obtain a drug-loaded hydrotalcite nanomaterial loaded with atorvastatin;
s2: synthesizing a heavy chain of ferritin, and preparing a solution B; further dispersing the atorvastatin-loaded drug-loaded hydrotalcite nano material obtained in the step S1 in deionized water to obtain a solution C; and adding a certain amount of the solution B into the solution C, uniformly mixing, incubating for a certain time at a low temperature, centrifuging to collect a solid sample, and repeatedly washing with deionized water to obtain the targeted drug-loaded hydrotalcite nano-drug.
Further, the stirring rotation speed in the step S1 is 10000r/min to 12000r/min, and the stirring time is 8 to 10 min.
Further, in the step S1, the concentration of atorvastatin in the solution a is 0.5mg/ml to 2mg/ml, and the concentration of hydrotalcite nanosheet in the solution a is 0.1mg/ml to 0.3 mg/ml.
Further, the incubation temperature in the step S2 is 2-8 ℃, and the incubation time is 18-20 h.
Compared with the prior art, the invention has the beneficial effects that:
on the first hand, the nano-drug provided by the invention is loaded with the drug by taking LDH as a carrier, has better biocompatibility and lower cytotoxicity, can be loaded with more types of active ingredients and has large drug loading rate, and can carry the drug to pass through the blood brain barrier by combining the targeting effect of the human ferritin heavy chain on the blood brain barrier, so that the treatment effect of the active drug on the ischemic stroke is improved.
In a second aspect, the invention further provides a preparation method of the nano-drug for treating ischemic stroke, the preparation method is simple, the equipment requirement is low, and the treatment cost of ischemic stroke can be effectively reduced.
Drawings
FIG. 1 is a laser speckle imaging picture of a successfully modeled mouse according to example 5 of the present invention;
FIG. 2 is a TTC-stained brain tissue section from four groups of mice, blank group (sham), saline group (saline), LDH group (10mg/kg), and ATO-FTH/Gd-LDH group (10mg/kg), provided in example 6 of the present invention;
FIG. 3 is a brain tissue section of five groups of mice, blank group, normal saline group, LDH group (10mg/kg), Gd-LDH group (10mg/kg), and ATO-FTH/Gd-LDH group (10mg/kg), provided in example 6 of the present invention;
FIG. 4 is a Nissle-stained brain tissue section of five groups of mice, blank group, normal saline group, LDH group (10mg/kg), Gd-LDH group (10mg/kg), and ATO-FTH/Gd-LDH group (10mg/kg), provided in example 6 of the present invention;
FIG. 5 is TUNEL-stained brain tissue sections from five groups of mice, a blank group, a normal saline group, an LDH group (10mg/kg), a Gd-LDH group (10mg/kg), and an ATO-FTH/Gd-LDH group (10mg/kg), provided in example 6 of the present invention;
FIG. 6 shows the expression levels of inflammatory cytokines, including IL- β, MCP-1, IL-6, and TNF- α, in five groups, blank, saline, LDH (10mg/kg), Gd-LDH (10mg/kg), and ATO-FTH/Gd-LDH (10mg/kg), of mice according to example 6 of the present invention.
FIG. 7 shows the difference in the expression levels of MDA, GSH and SOD in five groups of mice, blank group, normal saline group, LDH group (10mg/kg), Gd-LDH group (10mg/kg) and ATO-FTH/Gd-LDH group (10mg/kg), which are provided in example 6 of the present invention.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to the accompanying drawings. The following examples are only for illustrating the technical solutions of the present invention more clearly, and therefore are only examples, and the protection scope of the present invention is not limited thereby.
Example 1 preparation example of drug-loaded hydrotalcite nano-drug targeting for stroke treatment
The method specifically comprises the following steps:
step S1: synthesis of hydrotalcite nano material
Dissolving 1.6mmol of magnesium nitrate hexahydrate and 0.4mol/L of aluminum nitrate nonahydrate in 35mL of water, and performing ultrasonic mixing uniformly to obtain a nitrate solution for later use; dissolving 0.4mmol of sodium nitrate in 40mL of water containing 25% of formamide, carrying out ultrasonic mixing uniformly, then placing the mixture in a three-neck flask, adding a nitrate solution under the stirring of a water bath at 80 ℃, then dropwise adding a NaOH solution with the concentration of 10mg/mL, adjusting the pH to 9, carrying out stirring reaction for 15min, centrifuging by using a centrifugal machine (the rotating speed is 12000r/min, the time is 10min) to obtain a precipitate, washing the precipitate by using deionized water and ethanol, separating, and drying in a drying oven at 60 ℃ for 6h to obtain the hydrotalcite nano material;
step S2: preparation of hydrotalcite nanosheet
Dispersing the hydrotalcite nano material prepared in the step S1 into deionized water to obtain a hydrotalcite nanosheet solution; dissolving atorvastatin in deionized water to obtain an atorvastatin aqueous solution, and adding the atorvastatin aqueous solution to a hydrotalcite nanosheet solution to obtain a solution A. In the solution A, the concentration of the atorvastatin in the solution A is 0.5mg/ml, and the concentration of the hydrotalcite nano-sheets in the solution A is 0.1 mg/ml. Stirring at room temperature (the stirring speed is 10000r/min, and the stirring time is 10min), centrifuging to obtain a precipitate, washing with deionized water for multiple times, and drying to obtain the atorvastatin-loaded drug-loaded hydrotalcite nanomaterial;
step S3: preparation of targeted drug-loaded hydrotalcite nano-drug
Synthesizing a ferritin heavy chain, and preparing a solution B, wherein the concentration of the ferritin heavy chain is 1 mg/ml; further dispersing the medicine-carrying hydrotalcite nano material loaded with atorvastatin obtained in the step S1 in deionized water to obtain a solution C, wherein the concentration of the medicine-carrying hydrotalcite nano material is 0.5 mg/ml; adding the solution B into the solution C according to the ratio of 2:3-8, uniformly mixing, incubating at the low temperature of 2-8 ℃ for 18-20h, centrifuging, collecting a solid sample, and repeatedly washing with deionized water to obtain the targeted drug-loaded hydrotalcite nano-drug.
Example 2 preparation example of drug-loaded hydrotalcite nano-drug targeting for stroke treatment
The method specifically comprises the following steps:
step S1: synthesis of hydrotalcite nano material
Dissolving 1.6mmol of magnesium nitrate hexahydrate and 0.4mol/L of aluminum nitrate nonahydrate in 40mL of water, and performing ultrasonic mixing uniformly to obtain a nitrate solution for later use; dissolving 0.4mmol of sodium nitrate in 40mL of water containing 25% of formamide, carrying out ultrasonic mixing uniformly, then placing the mixture in a three-neck flask, adding a nitrate solution under the stirring of a water bath at 80 ℃, then dropwise adding a NaOH solution with the concentration of 10mg/mL, adjusting the pH to 9, carrying out stirring reaction for 15min, centrifuging by using a centrifugal machine (the rotating speed is 12000r/min, the time is 10min) to obtain a precipitate, washing the precipitate by using deionized water and ethanol, separating, and drying in a drying oven at 55 ℃ for 9h to obtain the hydrotalcite nano material;
step S2: preparation of hydrotalcite nanosheet
Dispersing the hydrotalcite nano material prepared in the step S1 into deionized water to obtain a hydrotalcite nanosheet solution; dissolving atorvastatin in deionized water to obtain an atorvastatin aqueous solution, and adding the atorvastatin aqueous solution to a hydrotalcite nanosheet solution to obtain a solution A. In the solution A, the concentration of the atorvastatin in the solution A is 2mg/ml, and the concentration of the hydrotalcite nano-sheets in the solution A is 0.3 mg/ml. Stirring at room temperature (the stirring speed is 12000r/min, the stirring time is 8min), centrifuging to obtain a precipitate, washing with deionized water for multiple times, and drying to obtain the atorvastatin-loaded drug-loaded hydrotalcite nano material;
step S3: preparation of targeted drug-loaded hydrotalcite nano-drug
Synthesizing a ferritin heavy chain, and preparing a solution B, wherein the concentration of the ferritin heavy chain is 1.2 mg/ml; further dispersing the medicine-carrying hydrotalcite nano material loaded with atorvastatin obtained in the step S1 in deionized water to obtain a solution C, wherein the concentration of the medicine-carrying hydrotalcite nano material is 1 mg/ml; and adding the solution B into the solution C according to the ratio of 1:3, uniformly mixing, incubating at the low temperature of 2-8 ℃ for 18-20h, centrifuging, collecting a solid sample, and repeatedly washing with deionized water to obtain the targeted drug-loaded hydrotalcite nano-drug.
Example 3 preparation example of drug-loaded hydrotalcite nano-drug targeting for stroke treatment
The method specifically comprises the following steps:
step S1: synthesis of hydrotalcite nano material
Dissolving 1.6mmol of magnesium nitrate hexahydrate and 0.4mol/L of aluminum nitrate nonahydrate in 40mL of water, and performing ultrasonic mixing uniformly to obtain a nitrate solution for later use; dissolving 0.4mmol of sodium nitrate in 40mL of water containing 25% of formamide, carrying out ultrasonic mixing uniformly, then placing the mixture in a three-neck flask, adding a nitrate solution under the stirring of a water bath at 80 ℃, then dropwise adding a NaOH solution with the concentration of 10mg/mL, adjusting the pH to 9, carrying out stirring reaction for 15min, centrifuging by using a centrifugal machine (the rotating speed is 12000r/min, the time is 10min) to obtain a precipitate, washing the precipitate by using deionized water and ethanol, separating, and drying in a drying oven at 55 ℃ for 9h to obtain the hydrotalcite nano material;
step S2: preparation of hydrotalcite nanosheet
Dispersing the hydrotalcite nano material prepared in the step S1 into deionized water to obtain a hydrotalcite nanosheet solution; dissolving atorvastatin in deionized water to obtain an atorvastatin aqueous solution, and adding the atorvastatin aqueous solution to a hydrotalcite nanosheet solution to obtain a solution A. In the solution A, the concentration of the atorvastatin in the solution A is 1.5mg/ml, and the concentration of the hydrotalcite nano-sheets in the solution A is 0.2 mg/ml. Stirring at room temperature (the stirring speed is 12000r/min, the stirring time is 9min), centrifuging to obtain a precipitate, washing with deionized water for multiple times, and drying to obtain the atorvastatin-loaded drug-loaded hydrotalcite nano material;
step S3: preparation of targeted drug-loaded hydrotalcite nano-drug
Synthesizing a ferritin heavy chain, and preparing a solution B, wherein the concentration of the ferritin heavy chain is 2 mg/ml; further dispersing the medicine-carrying hydrotalcite nano material loaded with atorvastatin obtained in the step S1 in deionized water to obtain a solution C, wherein the concentration of the medicine-carrying hydrotalcite nano material is 2 mg/ml; and adding the solution B into the solution C according to the ratio of 2:3, uniformly mixing, incubating at the low temperature of 2-8 ℃ for 18-20h, centrifuging, collecting a solid sample, and repeatedly washing with deionized water to obtain the targeted drug-loaded hydrotalcite nano-drug.
Example 4 preparation example of drug-loaded Gd-containing hydrotalcite nano-drug for treating cerebral apoplexy
The method specifically comprises the following steps:
step S1: synthesis of hydrotalcite nano material
Dissolving 1.6mmol of magnesium nitrate hexahydrate, 0.32mol/L of aluminum nitrate nonahydrate and 0.08mmol of gadolinium nitrate hexahydrate in 40mL of water, and uniformly mixing by ultrasonic waves to obtain a nitrate solution for later use; dissolving 0.4mmol of sodium nitrate in 40mL of water containing 25% of formamide, carrying out ultrasonic mixing uniformly, then placing the mixture in a three-neck flask, adding a nitrate solution under the stirring of a water bath at 80 ℃, then dropwise adding a NaOH solution with the concentration of 10mg/mL, adjusting the pH to 9, carrying out stirring reaction for 15min, centrifuging by using a centrifugal machine (the rotating speed is 12000r/min, the time is 10min) to obtain a precipitate, washing the precipitate by using deionized water and ethanol, separating, and drying in a drying oven at 55 ℃ for 9h to obtain the hydrotalcite nano material;
step S2: preparation of hydrotalcite nanosheet
Dispersing the hydrotalcite nano material prepared in the step S1 into deionized water to obtain a hydrotalcite nanosheet solution; dissolving atorvastatin in deionized water to obtain an atorvastatin aqueous solution, and adding the atorvastatin aqueous solution to a hydrotalcite nanosheet solution to obtain a solution A. In the solution A, the concentration of the atorvastatin in the solution A is 2mg/ml, and the concentration of the hydrotalcite nano-sheets in the solution A is 0.3 mg/ml. Stirring at room temperature (the stirring speed is 12000r/min, the stirring time is 8min), centrifuging to obtain a precipitate, washing with deionized water for multiple times, and drying to obtain the atorvastatin-loaded drug-loaded hydrotalcite nano material;
step S3: preparation of targeted drug-loaded hydrotalcite nano-drug
Synthesizing a ferritin heavy chain, and preparing a solution B, wherein the concentration of the ferritin heavy chain is 1.2 mg/ml; further dispersing the medicine-carrying hydrotalcite nano material loaded with atorvastatin obtained in the step S1 in deionized water to obtain a solution C, wherein the concentration of the medicine-carrying hydrotalcite nano material is 1 mg/ml; and adding the solution B into the solution C according to the ratio of 1:3, uniformly mixing, incubating at the low temperature of 2-8 ℃ for 18-20h, centrifuging, collecting a solid sample, and repeatedly washing with deionized water to obtain the targeted drug-loaded hydrotalcite nano-drug.
EXAMPLE 5 modeling of laboratory animals
MCAO model mice were made by inserting a wire plug with a silicone tip into the bifurcation of the distal middle cerebral artery and anterior cerebral artery of the internal carotid artery of C57BL/6 mice for 90 minutes, and then withdrawing the wire plug to form reperfusion. A sham-operated group was established, consistent with treatment with the MCAO model except for embolisms. The MCAO model mice were randomly divided into four groups, including the saline group, the LDH group (10mg/kg), the Gd-LDH group (10mg/kg), and the ATO-ferritin/Gd-LDH group (10mg/kg) (3 mice each). After the operation is finished, monitoring cerebral blood flow of the mouse by using a laser speckle blood flow imager, and when the cerebral blood flow is reduced by 70-80%, indicating that the model is successfully prepared, wherein a blood flow detection experimental result of the mouse which is successfully modeled is shown in figure 1.
Example 6 animal Experimental procedures
All LDH, Gd-LDH, ATO-ferritin/Gd-LDH samples prepared in example 4 were dispersed in saline solution and mice were injected tail vein with drug within 1h after perfusion.
Example 7 results of the experiment
(1) After 3 days of successful modeling, each group of mice was sacrificed, brain tissue of the mice was removed and washed three times with saline, and then the brain tissue was cut into five 2mm brain tissue sections, which were added to PBS containing 2% TTC and incubated at 37 ℃ for 20 minutes. After TTC staining, brain sections were fixed in 4% paraformaldehyde solution for photographing, and the experimental results are shown in fig. 2.
(2) The obtained brain tissue sections of mice were subjected to H & E staining, Nissl staining and TUNEL Hoechst staining, and the experimental results corresponded to FIG. 3, FIG. 4 and FIG. 5, respectively.
(3) ELISA detects the expression levels of a plurality of evaluation indexes in mice, wherein the evaluation indexes comprise the expression levels of IL-beta, MCP-1, IL-6, TNF-alpha, MDA, GSH and SOD, the expression levels of IL-beta, MCP-1, IL-6 and TNF-alpha are shown in figure 6, and the expression levels of MDA, GSH and SOD are shown in figure 7 (the experimental data are statistically processed by SPSS 16.0 software).
Although the present invention has been described in detail with reference to the preferred embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the spirit and scope of the invention as defined in the appended claims. The techniques, shapes, and configurations not described in detail in the present invention are all known techniques.
Claims (9)
1. A nano-drug, comprising: the targeted hydrotalcite nano material comprises a targeted hydrotalcite nano material and an active ingredient loaded on the targeted hydrotalcite nano material, wherein the targeted hydrotalcite nano material comprises a human ferritin heavy chain.
2. The nano-drug of claim 1, wherein: the active ingredient is a medicament for preventing/treating ischemic stroke.
3. The nano-drug of claim 2, wherein: the medicine is selected from one or more of alteplase, reteplase, lansoprazole, urokinase, chloriblegrel, warfarin, pyridagains, rivaroxaban, simvastatin, lovastatin, simvastatin, fluvastatin, pitavastatin, atorvastatin, low molecular dextran and aspirin.
4. The nano-drug of claim 2, wherein: the drug is atorvastatin.
5. The use of a nano-drug as in any one of claims 1-4 in the preparation of a medicament for the prevention/treatment of stroke.
6. The method of claim 1, comprising:
step S1: preparing hydrotalcite nano-sheets, and dispersing hydrotalcite nano-materials into deionized water to obtain a hydrotalcite nano-sheet solution; dissolving atorvastatin in deionized water to obtain an atorvastatin aqueous solution, adding the atorvastatin aqueous solution to a hydrotalcite nanosheet solution to obtain a solution A, stirring and reacting for a certain time at room temperature, centrifuging to obtain a precipitate, washing with deionized water for multiple times, and drying to obtain a drug-loaded hydrotalcite nanomaterial loaded with atorvastatin;
step S2: synthesizing a heavy chain of ferritin, and preparing a solution B; further dispersing the atorvastatin-loaded drug-loaded hydrotalcite nano material obtained in the step S1 in deionized water to obtain a solution C; and adding a certain amount of the solution B into the solution C, uniformly mixing, incubating for a certain time at a low temperature, centrifuging to collect a solid sample, and repeatedly washing with deionized water to obtain the targeted drug-loaded hydrotalcite nano-drug.
7. The method of claim 6, wherein the step of preparing the nano-drug comprises: the stirring speed in the step S1 is 10000r/min-12000r/min, and the stirring time is 8-10 min.
8. The method of claim 6, wherein the step of preparing the nano-drug comprises: in the step S1, the concentration of atorvastatin in the solution A is 0.5mg/ml-2mg/ml, and the concentration of hydrotalcite nano-sheets in the solution A is 0.1mg/ml-0.3 mg/ml.
9. The method of claim 6, wherein the step of preparing the nano-drug comprises: the incubation temperature in the step S2 is 2-8 ℃, and the incubation time is 18-20 h.
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