CN113679847B - Magnetic controlled release carrier based on emulsion system and preparation method thereof - Google Patents
Magnetic controlled release carrier based on emulsion system and preparation method thereof Download PDFInfo
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- CN113679847B CN113679847B CN202110155177.9A CN202110155177A CN113679847B CN 113679847 B CN113679847 B CN 113679847B CN 202110155177 A CN202110155177 A CN 202110155177A CN 113679847 B CN113679847 B CN 113679847B
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- 238000013270 controlled release Methods 0.000 title claims abstract description 59
- 239000000839 emulsion Substances 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000006249 magnetic particle Substances 0.000 claims abstract description 79
- 239000004519 grease Substances 0.000 claims abstract description 36
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 27
- RPWFJAMTCNSJKK-UHFFFAOYSA-N Dodecyl gallate Chemical compound CCCCCCCCCCCCOC(=O)C1=CC(O)=C(O)C(O)=C1 RPWFJAMTCNSJKK-UHFFFAOYSA-N 0.000 claims abstract description 24
- 235000010386 dodecyl gallate Nutrition 0.000 claims abstract description 23
- 239000004480 active ingredient Substances 0.000 claims abstract description 21
- 230000008569 process Effects 0.000 claims abstract description 21
- 238000002844 melting Methods 0.000 claims abstract description 19
- 230000008018 melting Effects 0.000 claims abstract description 19
- 238000001816 cooling Methods 0.000 claims abstract description 15
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000725 suspension Substances 0.000 claims description 30
- 229940110456 cocoa butter Drugs 0.000 claims description 25
- 235000019868 cocoa butter Nutrition 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical group CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 17
- 239000007864 aqueous solution Substances 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 8
- 238000001132 ultrasonic dispersion Methods 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000000084 colloidal system Substances 0.000 claims description 4
- 150000002632 lipids Chemical class 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 8
- 238000005286 illumination Methods 0.000 abstract description 8
- 239000007787 solid Substances 0.000 abstract description 6
- 230000008685 targeting Effects 0.000 abstract description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 32
- 229940109262 curcumin Drugs 0.000 description 16
- 235000012754 curcumin Nutrition 0.000 description 16
- 239000004148 curcumin Substances 0.000 description 16
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- 239000002122 magnetic nanoparticle Substances 0.000 description 7
- 238000000265 homogenisation Methods 0.000 description 6
- 239000002245 particle Substances 0.000 description 5
- 239000007790 solid phase Substances 0.000 description 5
- 235000019197 fats Nutrition 0.000 description 4
- 229960004887 ferric hydroxide Drugs 0.000 description 4
- 238000002073 fluorescence micrograph Methods 0.000 description 4
- IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000010276 construction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 235000011837 pasties Nutrition 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000007711 solidification Methods 0.000 description 3
- 230000008023 solidification Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 239000007908 nanoemulsion Substances 0.000 description 2
- 229940031182 nanoparticles iron oxide Drugs 0.000 description 2
- 230000010355 oscillation Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N trilaurin Chemical compound CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000001218 confocal laser scanning microscopy Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- -1 lauroyl ester Chemical class 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002114 nanocomposite Substances 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 238000006479 redox reaction Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
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- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
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- Inorganic Chemistry (AREA)
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- General Preparation And Processing Of Foods (AREA)
Abstract
The invention provides a magnetic controlled release carrier based on an emulsion system, and a preparation method and application thereof. The preparation method comprises the following steps: in an emulsion system, the melted grease is combined with the magnetic particles, and the solid lipid balls with the surfaces embedded with the magnetic particles are formed by cooling, namely the magnetic controlled release carrier; wherein the magnetic particles are ferroferric oxide magnetic particles with the surfaces modified by lauryl gallate. The magnetic controlled release carrier can accurately adjust the illumination area and the illumination intensity on the basis of having magnetic targeting potential, effectively control the melting state of the carrier body and release active ingredients, and simultaneously, the effect of the emulsifying agent can maintain the stable state of the magnetic controlled release carrier in the release process.
Description
Technical Field
The invention belongs to the technical field of food and drug processing, and particularly relates to a magnetic controlled release carrier based on an emulsion system and a preparation method thereof.
Background
The nanoemulsion can be used as a delivery system of lipophilic compounds with biological activity and used in the processing and storage processes of food and medicine fields, and research shows that the nanoemulsion has more excellent performance than common emulsions, and can prevent the degradation of active ingredients in foods, thereby improving the bioavailability. In recent years, nanocomposite structures with drug loading and superparamagnetic functions have received a great deal of attention in the biomedical field. With the discovery and application of various functional ingredients, many active ingredients are generally faced with: poor water solubility, poor stability, etc. Therefore, the construction of the carrier capable of improving the availability of the active ingredient has important significance.
Magnetic iron oxide nanoparticles are receiving great attention for their excellent magnetic properties, biocompatibility and potentially non-toxic properties. It can be manipulated and controlled by external magnetic fields, an additional important material, has been used in many fields including biology, pharmacy and diagnostics. Furthermore, iron is a nutrient that can be metabolized by cellular regulation via the transferrin pathway. In recent years, research on near infrared photothermal effect of magnetic iron oxide nanoparticles has been conducted, and it has been found that it has good photothermal conversion efficiency.
Disclosure of Invention
The invention provides a magnetic controlled release carrier based on an emulsion system and a preparation method thereof, which can control release efficiency by controlling illumination intensity and area by utilizing the excellent photo-thermal conversion performance of magnetic particles and has simple and convenient operation.
A method for preparing a magnetic controlled release carrier based on an emulsion system, comprising the following steps:
in an emulsion system, the melted grease is combined with the magnetic particles, and solid lipid balls with the surfaces embedded with the magnetic particles are formed by cooling, namely the magnetic controlled release carrier;
wherein the magnetic particles are ferroferric oxide (Fe) with surface modified by lauryl gallate 3 O 4 ) Magnetic particles.
In the magnetic controlled release carrier, the magnetic particles have the function of photo-thermal conversion; in the controlled release process, the magnetic particles can raise the temperature of the attached solid grease balls to the melting point through photo-thermal conversion, and the solid grease balls are converted into a molten state from a solid phase, and the fat-soluble active ingredients loaded in the grease balls overflow due to the instability of a system in which the fat-soluble active ingredients are positioned.
Preferably, a method for preparing a magnetic controlled release carrier based on an emulsion system comprises the following steps:
mixing the magnetic particle suspension, the melted grease and the emulsifying agent, homogenizing, and cooling to obtain the magnetic controlled release carrier.
Preferably, the magnetic particle suspension is preheated prior to mixing with the melted fat and emulsifier to ensure that the fat is always in a melted state.
Preferably, the magnetic particles whose surface is modified with lauryl gallate are made of ferric hydroxide (Fe (OH) 3 ) Colloidal solution and no foodThe lauroyl ester is prepared by oxidation-reduction reaction.
The preparation method comprises mixing lauryl gallate aqueous solution with Fe (OH) 3 Mixing the colloid solutions, adding into a high-pressure heating kettle, heating at 150-250deg.C for 1-6 hr (such as 200 deg.C for 3 hr), and reducing with hydroxy of lauryl gallate to obtain (Fe) modified with lauryl gallate 3 O 4 ) And (5) carrying out post-treatment on the system liquid of the magnetic nano particles to obtain the magnetic particles.
Preferably, the concentration of ferric hydroxide in the ferric hydroxide colloidal solution is 0.03-0.08 mol/L. The concentration of the lauryl gallate aqueous solution is 0.01-0.05 mol/L. The molar ratio of the lauryl gallate to the ferric hydroxide is (0.1-0.8): 1.
as a further preferred aspect, the magnetic particle suspension is prepared by:
and dissolving the magnetic particles in water, and performing ultrasonic dispersion to obtain the magnetic particle suspension.
Wherein the power of ultrasonic dispersion is preferably 400-800W, and the dispersion time is preferably 10-30 s; the power of ultrasonic dispersion is more preferably 800W, and the dispersion time is more preferably 10s. The mass volume ratio of the magnetic particles to the water in the magnetic particle suspension is 0.8-1.5 mg/mL.
More preferably, in the homogenizing, the homogenizing speed is 12000-16000 rpm, and the homogenizing time is 1-5 min. The homogenization speed is more preferably 14000rpm, and the homogenization time is more preferably 3min.
As a further preference, the emulsifier is tween-80 or span-60; still more preferably span-60, which has a melting point in the range of 49-52 ℃.
As a further preferred aspect, the mass to volume ratio of the emulsifier to water (referring to the water in the magnetic particle suspension) is preferably 18 to 50mg/mL; further preferably 20 to 50mg/mL; further preferably 24 to 48mg/mL.
Preferably, the oil is one of glycerol trilaurate, glycerol tristearate and cocoa butter; further preferred is cocoa butter having a melting point in the range of 34 to 38 ℃. The cocoa butter is used as the widely applied natural edible oil, and the safety and the economy are favorable for further popularization.
Preferably, the melting point of the fat is lower than the melting point of the emulsifier. In the invention, the oil phase of the emulsion system is cocoa butter, the melting point range is 34-38 ℃, and the melting point range of span-60 is 49-52 ℃, so that the span-60 is in a solidification state earlier than the oil phase in the process of cooling after the construction of the emulsion system is completed because the melting point of the emulsifying agent span-60 is slightly higher than that of the cocoa butter, the emulsion system cooled at room temperature can be stabilized, emulsion stability can be effectively maintained, and the solid-phase magnetic lipid ball carrier is obtained. In the photo-thermal controlled release process, the difference of the melting points can be utilized to achieve the effect of controlled release. The emulsifier is span-60, and the grease is the combination of cocoa butter, so that the stability of the controlled release process can be further ensured.
Then forming lipid spheres with magnetic particles embedded on the surfaces by utilizing the affinity of the lauryl gallate coated on the surfaces of the magnetic nanoparticles and the grease in a molten state in an aqueous solution; meanwhile, due to the characteristic that the added emulsifier has a slightly higher melting point than grease, the emulsion system cooled at room temperature can be stabilized, and the solid-phase magnetic lipid ball carrier is obtained. The method synthesizes modified magnetic particles in one step, constructs a stable emulsion system, synthesizes a magnetic carrier, and can be used for further active ingredient carrying research.
According to the invention, after the emulsion system is constructed, in the cooling process, the emulsifier is advanced to a solidification state in advance than the grease, so that the emulsion stability can be effectively maintained; in the photo-thermal controlled release process, the effect of controlling release can be achieved by utilizing the difference of the melting points.
Preferably, in the emulsion system, the concentration of the magnetic particles is 0.3-1.6 mg/mL; further preferably 0.3 to 1.3mg/mL; still more preferably 0.3 to 1mg/mL.
Preferably, in the emulsion system, the volume ratio of the melted grease to the water is 1: (4-6); further preferably 1:5.
the invention mainly relates to three aspects, namely (1) preparing a magnetic nanoparticle solution with the surface modified by lauryl gallate; (2) Screening grease and a surfactant (or an emulsifying agent) of the emulsion system; (3) The oil-water ratio of the emulsion system and the addition amount of the magnetic particles are screened.
As a specific preference, a method for preparing a magnetic controlled release carrier based on an emulsion system comprises the following steps:
(1) Dissolving magnetic particles in water, and performing ultrasonic dispersion for 10-30 s under 400-800W power to prepare uniform magnetic particle suspension;
(2) Preheating the magnetic particle suspension, mixing with melted grease and an emulsifying agent, homogenizing for 1-5 min at 12000-16000 rpm, and cooling in an ice bath to obtain the magnetic controlled release carrier.
The solid lipid in the carrier has a nutrition function, and the magnetic controlled release carrier can be used as a controlled release raw material of grease; moreover, the magnetic controlled release carrier has light control performance, so that noninvasive grease release control can be realized in some medical occasions.
Preferably, the active ingredient to be loaded is optionally added during the preparation process, specifically as follows:
(1) Dissolving magnetic particles in water, and performing ultrasonic dispersion for 10-30 s under 400-800W power to prepare uniform magnetic particle suspension;
(2) And (3) preheating the magnetic particle suspension, mixing the preheated magnetic particle suspension with melted grease, active ingredients to be loaded and an emulsifying agent, homogenizing for 1-5 min at 12000-16000 rpm, and cooling in an ice bath to obtain the magnetic controlled release carrier loaded with the active ingredients.
Of course, the embedding of the active ingredient may also be carried out using the prepared carrier. Generally comprises: homogenizing the melted magnetic controlled release carrier and active components at 12000-16000 rpm for 1-5 min, and cooling in ice bath to obtain the magnetic controlled release carrier loaded with active components.
The invention utilizes the affinity effect of the lauryl gallate coated on the surfaces of the magnetic particles and the melted grease in the aqueous solution to form the lipid ball with the magnetic particles embedded on the surfaces; the emulsifier can stabilize the emulsion system in the cooling process, so that the grease balls can independently exist in microsphere form, and the solid-phase magnetic grease ball carrier is obtained.
The carrier system of the invention contains Fe 3 O 4 Lipid globules of magnetic particles, fe 3 O 4 The surface of the magnetic particles is modified by lauryl gallate, and the emulsion system is stabilized by an emulsifying agent in the emulsion system to synthesize a carrier capable of carrying active ingredients.
The span-60 is used as an emulsifying agent to synthesize a novel carrier capable of carrying active ingredients, which comprises the following specific steps:
(1) Utilizing the affinity of lauryl gallate coated on the surfaces of magnetic nano particles and cocoa butter in a molten state in an aqueous solution to form lipid spheres embedded with the magnetic particles;
(2) The emulsion system of span-60 in the stable cooling process can be used for obtaining the magnetic lipid ball carrier.
A magnetic controlled release carrier based on an emulsion system is prepared by the preparation method according to any one of the technical schemes.
In the invention, the emulsifier mainly plays a role in stabilizing and controlling release, and in the process of forming the grease balls, after homogenizing operation, the emulsifier is solidified, so as to provide a stable cooling environment for the grease balls, ensure that the grease balls exist in the form of single solid balls and avoid aggregation and solidification of oil phases. The finally formed lipid sphere with magnetic particles embedded on the surface is stabilized as a whole by an emulsifier. The magnetic particles have the function of realizing photo-thermal conversion, so that the lipid (namely the cocoa butter) inlaid in the magnetic particles is heated to the melting point of the lipid, the lipid is converted into a molten state from a solid phase, and the active ingredient (such as curcumin) loaded in the lipid overflows due to the instability of a system in which the active ingredient is positioned, so that the controllable release of the active ingredient is realized.
In theory, in a sufficiently homogeneous process, the particles inside collide with each other, and the surface of the magnetic nanoparticle is hydrophobic chains linked to lauryl gallate, so that there are two tendencies of the particles in the aqueous solution, one to find the same hydrophobic chain as it is, and one to bind to the grease. From the results, the finally formed grease ball embedded with magnetic nano particles has not only monodisperse magnetic particles on the surface, but also a plurality of magnetic particles embedded on the surface together, and the latter is formed by the impact of homogeneous waves after the grease ball is impacted with the grease after the grease ball is aggregated under the action of an emulsifying agent. The possibility of the emulsifier binding to the particles and the fat, respectively, is much reduced under the influence of the homogenization step. In the screening process, the choice of homogenization rate is also critical, considering the presence or absence of individual magnetic nanoparticles.
The magnetic controlled release carrier can accurately adjust the illumination area and the illumination intensity on the basis of having magnetic targeting potential, effectively control the melting state of the carrier body and release active ingredients, and simultaneously, the effect of the emulsifying agent can maintain the stable state of the magnetic controlled release carrier in the release process.
Compared with the prior art, the invention has the beneficial effects that:
(1) The magnetic controlled release carrier has better magnetic response and photo-thermal performance and high controllability, can control release efficiency by adjusting illumination intensity and illumination area, and is simple and convenient to operate.
(2) The lauryl gallate and the grease have the advantages of wide raw material sources, low price and simple and convenient manufacturing process, and are suitable for industrial production and application.
Drawings
FIG. 1 is a micrograph of the emulsion system prepared in example 1 of the present invention after dilution;
FIG. 2 is a scanning electron microscope image of the emulsion system prepared in example 1 of the present invention after dilution;
FIG. 3 is a line-scan spectrum analysis chart of the magnetic controlled release carrier prepared in example 1 of the present invention;
FIG. 4 is a fluorescence micrograph of curcumin entrapped in the magnetic controlled release carrier prepared in example 1 of the present invention;
FIG. 5 is a fluorescence micrograph of curcumin embedded in a magnetic controlled release carrier prepared in example 1 according to the present invention after 2min of light irradiation.
Detailed Description
The present invention will be described in further detail with reference to examples, but embodiments of the present invention are not limited thereto.
Preparation of magnetic microparticles:
weighing FeCl 3 ·6H 2 0.2703 g of O (270.3 g/mol) was dissolved in 20mL of water and 0.159 g of Na was weighed 2 CO 3 Dissolved in 5mL of water. Na is mixed with 2 CO 3 Slowly adding FeCl into the solution 3 Magnetically stirring the solution for 30min to obtain Fe (OH) 3 Colloidal solution.
0.1692 g of lauryl gallate (338.44 g/mol) is weighed, 10mL of water is added, and then the mixture is placed on a thermal oscillation reactor, heated to 65 ℃ for oscillation dissolution for 40 minutes, and the mixture is clarified again from suspension to milky liquid, so that the lauryl gallate aqueous solution is obtained.
Fe(OH) 3 After the colloid solution is prepared, adding the dissolved lauryl gallate (lauryl gallate aqueous solution), and magnetically stirring for 10min. Transferring the mixture into a high-pressure heating kettle for reaction for 3 hours at 200 ℃, centrifuging the reaction liquid to remove supernatant after the reaction is finished, washing the supernatant with ethanol for 1 time, washing the supernatant with water for 1 time, and finally freeze-drying the supernatant to obtain the magnetic particles.
Example 1
6mg of the magnetic particles were dissolved in 5mL of water and sonicated at 800W for 10s using a sonicator to obtain a dispersed magnetic particle suspension.
Melting cocoa butter at 60deg.C, taking 1mL of cocoa butter in molten state, adding 0.12g span-60, oscillating at 1500rpm in a heated oscillator at 70deg.C, and mixing well.
Preheating the magnetic particle suspension, mixing with melted cocoa butter (containing span-60), and homogenizing at 14000rpm for 3min to obtain uniform emulsion; after the reaction is completed, the emulsion is quickly transferred into ice bath for cooling, and the pasty magnetic controlled release carrier is obtained, and the magnetic controlled release carrier is kept stable for a long time at room temperature.
The result of observing the magnetic controlled release carrier under an optical microscope is shown in figure 1; it can be seen from fig. 1 that the cocoa butter particles are spherical and that the magnetic particles are embedded on the surface of the butter balls.
The magnetic controlled release carrier is observed under a scanning electron microscope, and the result is shown in figure 2; from fig. 2 it can be seen that the magnetic particles are distributed on the surface of the cocoa butter balls.
The magnetically controlled release carrier was analyzed by line scan spectroscopy and the results are shown in fig. 3; from fig. 3 it can be demonstrated that the small particles on the cocoa butter balls are distributed as magnetic particles.
Curcumin was entrapped as follows:
in the process of preparing the magnetic controlled release carrier, 12mg (the concentration in water is 2.4 mg/mL) of curcumin and the magnetic particle suspension are added into a mixture of melted cocoa butter and an emulsifying agent (span-60) which are uniformly mixed in a homogenizing process after preparing the magnetic particle suspension, and the magnetic controlled release carrier embedded with the curcumin is marked as No. 1 after the homogenizing is finished.
Example 2
4mg of the magnetic particles were dissolved in 5mL of water and sonicated at 800W for 10s using a sonicator to obtain a dispersed magnetic particle suspension. Melting cocoa butter at 60deg.C, taking 1mL of cocoa butter in molten state, adding 0.16g span-60, oscillating at 1500rpm in a heated oscillator at 70deg.C, and mixing well.
Preheating the magnetic particle suspension, mixing with melted cocoa butter (containing span-60), and homogenizing at 14000rpm for 3min to obtain uniform emulsion; after the reaction is completed, the emulsion is quickly transferred into ice bath for cooling, and the pasty magnetic controlled release carrier is obtained, and the magnetic controlled release carrier is kept stable for a long time at room temperature.
Curcumin was entrapped as follows:
in the process of preparing the magnetic controlled release carrier, 8mg (the concentration in water is 1.6 mg/mL) of curcumin and the magnetic particle suspension are added into a mixture of melted cocoa butter and an emulsifying agent in the homogenizing process after preparing the magnetic particle suspension, and the magnetic controlled release carrier embedded with the curcumin is marked as No. 2 after the homogenization is finished.
Example 3
2mg of the magnetic particles were dissolved in 5mL of water and sonicated at 800W for 10s using a sonicator to obtain a dispersed magnetic particle suspension. Melting cocoa butter at 60deg.C, taking 1mL of cocoa butter in molten state, adding 0.24g span-60, oscillating at 1500rpm in a heated oscillator at 70deg.C, and mixing well.
Preheating the magnetic particle suspension, mixing with melted cocoa butter (containing span-60), and homogenizing at 14000rpm for 3min to obtain uniform emulsion; after the reaction is completed, the emulsion is quickly transferred into ice bath for cooling, and the pasty magnetic controlled release carrier is obtained, and the magnetic controlled release carrier is kept stable for a long time at room temperature.
Curcumin was entrapped as follows:
in the process of preparing the magnetic controlled release carrier, 16mg (the concentration in water is 3.2 mg/mL) of curcumin and the magnetic particle suspension are added into a mixture of melted cocoa butter and an emulsifying agent in the homogenizing process after preparing the magnetic particle suspension, and the magnetic controlled release carrier embedded with the curcumin is marked as No. 3 after the homogenization is finished.
Irradiating the 1# magnetic controlled release carrier with an illumination intensity of 1.43A and 100mW, and sampling after the irradiation time is 0min and 2min respectively to obtain carrier samples with different irradiation times; the release of the carrier samples was then observed by confocal fluorescence microscopy at an excitation wavelength of 405nm, and the results are shown in FIGS. 4 and 5.
The curcumin-embedded magnetic controlled release carriers prepared in examples 1 to 3 can be obviously observed in an embedding state under a fluorescence confocal microscope due to the fluorescence absorption effect of curcumin. FIG. 4 is a fluorescence micrograph of a 1# magnetic controlled release carrier with embedded concentration of curcumin of 2.4mg/mL, and FIG. 4 shows that the lipid globules exhibit fluorescence, indicating successful embedding of curcumin by the lipid. And after a certain period of exposure to light, for example, after 2 minutes of exposure to light with an intensity of 1.43A,100mW, the fluorescence micrograph of the No. 1 magnetic controlled release carrier with embedded curcumin at a concentration of 2.4mg/mL is shown in FIG. 5, and it can be seen from FIG. 5 that the lipid globules are in a state of breakage and exposure of active ingredients. The comparison of the results of fig. 4 and 5 to a certain extent illustrates that the carrier construction is completed and that the controlled release effect can be achieved using light and heat.
Claims (4)
1. A method for preparing a magnetic controlled release carrier based on an emulsion system, which is characterized by comprising the following steps:
mixing the magnetic particle suspension, the melted grease and the emulsifying agent, homogenizing, and cooling to obtain the magnetic controlled release carrier;
wherein, the magnetic particle suspension is obtained by dissolving magnetic particles in water and performing ultrasonic dispersion; the magnetic particles are ferroferric oxide magnetic particles with the surfaces modified by lauryl gallate;
the preparation process of the magnetic particles comprises the following steps:
mixing lauryl gallate aqueous solution with Fe (OH) 3 Mixing the colloid solutions, adding the mixture into a high-pressure heating kettle at the temperature of between 150 and 250 ℃ for 1 to 6 hours, and performing post-treatment to obtain magnetic particles;
the melting point of the grease is lower than that of the emulsifier;
the mass volume ratio of the emulsifier to the water in the magnetic particle suspension is 18-50 mg/mL;
in the emulsion system, the concentration of the magnetic particles is 0.3-1.6 mg/mL;
in the emulsion system, the volume ratio of the melted grease to the water is 1: (4-6);
the grease is cocoa butter;
the emulsifier is span-60.
2. The method for preparing a magnetic controlled release carrier based on an emulsion system according to claim 1, wherein in the homogenizing process, the homogenizing speed is 12000-16000 rpm, and the homogenizing time is 1-5 min.
3. A preparation method of a magnetic controlled release carrier loaded with active ingredients is characterized in that the active ingredients to be loaded are mixed with magnetic particle suspension, melted grease and emulsifying agent, homogenized and cooled to obtain the magnetic controlled release carrier loaded with active ingredients;
wherein, the magnetic particle suspension is obtained by dissolving magnetic particles in water and performing ultrasonic dispersion; the magnetic particles are ferroferric oxide magnetic particles with the surfaces modified by lauryl gallate;
the preparation process of the magnetic particles comprises the following steps:
mixing lauryl gallate aqueous solution with Fe (OH) 3 Mixing the colloid solutions, adding the mixture into a high-pressure heating kettle at the temperature of between 150 and 250 ℃ for 1 to 6 hours, and performing post-treatment to obtain magnetic particles;
the melting point of the grease is lower than that of the emulsifier;
the mass volume ratio of the emulsifier to the water in the magnetic particle suspension is 18-50 mg/mL;
in the emulsion system, the concentration of the magnetic particles is 0.3-1.6 mg/mL;
in the emulsion system, the volume ratio of the melted grease to the water is 1: (4-6);
the grease is cocoa butter;
the emulsifier is span-60.
4. A magnetically controlled release carrier based on an emulsion system, characterized in that it is prepared by the preparation method according to any one of claims 1-2.
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| US4331654A (en) * | 1980-06-13 | 1982-05-25 | Eli Lilly And Company | Magnetically-localizable, biodegradable lipid microspheres |
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| BR102016016795A2 (en) * | 2016-07-20 | 2018-02-06 | Universidade Federal Do Ceará | MAGNETIC SOLID LIPID NANOParticles, CARNAUBA WAX BASED WITH POTENTIAL APPLICATION TO MAGNETIC HYPERTERMIA AND MAGNETIC RESONANCE IMAGE |
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| US4331654A (en) * | 1980-06-13 | 1982-05-25 | Eli Lilly And Company | Magnetically-localizable, biodegradable lipid microspheres |
| CN1803134A (en) * | 2005-01-14 | 2006-07-19 | 上海医药工业研究院 | Preparation method of magnetic nanometer granule containing mitocin-C |
| BR102016016795A2 (en) * | 2016-07-20 | 2018-02-06 | Universidade Federal Do Ceará | MAGNETIC SOLID LIPID NANOParticles, CARNAUBA WAX BASED WITH POTENTIAL APPLICATION TO MAGNETIC HYPERTERMIA AND MAGNETIC RESONANCE IMAGE |
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