CN115192543A - Preparation method of fat-soluble pigment-loaded nanoparticles - Google Patents
Preparation method of fat-soluble pigment-loaded nanoparticles Download PDFInfo
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Abstract
The invention relates to the technical field of nano materials, and discloses a preparation method of fat-soluble pigment-loaded nano particles. The carrier mesoporous polydopamine has a high specific surface area and a nano-pore structure, can adsorb hydrophobic drugs, and can greatly improve the loading efficiency of fat-soluble pigments. The polydopamine shell layer taking the modified chitosan as the coating has pH sensitivity and a gating effect, effectively responds to the pH value of a tumor part, improves the effective fat-soluble pigment concentration in a tumor cell, delays the effective action time of the fat-soluble pigment, and improves the poor taste of the fat-soluble pigment; can improve bioavailability and in vivo and in vitro stability of fat-soluble pigment, and improve tumor treatment effect.
Description
Description of the different cases
The invention relates to a divisional application with the application date of 2020, 12 and 31, and the application number of 202011631054X, namely 'fat-soluble pigment-loaded nanoparticle and a preparation method thereof'.
Technical Field
The invention relates to the technical field of nano materials, in particular to a preparation method of fat-soluble pigment-loaded nanoparticles.
Background
Curcumin is a natural effective component extracted from roots of plants of curcuma of zingiberaceae, belongs to a polyphenol compound, has wide pharmacological effects of reducing blood fat, resisting tumors, resisting inflammation, benefiting gallbladder, resisting oxidation, resisting hepatotoxicity, resisting rheumatism, inhibiting bacteria and the like, has low toxicity and good clinical application potential, and has become a hot spot of domestic and foreign research. Lycopene is a carotenoid extracted from plants such as tomatoes, watermelons and the like, is a fat-soluble natural haematochrome, belongs to hydrocarbons, has a strong antioxidation function, has the effects of protecting heart and cerebral vessels, enhancing immunity, resisting tumors and the like, has a prevention or treatment effect on neurodegenerative diseases and mental diseases such as Parkinson, epilepsy and depression, is basically non-toxic in a dosage range, is popular in health care value, and has become a hot spot of domestic and foreign research. Curcumin and lycopene both belong to fat-soluble pigments, and the fat-soluble pigments are insoluble in water, are not easy to absorb when being taken orally, have serious liver first-pass effect, and have higher metabolism and clearing rate in vivo, so the bioavailability is lower, the stability is poor, and the decomposition of visible light is easy, therefore, a proper drug delivery system needs to be prepared to solve the problems, so that the water solubility and the stability of the fat-soluble pigments are improved, the drugs are prevented from being hydrolyzed and oxidized to be inactivated after entering organisms, and the in-vivo release time of the drugs is prolonged. The poly-dopamine (PDA) is a main component of natural biological pigment-melanin, can be obtained by oxidation autopolymerization of dopamine, has good stability, biodegradability, biocompatibility and photothermal conversion characteristics, and is an ideal carrier material. The polydopamine has adhesiveness, and can be coated on the surfaces of various materials. Polydopamine also has pH sensitivity and can be depolymerized in the slightly acidic environment of tumors. The mesoporous polydopamine nanoparticle (MPDA) can be prepared by a soft template method, and can be loaded with a medicament efficiently due to the fact that the MPDA has a pore structure and a high specific surface area, and has good photo-thermal conversion performance. The chitosan is a cationic polymer consisting of glucosamine, has good biocompatibility, low toxicity and biodegradability, has the characteristic of intestinal mucosa adhesion, and is favorable for oral absorption of medicaments as a medicament auxiliary material. The polyethylene glycol modification is carried out on chitosan, so that the adsorption effect of plasma protein on chitosan-coated mesoporous polydopamine nanoparticles can be reduced, the ingestion of macrophages on the chitosan-coated mesoporous polydopamine nanoparticles is reduced, the process that the drug-loaded nanoparticles are removed from plasma is delayed, and the passive targeting function of the chitosan mesoporous polydopamine nanoparticles is further improved through enhanced permeation and retention effects.
Disclosure of Invention
The purpose of the invention is as follows: aiming at the problems in the prior art, the invention provides a preparation method of the nanoparticle carrying the fat-soluble pigment, which can improve the bioavailability of the fat-soluble pigment, improve the water solubility and the stability of the fat-soluble pigment and improve the bioavailability of the fat-soluble pigment, and the nanoparticle carrying the fat-soluble pigment is expected to achieve the aims of tumor penetration and directional slow release.
The technical scheme is as follows: the invention provides a lipid-soluble pigment-loaded nanoparticle, which comprises the following components in a mass ratio of 50 to 59:8 to 13: 5-10 parts of mesoporous polydopamine nanoparticles, a fat-soluble pigment and polyethylene glycol modified chitosan, wherein the mesoporous polydopamine nanoparticles are used as a carrier, the fat-soluble pigment is adsorbed by physical and chemical adsorption, and the polyethylene glycol modified chitosan is wrapped on the outermost layer.
Preferably, the fat-soluble pigment is curcumin or lycopene.
The invention also provides a preparation method of the fat-soluble pigment-loaded nanoparticle, which comprises the following steps: (1) Adding dopamine hydrochloride and Pluronic F127 into an ethanol water solution, stirring at room temperature, then dropwise adding TMB to form a white emulsion, then adding an ammonia water solution, stirring, centrifuging, ultrasonically washing precipitates with ethanol and water for several times, and centrifuging to obtain mesoporous polydopamine nanoparticles which are marked as MPDA; wherein the mass volume ratio of the dopamine hydrochloride, pluronic F127, TMB and the ammonia water solution is 0.3 to 0.5 g:1.0 to 1.2 g:0.6 to 1.0 mL:4.0 to 5.0 mL; (2) Adding the mesoporous polydopamine nanoparticles obtained in the step (1) and fat-soluble pigment powder into anhydrous DMSO, stirring at room temperature for reaction, centrifuging, washing with a mixed solution of DMSO and deionized water and washing with deionized water for several times to obtain fat-soluble pigment-loaded nanoparticles; wherein the mass ratio of the mesoporous polydopamine nanoparticles to the fat-soluble pigment powder is 9 to 11:1; (3) Weighing a certain amount of chitosan and polyethylene glycol, dissolving in dilute acetic acid solution, uniformly mixing, and stirring at room temperature overnight to obtain polyethylene glycol modified chitosan solution; (4) And (3) dissolving the fat-soluble pigment-loaded nanoparticles obtained in the step (2) in an acetic acid aqueous solution, dropwise adding the polyethylene glycol modified chitosan solution obtained in the step (3), stirring at room temperature, centrifuging, and freeze-drying to obtain the fat-soluble pigment-loaded nanoparticles.
Preferably, in the step (1), the volume ratio of ethanol to water in the ethanol aqueous solution is 1:1.
preferably, in the step (2), in the DMSO deionized water mixed solution, the volume ratio of DMSO to deionized water is 3 to 4:7 to 8.
Preferably, in the step (3), the mass ratio of chitosan to polyethylene glycol is 1:0.2 to 0.3.
Preferably, in the step (3), the mass fraction of the dilute acetic acid aqueous solution is 1 to 2%.
Preferably, in the step (4), the mass fraction of the acetic acid aqueous solution is 0.5 to 1%.
Preferably, in the step (4), the freeze drying temperature is-40 to-70 ℃, and the freeze drying time is 12 to 24 hours.
Has the beneficial effects that: compared with the prior art, the invention has the following beneficial effects:
(1) The drug-loaded mesoporous polydopamine nanoparticle which can improve the bioavailability of the fat-soluble pigment and is coated by the modified chitosan is constructed by taking polydopamine as a base material, synthesizing mesoporous polydopamine nanoparticles, loading the fat-soluble pigment and coating modified chitosan molecules, so that the water solubility and stability of the fat-soluble pigment are improved, the bioavailability of the fat-soluble pigment is improved, and the drug-loaded nanoparticle is expected to achieve the purposes of tumor penetration and directional slow release.
(2) The carrier Mesoporous Polydopamine (MPDA) has a high specific surface area and a nano-pore structure, has strong adsorption capacity, can adsorb hydrophobic drug fat-soluble pigments on the surface and in pores of the mesoporous polydopamine, can generate pi-pi electron transition, forms carbonyl bonds (the fat-soluble pigments are curcumin) or has a michael addition reaction (the fat-soluble pigments are lycopene) with fat-soluble pigment molecules, and can greatly improve the loading efficiency of the polydopamine on the fat-soluble pigments by combining physical adsorption and chemical adsorption.
(3) The fat-soluble pigment-loaded nanoparticle of the invention ensures that the release of fat-soluble pigment has pH responsiveness and a gating effect, can effectively respond to the pH value of a tumor part, improve the effective fat-soluble pigment concentration in a tumor cell, delay the effective action time of the fat-soluble pigment, improve the poor taste of the fat-soluble pigment and avoid bitter components of some fat-soluble pigments from being dissolved in the mouth.
(4) The modified chitosan can be absorbed and utilized by human bodies, has good biocompatibility and biodegradability, chitosan oligosaccharide generated in the degradation process is not accumulated in the bodies, almost has no immunogenicity, and has good water solubility. The chitosan can be adsorbed in intestinal tract to delay discharge, so that the fat-soluble pigment absorbed by human body is more, the bioavailability is improved, and the chitosan coated on the surface can improve the storage stability of the granule.
(5) The mesoporous polydopamine carrier constructed by the invention is safe, non-toxic, simple to prepare, single in component, capable of improving the stability of fat-soluble pigment and convenient to store.
Drawings
Fig. 1 is a particle size distribution diagram of a mesoporous polydopamine carrier and mesoporous polydopamine curcumin-loaded nanoparticles;
FIG. 2 is a transmission electron microscope image of mesoporous polydopamine carrier and mesoporous polydopamine curcumin-loaded nanoparticle;
FIG. 3 is a nitrogen adsorption/desorption graph of mesoporous polydopamine MPDA;
FIG. 4 biological safety examination of blank vector on human normal hepatocyte LO 2;
FIG. 5 is a slow release curve diagram of mesoporous polydopamine curcumin-loaded nanoparticles in simulated gastric and intestinal fluids;
FIG. 6 is a particle size distribution diagram of mesoporous polydopamine carrier and mesoporous polydopamine-loaded lycopene nanoparticles;
FIG. 7 is a transmission electron microscope image of mesoporous polydopamine carrier and mesoporous polydopamine-loaded lycopene nanoparticles;
FIG. 8 is a graph showing the photostability of lycopene, mesoporous polydopamine-loaded lycopene nanoparticles;
fig. 9 is a slow release curve diagram of mesoporous polydopamine-loaded lycopene nanoparticles in simulated gastric and intestinal fluids.
FIG. 10 shows the cytotoxic effect of mesoporous polydopamine nanoparticles on liver cancer cells HepG 2.
Detailed Description
The present invention will be described in detail with reference to the accompanying drawings.
Embodiment 1:
the embodiment provides a preparation method of a mesoporous polydopamine curcumin-loaded nanoparticle PEG-CS @ MPDA @ CUR, which is implemented according to the following steps:
step 1, synthesis of MPDA
To a mixed solution of ethanol water (1; adding 4.0 mL of ammonia water solution, stirring for 30 min at 50 ℃, centrifuging, ultrasonically washing the precipitate for 3 times by using ethanol and water, and centrifuging to obtain mesoporous polydopamine nanoparticles marked as MPDA;
Mixing mesoporous polydopamine nanoparticles and curcumin powder according to a mass ratio of 8:1, stirring and reacting for 24 hours at room temperature, centrifuging, washing once by using a mixed solution of DMSO and deionized water (3, 7, v/v) and washing 3 times by using the deionized water to obtain curcumin-loaded nanoparticles, which are marked as MPDA @ CUR;
step 3, synthesis of PEG-CS @ MPDA @ CUR
Weighing 1 g of chitosan and 0.2 g of polyethylene glycol, dissolving in 1% diluted acetic acid solution, uniformly mixing, and stirring at room temperature overnight to obtain polyethylene glycol modified chitosan solution; dissolving the curcumin-loaded nanoparticles in 100 mL of 0.5% acetic acid water, dropwise adding 20 mL of polyethylene glycol modified chitosan solution, stirring at room temperature, centrifuging, and freeze-drying at-60 ℃ for 16 h to obtain the mesoporous polydopamine curcumin-loaded nanoparticles PEG-CS @ MPDA @ CUR.
The prepared mesoporous polydopamine curcumin-loaded nanoparticle PEG-CS @ MPDA @ CUR comprises the following components in percentage by mass: 8:5, the mesoporous polydopamine nanoparticle is used as a carrier, and the curcumin is physically and chemically adsorbed, and the polyethylene glycol modified chitosan is wrapped on the outermost layer.
Embodiment 2:
a preparation method of mesoporous polydopamine curcumin-loaded nanoparticles is specifically implemented according to the following steps:
step 1, synthesis of MPDA
Adding 0.5 g of dopamine hydrochloride and 1.2 g of Pluronic F127 into a mixed solution of ethanol water (1;
Mixing mesoporous polydopamine nanoparticles and curcumin powder according to a mass ratio of 9:1, stirring and reacting for 12 hours at room temperature, centrifuging, washing once by using a mixed solution of DMSO and deionized water (4, 7, v/v) and washing 5 times by using the deionized water to obtain curcumin-loaded nanoparticles marked as MPDA @ CUR;
step 3, synthesis of PEG-CS @ MPDA @ CUR
Weighing 1 g of chitosan and 0.3 g of polyethylene glycol, dissolving in 2% diluted acetic acid solution, uniformly mixing, and stirring at room temperature overnight to obtain polyethylene glycol modified chitosan solution; dissolving the curcumin-loaded nanoparticles in 100 mL of 0.5% acetic acid water, dropwise adding 20 mL of polyethylene glycol modified chitosan solution, stirring at room temperature, centrifuging, and freeze-drying at-40 ℃ for 24 h to obtain the mesoporous polydopamine curcumin-loaded nanoparticles PEG-CS @ MPDA @ CUR.
The prepared mesoporous polydopamine curcumin-loaded nanoparticle PEG-CS @ MPDA @ CUR comprises the following components in mass ratio of 55:9:7, the mesoporous polydopamine nanoparticle is used as a carrier, and the curcumin is physically and chemically adsorbed, and the polyethylene glycol modified chitosan is coated on the outermost layer.
Embodiment 3:
a preparation method of mesoporous polydopamine curcumin-loaded nanoparticles is specifically implemented according to the following steps:
step 1, synthesis of MPDA
Adding 0.3 g of dopamine hydrochloride and 0.5 g of Pluronic F127 into a mixed solution of ethanol water (1;
Adding mesoporous polydopamine nanoparticles and curcumin powder into anhydrous DMSO according to a mass ratio of 10;
step 3, synthesis of PEG-CS @ MPDA @ CUR
Weighing 1 g of chitosan and 0.2 g of polyethylene glycol, dissolving in 1% diluted acetic acid solution, uniformly mixing, and stirring at room temperature overnight to obtain polyethylene glycol modified chitosan solution; dissolving the curcumin-loaded nanoparticles in 100 mL of 0.5% acetic acid water, dropwise adding 20 mL of polyethylene glycol modified chitosan solution, stirring at room temperature, centrifuging, and freeze-drying at-40 ℃ for 24 h to obtain the mesoporous polydopamine curcumin-loaded nanoparticles PEG-CS @ MPDA @ CUR.
The prepared mesoporous polydopamine curcumin-loaded nanoparticle PEG-CS @ MPDA @ CUR comprises the following components in mass ratio of 52:9:6, the mesoporous polydopamine nanoparticle is used as a carrier, and the curcumin is physically and chemically adsorbed, and the polyethylene glycol modified chitosan is wrapped on the outermost layer.
The particle size distribution of the mesoporous polydopamine carrier and the mesoporous polydopamine curcumin-loaded nanoparticle in the embodiments 1 to 3 was analyzed by a malvern laser particle sizer. The mesoporous polydopamine carrier and the mesoporous polydopamine curcumin-loaded nanoparticle are dispersed in water, and the particle size distribution is measured, as shown in figure 1, the hydrodynamic diameter sizes are 125 +/-10 nm and 135 +/-10 nm respectively.
The shapes of the mesoporous polydopamine carrier and the mesoporous polydopamine curcumin-loaded nanoparticle in the embodiments 1 to 3 are observed by a Transmission Electron Microscope (TEM): and (3) dropwise adding 10 mu L of the solution on a surface carbon coating copper net, and naturally drying at room temperature. And under the condition of 200KV voltage, the appearance, the particle size and the dispersion condition of the nano particles are observed by a transmission electron microscope. The transmission electron microscope picture of the carrier is shown in fig. 2, and the MPDA prepared has a narrow particle size distribution range, uniform particle size and an obvious pore structure on the surface.
MPDA nitrogen adsorption/desorption curve determination: taking an oven-dried 80 mg MPDA sample, determining a nitrogen adsorption/desorption curve by an instrument, and calculating the specific surface area of the prepared MPDA nanoparticles by using a BJH method to be 63.6510 m/g as shown in FIG. 3.
The growth inhibition of the blank vector on human normal hepatocyte LO2 was examined by MTT method. Human normal hepatocyte LO2 is used, blank carrier solutions with different concentrations are added into the experimental group at 200 muL/hole, culture solutions with 200 muL/hole are added into the control group, and cell viability of human normal hepatocyte LO2 under different concentration conditions is inspected by taking relative cell viability as an inspection index under two pH conditions. As shown in FIG. 4, when the concentration of the blank nanoparticles reaches 1000. Mu.g/mL, the survival rate of the LO2 cells of normal human hepatocytes is also above 80%, which indicates that the carrier material has good biocompatibility within the concentration of 0.98 to 1000. Mu.g/mL.
The release conditions of the mesoporous polydopamine curcumin-loaded nanoparticle in the embodiments 1 to 3 in simulated gastric fluid and simulated intestinal fluid are examined by adopting a dialysis bag method. Placing 1 mL of mesoporous polydopamine curcumin-loaded nanoparticle suspension in a dialysis bag, wherein release media are simulated artificial gastric juice and artificial intestinal juice, oscillating at constant temperature of 37 ℃, sampling at different time points, and drawing an accumulated drug release curve. The experimental result is shown in fig. 5, and it can be seen from the figure that the release rate of the mesoporous polydopamine curcumin-loaded nanoparticle in simulated gastric fluid is higher than that in simulated intestinal fluid, the cumulative release rate is greater than 80%, and the release is relatively complete. And the mesoporous polydopamine curcumin-loaded nanoparticle is slowly released from the beginning of the experiment and is gradually stable along with the lapse of time, which shows that the mesoporous polydopamine curcumin-loaded nanoparticle has a remarkable effect in the aspect of curcumin controlled release.
Embodiment 4:
the embodiment provides a preparation method of mesoporous polydopamine-loaded lycopene nanoparticle PEG-CS @ MPDA @ LYC, which is implemented according to the following steps:
step 1, synthesis of MPDA
To a mixed solution of ethanol water (1; adding 4.5 mL of ammonia water solution, stirring for 30 min at 50 ℃, centrifuging, ultrasonically washing the precipitate for 3 times by using ethanol and water, and centrifuging to obtain mesoporous polydopamine nanoparticles marked as MPDA;
Mixing mesoporous polydopamine nanoparticles and lycopene powder according to a mass ratio of 9:1, stirring and reacting for 24 hours at room temperature, centrifuging, washing once with a mixed solution of DMSO and deionized water (4, 7, v/v) and washing 3 times with deionized water to obtain lycopene-loaded nanoparticles, which are marked as MPDA @ LYC;
step 3, synthesis of PEG-CS @ MPDA @ LYC
Weighing 1 g of chitosan and 0.25 g of polyethylene glycol, dissolving in 2% diluted acetic acid solution, uniformly mixing, and stirring at room temperature overnight to obtain polyethylene glycol modified chitosan solution; dissolving the lycopene-loaded nanoparticles in 100 mL of 0.5% acetic acid water, dropwise adding 20 mL of polyethylene glycol modified chitosan solution, stirring at room temperature, centrifuging, and freeze-drying at-40 ℃ for 24 h to obtain the mesoporous polydopamine-loaded lycopene nanoparticles PEG-CS @ MPDA @ LYC.
The prepared mesoporous polydopamine-loaded lycopene nanoparticle PEG-CS @ MPDA @ LYC comprises the following components in mass ratio of 50:9:6, the mesoporous polydopamine nanoparticle, the lycopene and the polyethylene glycol modified chitosan are used as carriers, and the lycopene is physically and chemically adsorbed by the mesoporous polydopamine nanoparticle, and the polyethylene glycol modified chitosan is coated on the outermost layer.
Embodiment 5:
a preparation method of mesoporous polydopamine-loaded lycopene nanoparticles is implemented according to the following steps:
step 1, synthesis of MPDA
Adding 0.5 g of dopamine hydrochloride and 1.0 g of Pluronic F127 into a mixed solution of ethanol water (1;
Mixing mesoporous polydopamine nanoparticles and lycopene powder according to a mass ratio of 10:1, stirring and reacting for 12 hours at room temperature, centrifuging, washing once by using a mixed solution of DMSO and deionized water (3, 7, v/v) and washing 5 times by using the deionized water to obtain lycopene-loaded nanoparticles, wherein the lycopene-loaded nanoparticles are marked as MPDA @ LYC;
step 3, synthesis of PEG-CS @ MPDA @ LYC
Weighing 1 g of chitosan and 0.2 g of polyethylene glycol, dissolving in 1.5% diluted acetic acid solution, uniformly mixing, and stirring at room temperature overnight to obtain polyethylene glycol modified chitosan solution; dissolving the lycopene-loaded nanoparticles in 100 mL of 1.0% acetic acid water, dropwise adding 20 mL of polyethylene glycol modified chitosan solution, stirring at room temperature, centrifuging, and freeze-drying at-40 ℃ for 24 h to obtain the mesoporous polydopamine-loaded lycopene nanoparticles PEG-CS @ MPDA @ LYC.
The prepared mesoporous polydopamine-loaded lycopene nanoparticle PEG-CS @ MPDA @ LYC comprises the following components in mass ratio of 54:11:8, the mesoporous polydopamine nanoparticle, lycopene and polyethylene glycol modified chitosan are used as carriers, and the lycopene is physically and chemically adsorbed by the mesoporous polydopamine nanoparticle, and the polyethylene glycol modified chitosan is coated on the outermost layer.
Embodiment 6:
a preparation method of mesoporous polydopamine-loaded lycopene nanoparticles is specifically implemented according to the following steps:
step 1, synthesis of MPDA
Adding 0.4 g of dopamine hydrochloride and 1.2 g of Pluronic F127 into a mixed solution of ethanol water (1, 1 v/v), stirring at room temperature, then dropwise adding 0.8 mL of TMB to form a white emulsion, adding 4 mL of ammonia water solution, stirring for 30 min at 40 ℃, carrying out centrifugation, ultrasonically washing the precipitate for 5 times by using ethanol and water, and centrifuging to obtain mesoporous polydopamine nanoparticles, wherein the mesoporous polydopamine nanoparticles are marked as MPDA;
Adding mesoporous polydopamine nanoparticles and lycopene powder into anhydrous DMSO according to the mass ratio of 11;
step 3, synthesis of PEG-CS @ MPDA @ LYC
Weighing 1 g of chitosan and 0.3 g of polyethylene glycol, dissolving in 2% diluted acetic acid solution, uniformly mixing, and stirring at room temperature overnight to obtain polyethylene glycol modified chitosan solution; dissolving the lycopene-loaded nanoparticles in 100 mL of 0.5% acetic acid water, dropwise adding 20 mL of polyethylene glycol modified chitosan solution, stirring at room temperature, centrifuging, and freeze-drying at-40 ℃ for 24 h to obtain the mesoporous polydopamine-loaded lycopene nanoparticles PEG-CS @ MPDA @ LYC.
The prepared mesoporous polydopamine-loaded lycopene nanoparticle PEG-CS @ MPDA @ LYC comprises the following components in mass ratio of 56:11:7, the mesoporous polydopamine nanoparticle, lycopene and polyethylene glycol modified chitosan are used as carriers, and the lycopene is physically and chemically adsorbed by the mesoporous polydopamine nanoparticle, and the polyethylene glycol modified chitosan is coated on the outermost layer.
The particle size distribution of the mesoporous polydopamine carrier and the mesoporous polydopamine lycopene nanoparticle in the embodiments 4 to 6 was analyzed by a malvern laser particle size analyzer. The mesoporous polydopamine carrier and the mesoporous polydopamine-loaded lycopene nanoparticle are dispersed in water, and the particle size distribution of the mesoporous polydopamine-loaded lycopene nanoparticle is measured, as shown in fig. 6, wherein the hydrodynamic diameters of the mesoporous polydopamine-loaded lycopene nanoparticle are 125 +/-10 nm and 140 +/-10 nm respectively.
The shapes of the mesoporous polydopamine carrier and the mesoporous polydopamine-loaded lycopene nanoparticle in the embodiments 4 to 6 are observed by a Transmission Electron Microscope (TEM): and (3) dropwise adding 10 mu L of the solution on a surface carbon coating copper net, and naturally air-drying at room temperature. And under the condition of 200KV voltage, the appearance, the particle size and the dispersion condition of the nano particles are observed by a transmission electron microscope. The transmission electron microscope picture of the carrier is shown in fig. 7a, and the prepared MPDA has a narrow particle size distribution range, uniform particle size and an obvious pore structure on the surface. As shown in fig. 7b, it can be seen that the mesoporous polydopamine-loaded lycopene nanoparticle has a uniform particle size and a spherical shape, and the regularly distributed pores become fuzzy due to the adsorption of lycopene on the surface and the modification of chitosan.
Placing a certain amount of lycopene-loaded nanoparticles and lycopene powder in an indoor scattered light environment, paving, carrying out full light irradiation to enable light energy to be in contact with each surface of lycopene, weighing a certain amount of powder at 0 h, 2 h, 4 h, 6 h, 8 h, 10 h and 12 h respectively at 25 ℃, adding 10 mL of DMSO for full dissolution, carrying out ultrasonic treatment for 10 min, repeating 3 times to obtain an average value, and measuring the content respectively by using an ultraviolet spectrophotometer method. As shown in figure 8, the stability of the lycopene is obviously improved by preparing the nano capsule, and the content of the lycopene is improved to about 98.72 percent from 80.75 percent before original non-adsorption embedding after 12 hours.
A dialysis bag method is adopted to investigate the release conditions of the mesoporous polydopamine lycopene-loaded nanoparticles in the embodiments 4 to 6 in simulated gastric fluid and simulated intestinal fluid. Placing 1 mL of mesoporous polydopamine lycopene nanoparticle suspension in a dialysis bag, wherein release media are simulated artificial gastric juice and artificial intestinal juice, oscillating at constant temperature of 37 ℃, sampling at different time points, and drawing an accumulated drug release curve. The experimental result is shown in fig. 9, and it can be seen from the figure that the release rate of the mesoporous polydopamine-loaded lycopene nanoparticle in simulated gastric fluid is higher than that in simulated intestinal fluid, the cumulative release rate is also higher than 80%, and the release is relatively complete. And the mesoporous polydopamine-loaded lycopene nanoparticle is slowly released from the beginning of an experiment and is gradually stable along with the lapse of time, which shows that the mesoporous polydopamine-loaded lycopene nanoparticle has a remarkable effect in the aspect of lycopene controlled release.
The toxicity effect of free lycopene, PEG-CS @ MPDA @ LYC on human hepatoma cell HepG2 was examined by MTT test. The results are shown in fig. 10, and lycopene shows obvious dose-dependent inhibition effect on human liver cancer cell HepG2 under two pH conditions. This enhanced anti-tumor effect of lycopene upon carrier loading may be due to the excellent anti-proliferative activity of the chelated lycopene and the synergistic anti-tumor effect of lycopene and the surface-modified chitosan coating.
The above embodiments are merely illustrative of the technical concepts and features of the present invention, and the purpose of the embodiments is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (7)
1. A preparation method of fat-soluble pigment-loaded nanoparticles is characterized by comprising the following steps:
(1) Adding dopamine hydrochloride and Pluronic F127 into an ethanol aqueous solution, stirring at room temperature, then adding TMB dropwise to form a white emulsion, then adding an ammonia aqueous solution, stirring, centrifuging, ultrasonically washing the precipitate with ethanol and water for several times, and centrifuging to obtain mesoporous polydopamine nanoparticles, wherein the mesoporous polydopamine nanoparticles are marked as MPDA;
wherein the mass volume ratio of the dopamine hydrochloride, pluronic F127, TMB and the ammonia water solution is 0.3 to 0.5 g:1.0 to 1.2 g:0.6 to 1.0 mL:4.0 to 5.0 mL;
(2) Adding the mesoporous polydopamine nanoparticles obtained in the step (1) and fat-soluble pigment powder into anhydrous DMSO, stirring at room temperature for reaction, centrifuging, washing with a mixed solution of DMSO and deionized water and washing with deionized water for several times to obtain fat-soluble pigment-loaded nanoparticles;
wherein the mass ratio of the mesoporous polydopamine nanoparticles to the fat-soluble pigment powder is 9 to 11:1;
(3) Weighing a certain amount of chitosan and polyethylene glycol, dissolving in dilute acetic acid solution, uniformly mixing, and stirring at room temperature overnight to obtain polyethylene glycol modified chitosan solution;
(4) And (3) dissolving the fat-soluble pigment-loaded nanoparticles obtained in the step (2) in an acetic acid aqueous solution, dropwise adding the polyethylene glycol modified chitosan solution obtained in the step (3), stirring at room temperature, centrifuging, and freeze-drying to obtain the fat-soluble pigment-loaded nanoparticles.
2. The method for preparing the nanoparticle carrying fat-soluble pigment according to claim 1, wherein in the step (1), the volume ratio of ethanol to water in the ethanol aqueous solution is 1:1.
3. the method for preparing the fat-soluble pigment nanoparticle-loaded compound according to claim 1, wherein in the step (2), the volume ratio of the DMSO to the deionized water in the mixed solution of the DMSO and the deionized water is 3-4: 7 to 8.
4. The method for preparing the fat-soluble pigment nanoparticle-loaded compound according to claim 1, wherein in the step (3), the mass ratio of the chitosan to the polyethylene glycol is 1.
5. The method for preparing the mesoporous polydopamine-loaded lipid-soluble nanoparticle as claimed in claim 4, wherein in the step (3), the mass fraction of the dilute acetic acid aqueous solution is 1-2%.
6. The method for preparing the lipid-soluble pigment nanoparticle-loaded according to claim 1, wherein in the step (4), the mass fraction of the aqueous solution of acetic acid is 0.5 to 1%.
7. The method for preparing lipid soluble pigment nanoparticle-loaded according to any one of claims 1 to 6, wherein in the step (4), the temperature of freeze drying is from-40 ℃ to-70 ℃, and the time of freeze drying is from 12 to 24 hours.
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| CN115192543B (en) | 2023-06-30 |
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Application publication date: 20221018 Assignee: Zibo Hefeng Seed Technology Co.,Ltd. Assignor: HUAIYIN INSTITUTE OF TECHNOLOGY Contract record no.: X2023990000959 Denomination of invention: Preparation method of lipid soluble pigment nanoparticles Granted publication date: 20230630 License type: Common License Record date: 20231205 |