CN112618517B - Preparation method of P/H microspheres wrapped with hydrophobic solid powder - Google Patents

Preparation method of P/H microspheres wrapped with hydrophobic solid powder Download PDF

Info

Publication number
CN112618517B
CN112618517B CN202011471957.6A CN202011471957A CN112618517B CN 112618517 B CN112618517 B CN 112618517B CN 202011471957 A CN202011471957 A CN 202011471957A CN 112618517 B CN112618517 B CN 112618517B
Authority
CN
China
Prior art keywords
hydrogel
microspheres
solid powder
powder
bubbles
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202011471957.6A
Other languages
Chinese (zh)
Other versions
CN112618517A (en
Inventor
许忠斌
刘聪
黄兴
郑素霞
徐宁涛
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhejiang University ZJU
Original Assignee
Zhejiang University ZJU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhejiang University ZJU filed Critical Zhejiang University ZJU
Priority to CN202011471957.6A priority Critical patent/CN112618517B/en
Publication of CN112618517A publication Critical patent/CN112618517A/en
Application granted granted Critical
Publication of CN112618517B publication Critical patent/CN112618517B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5089—Processes

Abstract

The invention discloses a preparation method of P/H microspheres wrapped with hydrophobic solid powder, which comprises the following steps: (1) placing a hydrophobic solid powder on the surface of the hydrogel solution; (2) immersing a frame for generating bubbles into the hydrogel solution with the surface provided with the solid powder, and then lifting the frame from the hydrogel solution, wherein a layer of hydrogel liquid film is attached to the frame; with the rising of the frame, the liquid film is continuously stretched upwards until the liquid film is necked, the seal is broken to form bubbles, and the powder component is wrapped in the bubbles; (3) carrying out micro-fluid liquid drop separation on the hydrogel solution with the bubbles wrapping the solid powder to form hydrogel liquid drops wrapping the solid powder; (4) and crosslinking the hydrogel liquid drops wrapped with the solid powder to form solid powder-gel microspheres, namely P/H microspheres. The method directly encapsulates the powder in the bubble cavity, and can greatly improve the loading rate of the powder components.

Description

Preparation method of P/H microspheres wrapped with hydrophobic solid powder
Technical Field
The invention relates to the technical field of powder medicine/food packaging, in particular to a preparation method of P/H microspheres wrapping hydrophobic solid powder.
Background
Many hydrophobic pharmaceutical ingredients, nutrients or food bioactive substances exist in powder/solid form and are very important for human health. The powder components are widely applied to the pharmaceutical industry and food engineering, such as traditional Chinese medicine components with sterilizing and anti-inflammatory effects, such as camptothecin, resveratrol, quercetin and the like, which can be used for treating tumor and cancer, some water-insoluble vitamins, antioxidants and certain food coloring agents, particularly carotenoid and the like. However, these powder materials have poor stability, poor solubility and low bioavailability, and are very susceptible to external environmental forces such as light, oxygen, high temperature, humidity and the like during processing, storage and transportation, thereby greatly limiting the function of these poorly soluble powder components.
At present, the above problems can be solved by microencapsulation technology, in which active ingredients are packaged or embedded in a single or complex secondary material matrix to form submicron to hundreds of microns microspheres, thereby protecting the active ingredients. For the encapsulation of hydrophobic solid powder, the existing micro-encapsulation technology can be mainly divided into two major categories, namely a solvent dissolution method and a direct solid wrapping method. Solvent dissolution method the powder is dissolved in a suitable organic solvent to obtain a homogeneous solution, which is then dispersed in an emulsion, encapsulating the ingredients in a carrier such as granules, fibers, liposomes, and sponges. However, in view of the diversity of the various powder components, it is not easy to find an effective and compatible organic solvent. To solve this problem, direct solid encapsulation is to encapsulate the powder ingredients in a matrix such as a hydrogel or biopolymer, followed by spray drying, freeze drying or grinding to form particles. However, this method has a problem that the loading rate is not high, and the increase of the powder content in the solution changes the properties of the solution, for example, the viscosity of the solution shows an exponential increase, greatly increasing the packaging difficulty.
On the other hand, the choice of a suitable material for microencapsulation is critical to the encapsulation process and the subsequent release. Hydrogels are the best candidate due to their high water absorption, flexibility, biocompatibility, and biodegradability. In particular, the stimuli-responsive hydrogel has a wide application prospect in the field of intelligent drug release. However, difficulties are encountered in encapsulating hydrophobic powders due to the hydrophilic nature of hydrogels, resulting in complexity in material design, limiting their applicability.
There is therefore still much room for development in the encapsulation of hydrophobic solid powder ingredients for high loading, non-biotoxic encapsulation and controlled release.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a preparation method of P/H microspheres wrapping hydrophobic solid Powder, which improves the loading rate of the solid Powder and ensures that the formed Powder/gel microspheres (P/H microspheres) have mechanical stability and double Powder component release capacity.
The purpose of the invention is realized by the following technical scheme:
a preparation method of P/H microspheres wrapped with hydrophobic solid powder comprises the following steps:
s1: placing a hydrophobic solid powder on the surface of the hydrogel solution;
s2: immersing a frame for generating bubbles into the hydrogel solution with the surface provided with the solid powder, and then lifting the frame from the hydrogel solution, wherein a layer of hydrogel liquid film is attached to the frame; with the rising of the frame, the liquid film is continuously stretched upwards until the liquid film is necked, the seal is broken to form bubbles, and the powder component is wrapped in the bubbles;
s3: carrying out micro-fluid liquid drop separation on the hydrogel solution with the bubbles wrapping the solid powder to form hydrogel liquid drops wrapping the solid powder;
s4: and crosslinking the hydrogel liquid drops wrapped with the solid powder to form solid powder-gel microspheres, namely P/H microspheres.
Further, the microfluidic droplet separation is performed by:
injecting the hydrogel solution with the bubbles wrapping the solid powder into one channel of the microfluid T-shaped droplet generator, and forming hydrogel droplets wrapping the powder by utilizing the shearing action of the continuous phase relative to the hydrogel bubbles.
Furthermore, adding a surfactant into the hydrogel solution to reduce the interfacial tension of the solution, adding a high molecular weight polymer to prolong the existence time of a liquid film and bubbles, and adjusting the proportion of the hydrogel and the additive to obtain different bubble diameters.
Further, the flow rate of the continuous phase or the hydrogel solution is adjusted, the number of bubble cores in the P/H microspheres is changed, and a mononuclear, binuclear or polynuclear structure is formed.
Further, the ratio of the components in the hydrogel solution or the flow rate of the continuous phase or the flow rate of the hydrogel solution is adjusted, and the microsphere diameter, the minimum wall thickness and the average wall thickness of the P/H microspheres are changed.
Furthermore, the frames are arranged in multiple rows and multiple columns to form a frame network, each frame generates one bubble, and the frame network simultaneously generates a large number of bubbles to realize high-flux powder wrapping.
Further, in the case of the temperature-sensitive hydrogel, the temperature of the hydrogel solution should be maintained at 60 ℃ or higher in the processes of S1 to S3 to prevent the hydrogel solution from gelling.
Further, before the step S1, another substance is dissolved in the hydrogel solution, so that after the step S1-S4, the shell of the gel microsphere is loaded with the another substance, thereby obtaining the effect of dual loading.
Further, the hydrogel solution is prepared from agarose, Sodium Dodecyl Sulfate (SDS) and polyethylene oxide (PEO), wherein the concentration of the agarose is 2.5-4.5%.
The invention has the following beneficial effects:
(1) the method realizes powder wrapping through hydrogel bubbles, and avoids the use of organic solvents in the micro-packaging process.
(2) The method of the invention directly encapsulates the powder in the bubble cavity, which can greatly improve the loading rate of the powder components.
(3) The powder-gel microspheres formed by the method have a core-shell structure, have double carrying capacity, can perform double substance release and provide possibility for controllable programmed release of the medicine.
Drawings
FIG. 1 is a schematic diagram of a preparation method of P/H microspheres wrapped with hydrophobic solid powder according to the present invention; wherein, a represents the process of bubble formation, b represents the process of bubble separation and P/H microsphere formation;
FIG. 2 is a diagram of P/H microspheres, wherein the diameter of the microspheres is Dm, and the diameter of the bubbles is DbMinimum wall thickness dmin；
FIG. 3 is a side-by-side bubble frame structure provided in example 4;
FIG. 4 is a diagram of a P/H microsphere with different numbers of bubble cores, wherein a is a mononuclear structure, b is a binuclear structure, and c is a trinuclear structure;
FIG. 5 is a graph showing the control of the ratio of hydrogel solution to bubble size;
FIG. 6 is the flow rate of the continuous phase and the ratio of the hydrogel solution to the size of the microspheres;
FIG. 7 shows the mechanical property test results of the P/H microsphere provided by the present invention, wherein, a and b are respectively the stress-strain curve and the burst pressure of the P/H microsphere containing agarose of different concentrations, and c and d are respectively the stress-strain curve and the burst pressure of the P/H microsphere of different wall thickness;
FIG. 8 is a schematic diagram of the P/H microsphere drug release principle provided by the present invention;
FIG. 9 is a graph of the release of the P/H microspheres of the drug provided in example 1, wherein the left side of the graph a is before release of ultrasound and the right side is after release of ultrasound; b is a graph of the cumulative release of the drug over time.
In the figure: 1 is solid powder, 2 is hydrogel solution, 3 is a frame, 4 is a hydrogel liquid film, 5 is a hydrogel bubble for loading powder, 6 is a T-shaped droplet generator, 7 is hydrogel droplets, 8 is powder-gel microspheres (P/H microspheres), and 9 is a collecting tank.
Detailed Description
The present invention will be described in detail below with reference to the accompanying drawings and preferred embodiments, and the objects and effects of the present invention will become more apparent, it being understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.
The invention discloses a preparation method of P/H microspheres wrapped with hydrophobic solid Powder, which comprises the steps of generating hydrogel bubbles to wrap the Powder, then shearing the hydrogel bubbles by a microfluidic droplet generation device to form hydrogel droplets wrapped with the Powder, and finally forming Powder-gel microspheres (P/H microspheres) of a core-shell structure wrapped with the Powder by hydrogel crosslinking.
Preparing a hydrogel solution (such as agarose, gelatin, etc.) with a certain concentration, and adding a surfactant or an additive.
As shown in fig. 1, the powder component is placed on the surface of the hydrogel solution, and the frame for generating bubbles is immersed in the hydrogel solution with the powder component on the surface. The interfacial tension due to the hydrophobicity of the powder is balanced with the gravity of the powder, so that the powder stays on the surface without sinking. The frame is then lifted from the hydrogel solution, whereupon a thin film of hydrogel is attached to the frame. And with the rising of the frame, the liquid film is continuously stretched upwards until the liquid film is necked, and finally, the seal is broken due to the instability of the Rayleigh platform to form bubbles, so that the powder components are wrapped in the bubbles. Due to the Pickering effect, a portion of the powder also acts as a surfactant, which promotes the formation of gas bubbles and stabilizes them.
And injecting the generated hydrogel bubbles wrapped with the powder into a channel of the microfluidic droplet generation device, and shearing the hydrogel bubbles by utilizing continuous phase to form hydrogel droplets wrapped with the powder.
Then the hydrogel liquid drop wrapped with the powder is converted into solid P/H microspheres after cross-linking (cooling, illumination and the like). Due to the buoyancy effect generated by the bubbles in the P/H microspheres, the P/H microspheres are of an eccentric structure. The resulting microspheres had a diameter Dm, bubble diameter Db, minimum wall thickness dmin, and average wall thickness d. A physical diagram of the P/H microsphere is shown in FIG. 2.
Different bubble diameters can be obtained by adjusting the proportion of each component in the hydrogel solution.
The flow rate of the continuous phase or the hydrogel solution is adjusted, so that the number of bubble cores in the P/H microspheres can be changed, and a mononuclear, binuclear or polynuclear structure is formed.
The microsphere diameter, the minimum wall thickness and the average wall thickness of the P/H microspheres can be changed by adjusting the proportion of each component in the hydrogel solution or the flow rate of the continuous phase or the flow rate of the hydrogel solution.
In order to realize large flux powder wrapping, the frames for generating bubbles are arranged side by side to form a frame network, and a large amount of bubble wrapping powder can be generated at the same time.
The preparation method of the P/H microspheres can also realize the effect of double carrying, and at the moment, another substance needs to be dissolved in the hydrogel solution firstly, and then the other substance is loaded in the shells of the finally obtained P/H microspheres after the steps are carried out.
The produced P/H microspheres have excellent mechanical properties and can bear certain external load, so that the internal wrapping substances are protected from being interfered by the outside, and the stability of the P/H microspheres is improved. The agarose concentration and the minimum wall thickness have great influence on the mechanical properties of the P/H microspheres.
Example 1
And preparing a hydrogel solution. 3% agarose, 0.2% Sodium Dodecyl Sulfate (SDS) and 0.01% polyethylene oxide (PEO, M) were usedW4M g/mol). Agarose as the hydrogel matrix material, SDS as the surfactant, PEO was used mainly to improve bubble stability. The three powders are stirred uniformly in deionized water, heated in a microwave oven until the solution is transparent, and then ultrasonically degassed for 30 seconds. Nanometer calcium carbonate powder is used as a drug model in the air bubbles. Calcium carbonate powder was placed on the surface of the hydrogel solution. Immersing the frame for generating the air bubbles into the hydrogel solution with calcium carbonate powder on the surface, and then lifting the frame from the hydrogel solution to wrap the powder components inside the air bubbles. In this process, it is necessary to keep the hydrogel solution above 60 ℃ to prevent it from gelling.
As shown in FIG. 1b, the hydrogel bubble solution is injected into the T-shaped droplet generator, the hydrogel channel part of the T-shaped droplet generator is provided with a heating device, the temperature of the heating jacket is kept above 60 ℃, 50cSt silicone oil is selected as a continuous phase, the flow rate of the silicone oil is adjusted to 120ml/h, and the flow rate of the hydrogel is adjusted to 20 ml/h. The hydrogel bubble solution forms hydrogel droplets under the shearing action of the silicone oil. Then the hydrogel liquid drop is cooled in a silicone oil environment under a room temperature environment to be converted into solid P/H microspheres. The characteristic parameters of the prepared P/H microspheres are shown in Table 1.
TABLE 1 characteristic parameters of P/H microspheres obtained in example 1
Diameter of microsphere Dm/μm Diameter D of the bubbleb/μm Minimum wall thickness dmin/μm Average wall thickness d/mum
1780 1060 150 295
Example 2
And preparing a hydrogel solution. The hydrogel solution was prepared from 12% gelatin, 0.2% SDS and 0.1% PEO. Nanometer calcium carbonate powder is used as a drug model in the air bubbles. Gelatin is used as a hydrogel base material, SDS is used as a surfactant, and PEO is mainly used for improving the bubble stability. The three powders are stirred uniformly in deionized water, heated in a microwave oven until the solution is transparent, and then ultrasonically degassed for 30 seconds. Nanometer calcium carbonate powder is used as a drug model in the air bubbles. Calcium carbonate powder was placed on the surface of the hydrogel solution. Immersing the frame for generating the air bubbles into the hydrogel solution with calcium carbonate powder on the surface, and then lifting the frame from the hydrogel solution to wrap the powder components inside the air bubbles. In this process, it is necessary to keep the hydrogel solution above 60 ℃ to prevent it from gelling.
Injecting the hydrogel bubble solution into a T-shaped droplet generator, arranging a heating device at a hydrogel channel part of the T-shaped droplet generator, keeping the temperature of a heating sleeve above 60 ℃, selecting 50cSt silicone oil as a continuous phase, and adjusting the flow rate of the silicone oil to 100ml/h and the flow rate of the hydrogel to 25 ml/h. The hydrogel bubble solution forms hydrogel droplets under the shearing action of the silicone oil. Then the hydrogel liquid drop is cooled in a silicone oil environment under a room temperature environment to be converted into solid P/H microspheres. The characteristic parameters of the prepared P/H microspheres are shown in Table 2.
TABLE 2 characteristic parameters of P/H microspheres obtained in example 2
Diameter of microsphere Dm/μm Diameter D of the bubbleb/μm Minimum wall thickness dmin/μm Average wall thickness d/mum
2000 1140 150 330
Example 3
And preparing a hydrogel solution. 3% sodium alginate, 0.2% SDS and 0.1% PEO are selected to prepare the hydrogel solution. Nanometer calcium carbonate powder is used as a drug model in the air bubbles. Sodium alginate is used as a hydrogel substrate material, SDS is used as a surfactant, and PEO is mainly used for improving the stability of bubbles. The three powders are stirred uniformly in deionized water, heated in a microwave oven until the solution is transparent, and then ultrasonically degassed for 30 seconds. Nanometer calcium carbonate powder is used as a drug model in the air bubbles. Calcium carbonate powder was placed on the surface of the hydrogel solution. Immersing the frame for generating the air bubbles into the hydrogel solution with calcium carbonate powder on the surface, and then lifting the frame from the hydrogel solution to wrap the powder components inside the air bubbles.
Injecting the hydrogel bubble solution into a T-shaped droplet generator, selecting a 10% calcium chloride solution as a continuous phase, and adjusting the flow rate of the calcium chloride solution to 80ml/h and the flow rate of the hydrogel to 20 ml/h. The hydrogel bubble solution forms hydrogel droplets under the shearing action of the calcium chloride solution, and then the hydrogel droplets are crosslinked into solid P/H microspheres. The characteristic parameters of the prepared P/H microspheres are shown in Table 3.
TABLE 3 characteristic parameters of P/H microspheres obtained in example 3
Diameter of microsphere Dm/μm Diameter D of the bubbleb/μm Minimum wall thickness dmin/μm Average wall thickness d/mum
1850 1100 90 325
Example 4
And preparing a hydrogel solution. 3% agarose, 0.2% SDS and 0.01% PEO were selected. Agarose as the hydrogel matrix material, SDS as the surfactant, PEO was used mainly to improve bubble stability. After the three powders are uniformly stirred in deionized water, the three powders are heated in a microwave oven until the solution is transparent, and then the three powders are degassed by ultrasound for 30 seconds. Nanometer calcium carbonate powder is used as a drug model in the air bubbles. Calcium carbonate powder was placed on the surface of the hydrogel solution. In order to realize large flux powder wrapping, the frames for generating bubbles are arranged side by side to form a frame network, and a large amount of bubble wrapping powder can be generated at the same time. The framework network is shown in fig. 3.
The preparation method of the P/H microspheres provided by the invention can also obtain the P/H microspheres with different shapes and sizes by adjusting the operation parameters or the solution ratio, and is proved by the following experiments.
The core number of bubbles in the P/H microspheres can be changed by controlling the flow rate of a continuous phase or a hydrogel solution in the T-shaped droplet generator, so that the P/H microspheres with different core numbers are obtained, multi-core wrapping is realized, and the P/H microspheres have the capacity of loading different powder components. In example 1, P/H microspheres having mononuclear, dinuclear and trinuclear structures were formed by adjusting the flow rates of the hydrogel to 18ml/H, 54ml/H and 80ml/H, respectively, as shown in FIG. 4.
The bubble diameter D of the P/H microspheres can be changed by controlling the proportion of the hydrogel solution (agarose concentration, SDS concentration or PEO concentration)bThe effect of the various parameters on bubble size is shown in fig. 5.
The microsphere diameter D of the P/H microspheres can be changed by controlling the flow rate of the continuous phase (silicon oil) in the T-shaped droplet generator and the proportion of the hydrogel solution (agarose concentration, SDS concentration or PEO concentration)mMinimum wall thickness dminAnd averaging the wall thickness d to obtain P/H microspheres with different sizes, and the influence of each parameter on the size of the microspheres is shown in fig. 6.
The P/H microsphere prepared by the invention has excellent mechanical property and can bear certain external load, thereby protecting the internal wrapping substance. The agarose concentration has a great influence on the mechanical properties of the hydrogel. Against agarose, SDS and PEO (M)W4M g/mol)) was prepared, the agarose concentration was varied between 2.5% and 4.5%, and the resulting P/H microspheres were subjected to a mechanical compression test. FIG. 7a shows typical compressive stress-strain curves for P/H microspheres at different agarose concentrations. As the agarose concentration increased between 2.5% and 4.5%, the compressive stress of the P/H microspheres increased from 0.015MPa to 0.12MPa, and FIG. 7b shows that the burst pressure increased from 35mN to 300mN, indicating that a dense network was formed in the hydrogel. When the solution ratio is determined, the minimum wall thickness of the P/H microspheres has a decisive influence on the mechanical strength, since this location is the weak point of the P/H microspheres. Mechanical compression testing was performed on P/H microspheres of different wall thicknesses, and FIG. 7c shows the smallest wallInfluence of thickness on mechanical properties of the P/H microspheres. When the minimum wall thickness was increased from 50 μm to 250 μm, the compressive stress of the P/H microspheres increased from 0.029MPa to 0.10MPa, and FIG. 7d shows that the burst pressure increased from 67mN to 223 mN.
The P/H microsphere prepared by the method has a core-shell structure, can be loaded with different powder components, and has dual-release capacity. As an embodiment thereof, the release diagram is shown in fig. 8. The external hydrogel shell releases the powder component 1 in a 37 ℃ water phase environment, the hydrogel is continuously cracked into fragments under the action of ultrasound, the powder component 2 wrapped by the internal bubbles is released, and the programmable controlled release characteristic is presented according to the ultrasound action time, intensity and frequency.
In order to show the dual drug loading and controllable release performance of the P/H microspheres, a drug release experiment was performed. In example 1, rhodamine B was dissolved in the hydrogel solution during the preparation of the hydrogel solution as a small molecule release model in the microsphere shell. The other operations were the same as in example 1. Thus obtaining the P/H microspheres loaded with rhodamine B in the hydrogel shell and loaded with nano calcium carbonate powder in the hydrogel bubbles. The prepared P/H microspheres are placed in water at 37 ℃ to test the release of rhodamine B. The P/H microspheres were placed in an ultrasonic environment and tested for calcium carbonate release. The release result is shown in fig. 9, rhodamine loaded in the hydrogel shell has the characteristic of slow release after explosive release over time, and calcium carbonate powder wrapped in the bubbles has the characteristic of controllable stepped release under the action of ultrasound.
It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and although the invention has been described in detail with reference to the foregoing examples, it will be apparent to those skilled in the art that various changes in the form and details of the embodiments may be made and equivalents may be substituted for elements thereof. All modifications, equivalents and the like which come within the spirit and principle of the invention are intended to be included within the scope of the invention.

Claims (9)

1. A preparation method of P/H microspheres wrapped with hydrophobic solid powder is characterized by comprising the following steps:
s1: placing a hydrophobic solid powder on the surface of the hydrogel solution;
s2: immersing a frame for generating bubbles into the hydrogel solution with the surface provided with the solid powder, and then lifting the frame from the hydrogel solution, wherein a layer of hydrogel liquid film is attached to the frame; with the rising of the frame, the liquid film is continuously stretched upwards until the liquid film is necked, the seal is broken to form bubbles, and the powder component is wrapped in the bubbles;
s3: injecting the hydrogel solution with the bubbles wrapping the solid powder into a channel of the microfluidic droplet generation device, and shearing the hydrogel bubbles by utilizing continuous phase to form hydrogel droplets wrapping the solid powder;
s4: and crosslinking the hydrogel liquid drops wrapped with the solid powder to form solid powder-gel microspheres, namely P/H microspheres.
2. The method for preparing hydrophobic solid powder-coated P/H microspheres according to claim 1, wherein the step S3 is performed by:
injecting the hydrogel solution with the bubbles wrapping the solid powder into one channel of the microfluid T-shaped droplet generator, and forming hydrogel droplets wrapping the powder by utilizing the shearing action of the continuous phase relative to the hydrogel bubbles.
3. The method of claim 1, wherein the surfactant is added to the hydrogel solution to reduce interfacial tension of the solution, the polymer with high molecular weight is added to prolong the existence time of the liquid film and the bubbles, and the ratio of the hydrogel to the additive is adjusted to obtain different diameters of the bubbles.
4. The method for preparing P/H microspheres coated with hydrophobic solid powder according to claim 2, wherein the flow rate of the continuous phase or the hydrogel solution is adjusted to change the number of bubble cores inside the P/H microspheres to form a mononuclear, binuclear or polynuclear structure.
5. The method for preparing hydrophobic solid powder-coated P/H microspheres according to claim 2, wherein the ratio of the components in the hydrogel solution or the flow rate of the continuous phase or the flow rate of the hydrogel solution is adjusted to change the microsphere diameter, the minimum wall thickness and the average wall thickness of the P/H microspheres.
6. The method for preparing hydrophobic solid powder-coated P/H microspheres according to claim 1, wherein the frames are arranged in a plurality of rows and columns to form a frame network, each frame generates one bubble, and the frame network simultaneously generates a large number of bubbles to realize high-flux powder coating.
7. The method for preparing hydrophobic solid powder-coated P/H microspheres according to claim 1, wherein for the temperature-sensitive hydrogel, the temperature is maintained at 60 ℃ or higher during the S1-S3 process to prevent the hydrogel solution from gelling.
8. The method for preparing hydrophobic solid powder-coated P/H microspheres according to claim 1, wherein before S1, another substance is dissolved in the hydrogel solution, so that after S1-S4, the shell of the gel microspheres is loaded with the another substance, thereby obtaining the effect of dual loading.
9. The method for preparing hydrophobic solid powder-coated P/H microspheres according to claim 1, wherein the hydrogel solution is prepared from agarose, sodium dodecyl sulfate and polyethylene oxide, wherein the concentration of the agarose is 2.5% -4.5%.
CN202011471957.6A 2020-12-14 2020-12-14 Preparation method of P/H microspheres wrapped with hydrophobic solid powder Active CN112618517B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011471957.6A CN112618517B (en) 2020-12-14 2020-12-14 Preparation method of P/H microspheres wrapped with hydrophobic solid powder

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011471957.6A CN112618517B (en) 2020-12-14 2020-12-14 Preparation method of P/H microspheres wrapped with hydrophobic solid powder

Publications (2)

Publication Number Publication Date
CN112618517A CN112618517A (en) 2021-04-09
CN112618517B true CN112618517B (en) 2021-10-22

Family

ID=75312848

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011471957.6A Active CN112618517B (en) 2020-12-14 2020-12-14 Preparation method of P/H microspheres wrapped with hydrophobic solid powder

Country Status (1)

Country Link
CN (1) CN112618517B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113893792B (en) * 2021-11-10 2024-02-02 内蒙古科技大学 High-strength SiO with special wettability 2 Base composite aerogel microspheres
CN113976051B (en) * 2021-11-15 2022-08-23 国科温州研究院(温州生物材料与工程研究所) From showy aquogel preparation facilities based on micro-fluidic
CN114376984B (en) * 2022-01-17 2022-10-21 浙江大学 Preparation method of self-floating MP/H microspheres wrapped with water-insoluble solid powder
CN114452906A (en) * 2022-01-25 2022-05-10 南方科技大学 Method for preparing foam hydrogel

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6562361B2 (en) * 2001-05-02 2003-05-13 3M Innovative Properties Company Pheromone immobilized in stable hydrogel microbeads
CN106582429B (en) * 2016-10-28 2018-08-14 浙江大学 Hydrophobic Janus particles of hydrogel-and preparation method thereof
CN106619488A (en) * 2016-11-29 2017-05-10 广州新诚生物科技有限公司 Preparation method and application of microsphere-loaded PHEMA hydrogel drug carrying body
CN106987012B (en) * 2017-03-30 2019-06-18 华南理工大学 A kind of Janus microballoon-hydrogel second level motor and preparation method thereof of bubble driving
CN111253593B (en) * 2020-03-13 2023-03-03 段忆翔 Method for assembling periodic nano structure on plane or curved surface by using soft matter interface

Also Published As

Publication number Publication date
CN112618517A (en) 2021-04-09

Similar Documents

Publication Publication Date Title
CN112618517B (en) Preparation method of P/H microspheres wrapped with hydrophobic solid powder
Zhao Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery
Yow et al. Formation of liquid core–polymer shell microcapsules
US6495161B1 (en) Cytoprotective biocompatible containment systems for biologically active materials and methods of making same
JP4704039B2 (en) Porous beads and method for producing the same
Seiffert Functional microgels tailored by droplet‐based microfluidics
JP7082358B2 (en) How to make capsules made of a cross-linked hydrogel shell that surrounds the central core
JP2014529625A (en) System and method for shell encapsulation
Mark et al. Manufacture of chitosan microbeads using centrifugally driven flow of gel-forming solutions through a polymeric micronozzle
Ge et al. Layer-by-layer self-assembly of giant polyelectrolyte microcapsules templated by microbubbles as potential hydrophilic or hydrophobic drug delivery system
Huang et al. Engineering microcapsules for simultaneous delivery of combinational therapeutics
Huang et al. Fabrication of multicore milli-and microcapsules for controlling hydrophobic drugs release using a facile approach
WO2021258668A1 (en) Method for preparing p/h microspheres with hydrophobic solid powder wrapped therein
US20230415116A1 (en) Encased Oil Core Microcapsules
Chen et al. Porous ultrathin-shell microcapsules designed by microfluidics for selective permeation and stimuli-triggered release
CN109078195B (en) Thermosensitive drug-loaded micro-organic gel with shell layer containing graphene quantum dots and core containing magnetic nanoparticles, and preparation method and application thereof
Ju et al. Lab-on-a-chip fabrication of polymeric microparticles for drug encapsulation and controlled release
Vergaro et al. TGF-beta inihibitor-loaded polyelectrolyte multilayers capsules for sustained targeting of hepatocarcinoma cells
Kudryavtseva et al. Printed asymmetric microcapsules: Facile loading and multiple stimuli-responsiveness
Su et al. Fabrication of monodisperse droplets and microcapsules using microfluidic chips: a review of methodologies and applications
CN102489230A (en) Preparation method of biodegradable polymer microcapsules
Gahan et al. Polymer Coatings Comprised Entirely of Soft and Semipermeable Microcapsules
CN114376984B (en) Preparation method of self-floating MP/H microspheres wrapped with water-insoluble solid powder
US20240123417A1 (en) Capsules With a Hydrogel Matrix
JP7134489B2 (en) Method for producing microcapsules or beads

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant