CN115252876A - Monodisperse luminescent developing drug-loading four-in-one embolic microsphere and preparation method thereof - Google Patents
Monodisperse luminescent developing drug-loading four-in-one embolic microsphere and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 28
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- 238000004519 manufacturing process Methods 0.000 claims abstract 2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/02—Use of particular materials as binders, particle coatings or suspension media therefor
- C09K11/025—Use of particular materials as binders, particle coatings or suspension media therefor non-luminescent particle coatings or suspension media
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Abstract
The invention discloses a particle size monodisperse luminescent developing drug-loading four-in-one embolism microsphere and a preparation method thereof. The microsphere integrates the functions of embolism, near-infrared visible light, X-ray development and tumor resistance, and can be used for embolizing tumors or stopping bleeding and other diseases. The method has the advantages of simple process flow, low production cost, good repeatability and easy large-scale production, and the particle size of the microspheres is monodisperse and is regulated and controlled by controlling the proportion of the disperse phase and the continuous phase.
Description
Technical Field
The invention relates to a preparation method of a four-in-one polyethylene glycol diacrylate embolism microsphere, in particular to a monodisperse drug-loaded embolism microsphere which can emit light in a near-infrared region and can be developed under X-rays and a preparation method thereof.
Background
Cancer is one of the most difficult multiple diseases to cure at present, and irregular living habits gradually occupy lives of people along with the increasing pace of life. The main treatment methods of cancer mainly comprise surgical excision, chemotherapy and the like. However, both of these methods cause intuitive irreversible damage to the body, and the corresponding side effects can also compromise the body's safety. Direct resection not only has the potential to cause massive hemorrhage but also can easily induce postoperative metastasis, and the same chemotherapy treatment completely kills cancer cells but also has little damage to normal cells, which is called as one-thousand damage to eight-hundred. The transcatheter arterial embolization operation is mainly characterized by that the embolizing agent is injected into the supply blood vessel of pathological target organ by means of arterial or intravenous catheter to make the blood vessel produce occlusion, interrupt blood supply and "starve" target cell so as to finally attain the goal of treatment.
Besides blocking blood vessels, the embolic emulsion is mixed with chemotherapeutic drugs, so that the drugs are released to the tumor while essential nutrients are blocked from being delivered to the tumor, and the tumor is killed to achieve the effect of dual-tube. Compared with the traditional method, the tumor interventional therapy has the advantages of minimal invasion, low cost, safety, good curative effect and the like, and has important significance for tumor patients who cannot be operated. This is a palliative treatment for patients with middle and advanced stage cancer or for those who cannot use surgical removal of tumors; secondly, for the people who have too large tumor and are not suitable for operation, the operation excision can be carried out after the tumor is reduced through the catheter arterial embolization operation; in addition, it can be used for intra-arterial perfusion chemotherapy for preventing recurrence after tumor resection.
At present, no monodisperse embolic agent with near-infrared two-region visible and X-ray development, drug loading and embolization functions simultaneously provides guarantee for accurate positioning and backflow prevention in the embolization process and provides support for avoiding postoperative massive hemorrhage and focus metastasis.
Disclosure of Invention
The invention aims to provide a preparation method of a luminescent development drug-loading four-in-one polyethylene glycol diacrylate embolism microsphere with monodisperse particle size and good biocompatibility.
The technical scheme of the invention comprises the following steps:
a preparation method of a luminescent developing medicine-carrying four-in-one polyethylene glycol diacrylate embolism microsphere comprises the following steps:
s1, adding a photoinitiator 2-hydroxy-2-methyl-1-phenyl-1-acetone into polyethylene glycol diacrylate to obtain a mixed solution;
s2, dispersing the adriamycin, barium sulfate nano powder and silver sulfide quantum dots in the mixed solution, and uniformly mixing by ultrasonic for 30 min;
and S3, sucking the obtained mixed solution into an injector, placing the mixed solution on a microflow pump to serve as a dispersion phase, sucking the dimethyl silicone oil into the injector, placing the dimethyl silicone oil into another microflow pump to serve as a continuous phase, generating liquid drops by utilizing shearing action, initiating polymerization reaction through ultraviolet light action, solidifying the liquid drops, and washing the liquid drops for multiple times through a demulsifier and distilled water to obtain the monodisperse luminescent developing medicine-carrying embolism microsphere.
In the preparation method, in step S1, a photoinitiator is dissolved in polyethylene glycol diacrylate at room temperature to obtain 90-95% (wt%) of polyethylene glycol diacrylate solution.
The preparation method comprises the step S1 of absorbing light energy after the added photoinitiator is irradiated by ultraviolet light, splitting the light energy into 2 active free radicals and initiating PEG-DA to generate chain polymerization crosslinking curing, and is characterized by being rapid, environment-friendly and energy-saving
In the preparation method, in the step S2, according to the different solubility and luminescence degrees of silver sulfide and barium sulfate, the ratio of the dosage by mass of the barium sulfate powder to the dosage by mass of the silver sulfide quantum dots is controlled to be 30-10.
In the preparation method, in step S2, the mass ratio of the barium sulfate powder to PEG-DA is controlled to be 1.
According to the preparation method, in the step S2, the dosage mass ratio of the adriamycin to the PEG-DA is controlled to be 1.
In the preparation method, in the step S3, the flow rate of the water phase is 2-20 mu L/min and the flow rate of the oil phase is 50-200 mu L/min.
In the preparation method, in the step S3, a 365nm ultraviolet light source is selected.
In the preparation method, in step S3, the washing is: washed 3 times with 1% Triton X-100 in water, rinsed thoroughly with distilled water and dried in vacuo.
The luminous developing medicine-carrying four-in-one polyethylene glycol diacrylate embolism microsphere prepared by any preparation method has the advantages that the polyethylene glycol diacrylate wraps an anti-tumor medicine, a near-infrared two-region luminous material and an X-ray developing material to form a microsphere structure, and has four functions of embolism, tumor resistance, luminescence and development.
The particle size distribution of the luminous developing medicine-carrying four-in-one polyethylene glycol diacrylate embolism microsphere is in a narrow range of 100-1200 mu m, and the luminous developing medicine-carrying four-in-one polyethylene glycol diacrylate embolism microsphere has a monodispersity.
Compared with the prior art, the invention has the advantages that:
(1) The method comprises the steps of loading an anti-tumor drug, a near-infrared two-region luminescent material and an X-ray developer into polyethylene glycol diacrylate by a microfluidic technology, quickly and accurately forming liquid drops with required particle size through shearing action, and quickly initiating crosslinking and curing through ultraviolet light to directly obtain the four-in-one embolism microsphere.
(2) The four-in-one embolism microsphere prepared by the method can emit light in a near infrared region due to the action of the silver sulfide quantum dots, and can be developed under X-rays due to the existence of barium sulfate, so that the four-in-one embolism microsphere is more widely applied and can be positioned better and accurately due to the cooperation of the silver sulfide quantum dots and the barium sulfate;
(3) The four-in-one embolism microsphere prepared by the invention has good biocompatibility, wide controllable range of particle size, monodispersity of particle size and better embolism; has better biocompatibility and is more beneficial to clinical application.
Drawings
FIG. 1 is a microscopic image of a four-in-one polyethylene glycol diacrylate embolic microsphere obtained in example 1;
FIG. 2 is a near infrared two-region luminescence image of the four-in-one PEG-diacrylate embolic microsphere obtained in example 1;
FIG. 3 is a photograph of an X-ray developed four-in-one PEG-diacrylate embolic microsphere obtained in example 1.
FIG. 4 is a graph showing the data on the cell viability of the four-in-one PEG-diacrylate embolized microspheres obtained in example 1.
FIG. 5 is a diagram showing the survival and death of cells in the case where the four-in-one polyethylene glycol diacrylate embolized microspheres obtained in example 1 were incubated with normal cells.
Detailed Description
The present invention will be described in detail with reference to specific examples.
The microsphere morphology was measured by OLYMPU SCKX53 inverted fluorescence microscope.
The near infrared two-region luminescence data is measured by a UniNano-NIR II type near infrared two-region imager.
The X-ray development data were measured by an IVIS Lumina XRMS model small animal in vivo imager.
Cytotoxicity data were measured by SpectraMax M3 microplate reader.
The data of cell viability were measured by OLYMPU SCKX53 inverted fluorescence microscope.
Example 1
Preparation of microspheres
Mixing 0.3g of photoinitiator 2-hydroxy-2-methyl-1-phenyl-1-propanone into 10g of polyethylene glycol diacrylate (Mw = 575) at room temperature to obtain a polyethylene glycol diacrylate mixed solution, dispersing 5mg of doxorubicin into the mixed solution, dispersing 1g of nano-sized barium sulfate powder into the mixed solution, dispersing 0.1g of silver sulfide quantum dots into the mixed solution, and performing ultrasonic treatment for 30min to form a uniform mixed solution. The resulting mixed droplets were then drawn into a syringe and placed on a microflow pump as the aqueous phase (dispersed phase). Then, an injector with the same specification is used for sucking the dimethyl silicone oil and is arranged on a microflow pump with the same specification to be used as an oil phase (continuous phase), a transparent hose is used for connecting a channel with an injector needle, the flow rate of a disperse phase is set to be 2 mu L/min-5 mu L/min, the flow rate of the continuous phase is set to be 200 mu L/min, liquid drops are formed through shearing action, the particle size of the obtained microspheres is in direct proportion to the flow rate of the disperse phase and in inverse proportion to the flow rate of the continuous phase, and the microspheres with different particle sizes are obtained by adjusting the flow rate proportion of the disperse phase and the continuous phase. 365nm ultraviolet light is applied to the upper part of the collecting channel, and the embolism microsphere can be obtained by crosslinking within 5 s. Washing with 1% Triton X-100 water solution for 3 times, rinsing with distilled water, and vacuum drying.
The flow rate of the liquid of the dispersed phase and the continuous phase is adjusted to obtain the microspheres with different particle sizes.
Micro-ball microscope
The microspheres prepared in this example were dried, sieved, and observed under an inverted fluorescence microscope. The result shows that the microsphere prepared by the embodiment has monodispersity and good sphericity, and the surface of the microsphere with the polydispersion distributed in a range of 100-300 mu m is smooth.
Near infrared two-zone visible light emitting effect
The microspheres prepared in this example and ordinary polyethylene glycol diacrylate microspheres were separately loaded into an EP tube, and the luminescence was observed with a near-infrared two-zone small animal imaging instrument. The result shows that the microsphere prepared in the embodiment has obvious luminescence in the near infrared region II, and the common polyethylene glycol diacrylate microsphere does not emit luminescence.
Luminous effect under X-ray
The microspheres prepared in this example and ordinary polyethylene glycol diacrylate microspheres were separately loaded into an EP tube and observed for luminescence under an X-ray small animal imaging instrument. The results show that the microspheres prepared in this example are developable under X-rays, and that ordinary polyethylene glycol diacrylate microspheres are not developable under X-rays.
Cytotoxicity
The microspheres prepared in the example were tested for cytotoxicity using the MTT method, and were incubated in cells for 24, 48, and 72 hours, respectively, and the viability of the cells was measured using a microplate reader, followed by AM/PI staining and observation of cell viability under an inverted fluorescence microscope. The result shows that the microsphere prepared by the embodiment has almost no cytotoxicity except the cytotoxicity of the adriamycin, the cell survival rate is higher, and the biocompatibility is better.
FIG. 1 is a microscopic image of the tetrad-in-one PEG-diacrylate embolic microsphere obtained in example 1, which shows that the microsphere has monodispersity, good sphericity and smooth and uniform sphere;
fig. 2 is a near-infrared two-region luminescence diagram of the four-in-one peg diacrylate embolization microspheres obtained in example 1, which shows that the four-in-one peg diacrylate embolization microspheres have stronger luminescence and visibility in the near-infrared two regions than the conventional peg diacrylate microspheres;
FIG. 3 is a photograph of an X-ray development of the four-in-one PEG-diacrylate embolic microsphere obtained in example 1, which shows that the four-in-one PEG-diacrylate embolic microsphere is easier to develop and more visible under X-ray than a conventional PEG-diacrylate microsphere;
FIGS. 4 and 5 are the cytotoxicity data of the four-in-one PEG-diacrylate embolic microspheres obtained in example 1, and the cell survival data of FIG. 4; FIG. 5 shows the data of viable and dead cells, and it can be seen that the viability of the cells in the microsphere incubation is good except for the cytotoxicity of adriamycin, and almost no cytotoxicity exists.
Example 2
Preparation of microspheres
Mixing 0.3g of photoinitiator 2-hydroxy-2-methyl-1-phenyl-1-propanone into 10g of polyethylene glycol diacrylate (Mw = 575) at room temperature to obtain a polyethylene glycol diacrylate mixed solution, dispersing 5mg of doxorubicin into the mixed solution, dispersing 0.5g of nanoscale barium sulfate powder into the mixed solution, dispersing 0.1g of silver sulfide quantum dots into the mixed solution, and performing ultrasonic treatment for 30min to form a uniform mixed solution. The resulting mixed droplets were then drawn into a syringe and placed on a microflow pump as the aqueous phase (dispersed phase). Then, an injector with the same specification is used for sucking the dimethyl silicone oil and is arranged on a microflow pump with the same specification to be used as an oil phase (continuous phase), a transparent hose is used for connecting a channel with an injector needle, the flow rate of a disperse phase is set to be 2 mu L/min-5 mu L/min, the flow rate of the continuous phase is set to be 200 mu L/min, liquid drops are formed through shearing action, the particle size of the obtained microspheres is in direct proportion to the flow rate of the disperse phase and in inverse proportion to the flow rate of the continuous phase, and the microspheres with different particle sizes are obtained by adjusting the flow rate proportion of the disperse phase and the continuous phase. 365nm ultraviolet light is applied on the upper part of the collecting channel, and the embolism microsphere can be obtained by crosslinking within 5 s. Washing with 1% Triton (Triton X-100) water solution for 3 times, rinsing with distilled water, and vacuum drying.
The flow rate of the liquid of the dispersed phase and the continuous phase is adjusted to obtain the microspheres with different grain diameters.
Micro-ball microscope
The morphology of the microspheres was measured in the same manner as in example 1, and the results showed that the microspheres had monodisperse particle sizes, which were the same as in example 1 and were mostly distributed in the range of 300 to 500. Mu.m.
Near infrared two-zone visible light emitting effect
The light emission effect in the near-infrared region two was measured in the same manner as in example 1, and the light emission effect was found to be good as in example 1.
Luminous effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good, but the degree of luminescence was slightly lower than in example 1.
Cytotoxicity
The cytotoxicity of the microspheres was measured in the same manner as in example 1, and the results showed that the biocompatibility of the microspheres was good.
Example 3
Preparation of microspheres
0.3g of photoinitiator 2-hydroxy-2-methyl-1-phenyl-1-propanone was mixed into 10g of polyethylene glycol diacrylate (Mw = 575) at room temperature to obtain a polyethylene glycol diacrylate mixed solution, 5mg of doxorubicin was dispersed in the mixed solution, 1g of nano-sized barium sulfate powder was dispersed in the mixed solution, 0.05g of silver sulfide quantum dots was dispersed in the mixed solution, and a uniform mixed solution was formed by ultrasonication for 30 min. The resulting mixed droplets were then drawn into a syringe and placed on a microflow pump as the aqueous phase (dispersed phase). And then, sucking the dimethyl silicone oil by using an injector with the same specification, placing the dimethyl silicone oil on a microflow pump with the same specification as an oil phase (continuous phase), connecting a channel by using a transparent hose and an injector needle, setting the flow rate of a disperse phase to be 2-5 mu L/min and the flow rate of the continuous phase to be 200 mu L/min, forming liquid drops through shearing action, wherein the particle size of the obtained microspheres is in direct proportion to the flow rate of the disperse phase and in inverse proportion to the flow rate of the continuous phase, and the microspheres with different particle sizes are obtained by adjusting the flow rate proportion of the disperse phase to the continuous phase. 365nm ultraviolet light is applied to the upper part of the collecting channel, and the embolism microsphere can be obtained by crosslinking within 5 s. Washing with 1% Triton X-100 water solution for 3 times, rinsing with distilled water, and vacuum drying.
The flow rate of the liquid of the dispersed phase and the continuous phase is adjusted to obtain the microspheres with different grain diameters.
Micro-ball microscope
The morphology of the microspheres was measured in the same manner as in example 1, and the results showed that the microspheres had monodisperse particle sizes, which were the same as in example 1 and were mostly distributed in the range of 300 to 500. Mu.m.
Near-infrared two-region visible light emitting effect
The light emission effect in the near-infrared region two was measured in the same manner as in example 1, and the result showed that the light emission effect was good, but the light emission level was lower than that in example 1.
Luminous effect under X-ray
The same procedure as in example 1 was repeated except that the developing effect under X-ray irradiation was measured, and the result showed that the developing effect was excellent.
Cytotoxicity
The cytotoxicity of the microspheres was measured in the same manner as in example 1, and the results showed that the biocompatibility of the microspheres was good.
Example 4
Preparation of microspheres
Mixing 0.3g of photoinitiator 2-hydroxy-2-methyl-1-phenyl-1-propanone into 10g of polyethylene glycol diacrylate (Mw = 575) at room temperature to obtain a polyethylene glycol diacrylate mixed solution, dispersing 5mg of doxorubicin into the mixed solution, dispersing 1g of nano-sized barium sulfate powder into the mixed solution, dispersing 0.1g of silver sulfide quantum dots into the mixed solution, and performing ultrasonic treatment for 30min to form a uniform mixed solution. The resulting mixed droplets were then drawn into a syringe and placed on a microflow pump as the aqueous phase (dispersed phase). And then, sucking the dimethyl silicone oil by using an injector with the same specification, placing the dimethyl silicone oil on a microflow pump with the same specification as an oil phase (continuous phase), connecting a channel by using a transparent hose and an injector needle, setting the flow rate of a dispersed phase to be 5 mu L/min, setting the flow rate of the continuous phase to be 150 mu L/min-200 mu L/min, forming liquid drops through shearing action, wherein the particle size of the obtained microspheres is in direct proportion to the flow rate of the dispersed phase and in inverse proportion to the flow rate of the continuous phase, and the microspheres with different particle sizes are obtained by adjusting the flow rate proportion of the dispersed phase to the flow rate of the continuous phase. 365nm ultraviolet light is applied to the upper part of the collecting channel, and the embolism microsphere can be obtained by crosslinking within 5 s. Washing with 1% Triton (Triton X-100) water solution for 3 times, rinsing with distilled water, and vacuum drying.
The flow rate of the liquid of the dispersed phase and the continuous phase is adjusted to obtain the microspheres with different grain diameters.
Micro-ball microscope
The morphology of the microspheres was measured in the same manner as in example 1, and the results showed that the particle diameters of the microspheres were monodisperse and had a polydispersity in the range of 300-500. Mu.m.
Near-infrared two-region visible light emitting effect
The light emission effect in the near-infrared region two was measured in the same manner as in example 1, and the result showed that the light emission effect was good.
Luminous effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Cytotoxicity
The cytotoxicity of the microspheres was measured in the same manner as in example 1, and the results showed that the biocompatibility of the microspheres was good.
Example 5
Preparation of microspheres
Mixing 0.3g of photoinitiator 2-hydroxy-2-methyl-1-phenyl-1-propanone into 10g of polyethylene glycol diacrylate (Mw = 575) at room temperature to obtain a polyethylene glycol diacrylate mixed solution, dispersing 5mg of doxorubicin into the mixed solution, dispersing 1g of nano-sized barium sulfate powder into the mixed solution, dispersing 0.1g of silver sulfide quantum dots into the mixed solution, and performing ultrasonic treatment for 30min to form a uniform mixed solution. The resulting mixed droplets were then drawn into a syringe and placed on a microflow pump as the aqueous phase (dispersed phase). And then, sucking the dimethyl silicone oil by using an injector with the same specification, placing the dimethyl silicone oil on a microflow pump with the same specification as an oil phase (continuous phase), connecting a channel by using a transparent hose and an injector needle, setting the flow rate of a dispersed phase to be 10 mu L/min, setting the flow rate of the continuous phase to be 100 mu L/min-150 mu L/min, forming liquid drops through shearing action, wherein the particle size of the obtained microspheres is in direct proportion to the flow rate of the dispersed phase and in inverse proportion to the flow rate of the continuous phase, and the microspheres with different particle sizes are obtained by adjusting the flow rate proportion of the dispersed phase to the flow rate of the continuous phase. 365nm ultraviolet light is applied to the upper part of the collecting channel, and the embolism microsphere can be obtained by crosslinking within 5 s. Washing with 1% Triton (Triton X-100) water solution for 3 times, rinsing with distilled water, and vacuum drying.
The flow rate of the liquid of the dispersed phase and the continuous phase is adjusted to obtain the microspheres with different particle sizes.
Micro-ball microscope
The morphology of the microspheres was measured in the same manner as in example 1, and the results showed that the particle size distribution was good, and was mostly in the range of 500 to 700. Mu.m.
Near-infrared two-region visible light emitting effect
The light emission effect in the near-infrared region two was measured in the same manner as in example 1, and the result showed that the light emission effect was good.
Luminous effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Cytotoxicity
The cytotoxicity of the microspheres was measured in the same manner as in example 1, and the results showed that the biocompatibility of the microspheres was good.
Example 6
Preparation of microspheres
Mixing 0.3g of photoinitiator 2-hydroxy-2-methyl-1-phenyl-1-propanone into 10g of polyethylene glycol diacrylate (Mw = 575) at room temperature to obtain a polyethylene glycol diacrylate mixed solution, dispersing 5mg of doxorubicin into the mixed solution, dispersing 1g of nano-sized barium sulfate powder into the mixed solution, dispersing 0.1g of silver sulfide quantum dots into the mixed solution, and performing ultrasonic treatment for 30min to form a uniform mixed solution. The resulting mixed droplets were then drawn into a syringe and placed on a microflow pump as the aqueous phase (dispersed phase). And then, sucking the dimethyl silicone oil by using an injector with the same specification, placing the dimethyl silicone oil on a microflow pump with the same specification as an oil phase (continuous phase), connecting a channel by using a transparent hose and an injector needle, setting the flow rate of a dispersed phase to be 15 mu L/min, setting the flow rate of the continuous phase to be 100 mu L/min-150 mu L/min, forming liquid drops through shearing action, wherein the particle size of the obtained microspheres is in direct proportion to the flow rate of the dispersed phase and in inverse proportion to the flow rate of the continuous phase, and the microspheres with different particle sizes are obtained by adjusting the flow rate proportion of the dispersed phase to the flow rate of the continuous phase. 365nm ultraviolet light is applied to the upper part of the collecting channel, and the embolism microsphere can be obtained by crosslinking within 5 s. Washing with 1% Triton X-100 water solution for 3 times, rinsing with distilled water, and vacuum drying.
The flow rate of the liquid of the dispersed phase and the continuous phase is adjusted to obtain the microspheres with different particle sizes.
Micro-ball microscope
The morphology of the microspheres was measured in the same manner as in example 1, and the results showed that the particle size distribution was good, and was mostly in the range of 700 to 900. Mu.m.
Near-infrared two-region visible light emitting effect
The light emission effect in the near-infrared region two was measured in the same manner as in example 1, and the result showed that the light emission effect was good.
Luminous effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Cytotoxicity
The cytotoxicity of the microspheres was measured in the same manner as in example 1, and the results showed that the biocompatibility of the microspheres was good.
Example 7
Preparation of microspheres
0.3g of photoinitiator 2-hydroxy-2-methyl-1-phenyl-1-propanone was mixed into 10g of polyethylene glycol diacrylate (Mw = 575) at room temperature to obtain a polyethylene glycol diacrylate mixed solution, 5mg of doxorubicin was dispersed in the mixed solution, 1g of nano-sized barium sulfate powder was dispersed in the mixed solution, 0.1g of silver sulfide quantum dots was dispersed in the mixed solution, and a uniform mixed solution was formed by ultrasound for 30 min. The resulting mixed droplets were then drawn into a syringe and placed on a microflow pump as the aqueous phase (dispersed phase). And then, sucking the dimethyl silicone oil by using an injector with the same specification, placing the dimethyl silicone oil on a microflow pump with the same specification as an oil phase (continuous phase), connecting a channel by using a transparent hose and an injector needle, setting the flow rate of a dispersed phase to be 20 mu L/min, setting the flow rate of the continuous phase to be 50 mu L/min-100 mu L/min, forming liquid drops through shearing action, wherein the particle size of the obtained microspheres is in direct proportion to the flow rate of the dispersed phase and in inverse proportion to the flow rate of the continuous phase, and the microspheres with different particle sizes are obtained by adjusting the flow rate proportion of the dispersed phase to the flow rate of the continuous phase. 365nm ultraviolet light is applied on the upper part of the collecting channel, and the embolism microsphere can be obtained by crosslinking within 5 s. Washing with 1% Triton X-100 water solution for 3 times, rinsing with distilled water, and vacuum drying.
The flow rate of the liquid of the dispersed phase and the continuous phase is adjusted to obtain the microspheres with different grain diameters.
Micro-ball microscope
The morphology of the microspheres was measured in the same manner as in example 1, and the results showed that the particle size distribution was good and was mostly in the range of 900 to 1200. Mu.m.
Near-infrared two-region visible light emitting effect
The luminous effect in the near-infrared region two was measured in the same manner as in example 1, and the result showed that the luminous effect was good.
Luminous effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Cytotoxicity
The cytotoxicity of the microspheres was measured in the same manner as in example 1, and the results showed that the biocompatibility of the microspheres was good.
It will be understood that modifications and variations can be made by persons skilled in the art in light of the above teachings and all such modifications and variations are intended to be included within the scope of the invention as defined in the appended claims.
Claims (10)
1. A preparation method of a particle size monodisperse luminescent developing drug-loading four-in-one embolism microsphere is characterized by comprising the following steps:
s1, adding a photoinitiator 2-hydroxy-2-methyl-1-phenyl-1-acetone into polyethylene glycol diacrylate (PEG-DA) to obtain a mixed solution;
s2, dispersing the adriamycin, the barium sulfate nano powder and the silver sulfide quantum dots in the mixed solution, and uniformly mixing by ultrasonic;
s3, sucking the obtained mixed solution into an injector, placing the mixed solution on a microflow pump to serve as a dispersion phase, sucking dimethyl silicone oil into the injector, placing the dimethyl silicone oil into another microflow pump to serve as an oil phase, generating liquid drops by utilizing shearing action, initiating polymerization reaction through ultraviolet light action, solidifying the liquid drops, and washing the liquid drops for multiple times through a demulsifier and distilled water to obtain the monodisperse luminescent developing medicine-carrying embolism microsphere.
2. The method of claim 1, wherein the photoinitiator is added to the polyethylene glycol diacrylate (Mw = 575) at room temperature in 3% (wt%) in step S1 to obtain a 90-95% (wt%) PEG-DA solution.
3. The preparation method of claim 1, wherein in step S1, the added photoinitiator absorbs light energy after being irradiated by ultraviolet light, and splits the light energy into 2 active radicals to initiate chain polymerization, crosslinking and curing of PEG-DA, which is characterized by rapidness, environmental protection and energy saving.
4. The preparation method according to claim 1, wherein in step S2, the mass ratio of the barium sulfate powder to the silver sulfide quantum dots is controlled to be 30; according to the sedimentation velocity of barium sulfate, the mass ratio of barium sulfate powder to PEG-DA is controlled to be 1.
5. The preparation method according to claim 1, wherein in step S2, the mass ratio of the doxorubicin to the PEG-DA is controlled to 1.
6. The production method according to claim 1, wherein in step S3, the flow rate of the aqueous phase is 2 μ L/min to 20 μ L/min and the flow rate of the oil phase is 50 μ L/min to 200 μ L/min.
7. The method according to claim 1, wherein in step S3, a 365nm uv light source is selected.
8. The method according to claim 1, wherein in step S3, the washing is: washed 3 times with 1% aqueous Triton (Triton X-100) solution, rinsed thoroughly with distilled water, and dried in vacuo.
9. The monodisperse luminescent and developing drug-loaded four-in-one embolic microsphere prepared by the preparation method according to any one of claims 1 to 8, wherein the polyethylene glycol diacrylate wraps the anti-tumor drug, the near-infrared two-region luminescent material and the developing material under X-ray to form a microsphere structure, and has four functions of embolization, luminescence, development and anti-tumor.
10. The monodisperse luminescent-developable drug-loaded four-in-one embolic microsphere of claim 9, wherein the particle size thereof can be controlled and distributed in any range of 100-1200 μm and the microsphere corresponding to a determined flow rate has monodisperse properties.
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