CN117643637B - Controlled release carrier for improving biological accessibility of curcumin and preparation method thereof - Google Patents
Controlled release carrier for improving biological accessibility of curcumin and preparation method thereof Download PDFInfo
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- 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 title claims abstract description 229
- 229940109262 curcumin Drugs 0.000 title claims abstract description 114
- 235000012754 curcumin Nutrition 0.000 title claims abstract description 114
- 239000004148 curcumin Substances 0.000 title claims abstract description 114
- 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 title claims abstract description 114
- 238000013270 controlled release Methods 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a controlled release carrier for improving biological accessibility of curcumin and a preparation method thereof, belonging to the field of curcumin delivery carriers. The invention constructs succinic acid cyclodextrin ester/chitosan (SACD/CS) nano particles as an upper digestive tract delivery carrier of curcumin; wherein cyclodextrin Succinate (SACD) plays a role in promoting the dispersion of curcumin in water matrix; chitosan (CS), a natural polymer that is not degraded by digestive enzymes in the upper digestive tract, can immobilize curcumin in its macromolecular network and achieve controlled release during digestion. The carrier prepared by the invention is formed based on electrostatic interaction self-assembly, and the preparation process is safe, simple and efficient, and has wide application prospect in the fields of foods, medicines and the like.
Description
Technical Field
The invention relates to a controlled release carrier for improving biological accessibility of curcumin and a preparation method thereof, belonging to the field of curcumin delivery carriers.
Background
Curcumin is a natural phenolic compound separated from turmeric, has physiological activities of antioxidation, anti-inflammatory, anticancer, antibiosis and the like, and has wide application in the health fields of foods, medicines and the like. However, curcumin has extremely poor water solubility, is difficult to disperse in water-based digestive juice after being taken in through the oral cavity and entering the human digestive tract, and only sufficiently dispersed curcumin can be absorbed by intestinal epithelial cells into the human body. Promoting the dispersion of curcumin in digestive juice is one of the key technologies to improve its bioavailability.
Literature （Yao Hu, et al. Encapsulation, protection, and delivery of curcumin using succinylated-cyclodextrin systems with strong resistance to environmental and physiological stimuli,Food Chemistry,Volume 376,2022,131869.） has achieved excellent results by embedding curcumin in the cavities of water-soluble cyclodextrin molecules, which effectively improves its dispersibility in aqueous matrices. However, due to the high water solubility of the prepared curcumin-cyclodextrin inclusion compound, the curcumin is released completely immediately after entering the alimentary canal, and the sudden release effect enables human bodies to absorb high-concentration curcumin in a short time, so that potential toxic and side effects can be generated. Therefore, a technical difficulty in improving the bioavailability of curcumin is to control the release rate of curcumin in the digestive tract, thereby making it highly effective in exerting the bioavailability.
Curcumin is ingested and then sequentially passes through the upper digestive tract (oral cavity-stomach-small intestine) and the lower digestive tract (large intestine), and the non-digested and absorbed curcumin finally exits the body along with feces. In the upper digestive tract process, curcumin dispersed into digestive juice under the action of digestive enzymes, bile salts and the like can be directly absorbed by digestive tract epithelial cells; in the lower digestive tract, curcumin produces a series of metabolites under the action of intestinal microorganisms, and the physiological activity of the metabolites is correspondingly changed. The upper and lower digestive tract processes belong to two completely different processes, and a carrier that can be used for the lower digestive tract process is not necessarily used for the upper digestive tract carrier. Generally, the bioavailability of curcumin refers to the content of curcumin dispersed in the upper digestive tract and absorbed by the human body. Constructing an upper gastrointestinal delivery vehicle of curcumin is the most promising technical means for improving the biological accessibility of curcumin at present.
The literature (Wang Yurong, feng, megaly, et al, preparation of carboxymethylated bletilla polysaccharide-chitosan curcumin-loaded polyelectrolyte composite membrane and its characterization [ J ]. Chinese herbal medicines, 2020, 51 (4): 8.DOI: 10.7501/j.issn.0253-2670.2020.04.023.) discloses a method for preparing carboxymethylated bletilla polysaccharide-chitosan curcumin-loaded polyelectrolyte composite membrane, mainly for oral cavity release; CN115607524a discloses a composite nanoparticle loaded with curcumin, which is of a shell-core structure, wherein curcumin and zein are taken as cores, and carboxymethyl pachyman is taken as a shell; CN 108653721a discloses chitosan carrier drugs of water-soluble curcumin derivatives; CN104273522B discloses the preparation of curcumin nanocomposites, wherein lecithin and tween-80 are required as emulsifiers; but still has the problems of low biological accessibility of curcumin, high energy load brought by grease carriers, use of small molecule emulsifying agents and the like with potential toxic components and the like.
Disclosure of Invention
[ Technical problem ]
Curcumin carriers or compounds have the problems of low biological accessibility, high energy load caused by grease carriers, use of potential toxic components such as small molecule emulsifying agents and the like.
Technical scheme
In order to solve the problems, the invention constructs succinic acid cyclodextrin ester/chitosan (SACD/CS) nano particles as an upper digestive tract delivery carrier of curcumin; wherein cyclodextrin Succinate (SACD) plays a role in promoting the dispersion of curcumin in water matrix; chitosan (CS), a natural polymer that is not degraded by digestive enzymes in the upper digestive tract, can immobilize curcumin in its macromolecular network and achieve controlled release during digestion. The carrier prepared by the invention is formed based on electrostatic interaction self-assembly, and the preparation process is safe, simple and efficient, and has wide application prospect in the fields of foods, medicines and the like.
A first object of the present invention is to provide a method for preparing a controlled release nanocarrier Cur-SACD/CS that improves the bioavailability of curcumin, comprising the steps of:
(1) Preparation of SACD/CS nanoparticles:
Slowly adding the cyclodextrin succinate SACD solution into the chitosan CS solution, and stirring for reaction; slowly dripping ethanol, continuously stirring to promote particle formation, and after the reaction is finished, carrying out solid-liquid separation, washing and drying to obtain SACD/CS nano particles; wherein, the mass ratio of SACD in SACD solution to CS in CS solution is 1:1-5;
(2) SACD/CS nanoparticle loading curcumin:
Dispersing SACD/CS nano-particles in water, and hydrating to obtain SACD/CS nano-particle suspension; adding the curcumin solution into the SACD/CS nanoparticle suspension, and stirring for reaction in a dark place; after the reaction is finished, carrying out solid-liquid separation and drying to obtain the nano-carrier Cur-SACD/CS.
In one embodiment of the present invention, the solvent of the SACD solution in step (1) is acetic acid-sodium acetate buffer with ph=5.3, and the concentration is 0.001-10 g/mL, more preferably 0.01 g/mL.
In one embodiment of the present invention, the CS solution in step (1) is prepared by: dissolving CS in glacial acetic acid solution, and then adopting sodium hydroxide solution to adjust the pH value to 5.3; wherein, the dosage ratio of CS to glacial acetic acid solution is 0.1-2 g:100 mL; the mass concentration of the glacial acetic acid solution is 0.5-1.5%; the concentration of the sodium hydroxide solution is 0.1-0.3 mol/L.
In one embodiment of the present invention, the rate of slow addition in step (1) is from 20 to 200 mL/min.
In one embodiment of the present invention, the stirring reaction in step (1) is 100-600 rpm stirring reaction 10-30 min.
In one embodiment of the invention, the slow dropping speed in step (1) is 1-10 mL/min.
In one embodiment of the present invention, the ethanol in step (1) is absolute ethanol.
In one embodiment of the invention, the ratio of CS to ethanol used in step (1) is 1g: 350-450 mL.
In one embodiment of the invention, the continuous stirring in step (1) is stirring the reaction at 100-600 rpm for 30-90 min.
In one embodiment of the present invention, the solid-liquid separation in step (1) is to collect SACD/CS nanoparticles therein by centrifugation or suction filtration.
In one embodiment of the present invention, the washing in step (1) is performed with an aqueous ethanol solution having a volume fraction of 60 to 80% for 1 to 5 times.
In one embodiment of the invention, the SACD/CS nanoparticle dispersion and water usage ratio in the SACD/CS nanoparticle suspension in step (2) is 0.5 g:40-100 mL.
In one embodiment of the invention, the hydration in step (2) is carried out by stirring the reaction at 100 to 300 rpm a with 20 to 40a min a.
In one embodiment of the invention, the concentration of the curcumin solution in step (2) is 0.5-5 mg/mL; the solvent is absolute ethyl alcohol.
In one embodiment of the invention, the volume ratio of curcumin solution and SACD/CS nanoparticle suspension in step (2) is 0.5:40-100.
In one embodiment of the present invention, the stirring reaction in step (2) is a stirring reaction of 2 to 4h at 100 to 300 rpm.
In one embodiment of the invention, the solid-liquid separation in the step (2) is to collect Cur-SACD/CS nano-carriers therein by adopting centrifugation or suction filtration.
The second purpose of the invention is to prepare the nano-carrier Cur-SACD/CS by the method.
The third purpose of the invention is to apply the nano-carrier Cur-SACD/CS prepared by the method in the field of food or medicines.
The fourth object of the invention is to provide a method for improving the controlled slow release effect and the upper digestive tract release amount of curcumin, which adopts the nano carrier Cur-SACD/CS.
[ Advantageous effects ]
(1) The invention solves the problem of low biological accessibility of curcumin, and prepares the curcumin controlled release carrier based on an electrostatic self-assembly technology. According to the invention, CS is adopted as a natural macromolecular network, and is self-assembled with SACD through electrostatic interaction to form the SACD/CS nanoparticle carrier, so that the controlled release of the upper digestive tract of the curcumin is realized after the curcumin is loaded, and the biological accessibility of the curcumin is effectively improved.
(2) The SACD/CS nano-particles are prepared based on the electrostatic self-assembly technology, the preparation process is simple, green and nontoxic, and the morphology of the SACD/CS nano-particles can be regulated and controlled by controlling the proportion of SACD to CS. In the simulated in vitro digestion process, the curcumin in the Cur-SACD/CS nano-carrier realizes the delay control delivery.
(3) The particle size of the nano carrier Cur-SACD/CS prepared by the invention is about 200 nm and is far lower than the conventional carrier size of more than 1000 nm.
Drawings
FIG. 1 is an SEM image of SACD/CS complexes prepared in examples 1-3 and comparative examples 1-3, wherein (a) comparative example 1 (0:5); (b) comparative example 2 (1:5); (c) comparative example 3 (3:5); (d) example 1 (5:5); (e) example 2 (7:5); (f) example 3 (9:5).
FIG. 2 is a FTIR spectrum of SACD/CS complexes prepared in examples 1-3 and comparative examples 2-3.
FIG. 3 shows the release of curcumin at various stages of in vitro simulated digestion of the nanocarriers prepared in examples 1-3 and comparative examples 1-3.
FIG. 4 shows the retention rate of curcumin in Cur-SACD/CS nanocarriers prepared in example 1 after incubation at simulated gastric fluid pH (a), intestinal fluid pH (b), physiological salt concentration (c) and physiological temperature (d) (I-VI show that the difference between samples is significant, and p < 0.05).
Fig. 5 is a loading curve of curcumin for the nanocarriers prepared in example 1 and comparative example 1.
FIG. 6 is an SEM image of a SACD/CS complex prepared according to comparative example 4.
Detailed Description
The following description of the preferred embodiments of the present invention is provided for better illustration of the invention, and should not be construed as limiting the invention.
The testing method comprises the following steps:
1. In vitro simulated digestion and release test of Cur-SACD/CS nanocarriers:
(1) Simulation of oral digestion: dispersing a 1g to-be-tested sample in 10mL simulated oral digestive juice (containing 1.5 mg/mL mucin and 75U/mL salivary amylase), and incubating at 37 ℃ at 150 rpm for 2 min;
(2) Gastric digestion was simulated: the 10 mL reacted oral digest was added to 10 mL simulated gastric fluid (containing 2000U/mL pepsin and 60U/mL gastric lipase) and the gastric digest was then adjusted to ph=3 with 5 mol/L HCl solution and incubated 2h at 37 ℃,150 rpm;
(3) Simulation of small intestine digestion: the gastric digest after reaction of 20mL was adjusted to ph=7 with 5mol/L NaOH solution, then 20mL simulated intestinal fluid (mixed pancreatin with 10 mmol/L bile salts and 100U/mL trypsin) was added, the intestinal digest was again adjusted to ph=7 with 5mol/L NaOH solution, and incubated 2h at 37 ℃,150 rpm;
Respectively collecting the digestive juice after the reaction in the oral cavity, stomach and small intestine digestion stage, and centrifuging (4 ℃ C., 12000 rpm,30 min) at low temperature to obtain supernatant mixed micelle;
After demulsification treatment of the mixed micelle with DMSO, measuring the curcumin content in the mixed micelle at 429 nm wavelengths by using a UV-vis spectrometer; the content corresponds to curcumin released from a sample to be tested after digestion, and the curcumin release rate can be further calculated by adopting the formula (1):
（1）
2. stability test of Cur-SACD/CS nanocarriers:
(1) Stability of Cur-SACD/CS nanocarriers in gastric acid environment:
adjusting the pH of 0.9% NaCl solution to be=2.0 by using 1 mol/L HCl solution, dispersing 10mg Cur-SACD/CS nano-carrier in the solution of 1 mL, incubating at 37 ℃ for 2h, centrifuging to remove supernatant, and collecting precipitate;
(2) Stability of Cur-SACD/CS nanocarriers in intestinal juice pH environment:
Adjusting the pH of 0.9% NaCl solution to be 7.0 by using 1 mol/L NaOH solution, dispersing 10 mg Cur-SACD/CS nano-carrier in the solution of 1 mL, incubating at 37 ℃ for 2h, centrifuging to remove supernatant, and collecting precipitate;
(3) Stability of Cur-SACD/CS nanocarriers under physiological ionic strength:
10 mg Cur-SACD/CS nano-carrier is weighed and dispersed in 1mL of 0.9% NaCl solution, and after incubation for 30min at room temperature, supernatant is removed by centrifugation, and sediment is collected;
(4) Stability of Cur-SACD/CS nanocarriers at physiological temperature: dispersing 10 mg Cur-SACD/CS nano-carrier in 1 mL 0.9% NaCl solution, incubating at 37 ℃ for 8: 8h, centrifuging to remove supernatant, and collecting precipitate;
under the above conditions, an aqueous dispersion of curcumin was used as a control;
the collected precipitate was extracted with 4 mL absolute ethanol, the residual curcumin was measured for absorbance at 429 nm wavelength, and the curcumin Retention (RI) in the Cur-SACD/CS nanocarrier was calculated using formula (2):
（2）
3. Loading curve of SACD/CS nanoparticles against curcumin:
To obtain loading curves of curcumin in nanoparticles, samples were taken as the loading process proceeded to 10 min, 20 min, 30min, 40 min, 50 min, 60 min, 90 min, 120 min, 180 min and 240 min, respectively;
Measuring absorbance of curcumin in supernatant fluid at 429 nm wavelength by adopting a UV-vis spectrometer, calculating curcumin content in the Cur-SACD/CS nano-carrier, and further respectively calculating curcumin loading capacity (LA) and loading rate (LE) of the Cur-SACD/CS nano-carrier according to a formula (3) and a formula (4):
（3）
（4）
the starting materials used in the examples and comparative examples:
the preparation method of succinic acid cyclodextrin ester (SACD) comprises the following steps:
Fully dissolving 4 g beta-cyclodextrin, 2.96 g succinic acid and 4 g sodium hypophosphite in 40 mL deionized water to prepare a mixed solution; pouring the mixed solution into a glass plate with the diameter of 160 mm, and placing the glass plate in a 100 ℃ oven for drying 4 h; transferring the dried mixture into a 140 ℃ oven to start dry-thermal esterification reaction 20 min, taking out a plate and cooling to room temperature; subsequently dissolving the crude product in the dish with deionized water, separating the precipitated SACD with absolute ethanol, and washing with absolute ethanol for 3 times to remove residual impurities; fully drying the purified SACD at 50 ℃ for 8 h to be used; the substitution degree of the prepared SACD is 3.20 through testing;
Chitosan CS: medium viscosity, 200-400 mPa.s;
curcumin: the purity is more than or equal to 65%;
The percentages mentioned in the examples and comparative examples are not specified in mass percent; the reaction temperature is not specifically indicated and is referred to as normal temperature reaction; the solvent is not specifically indicated and water is used as the solvent.
Example 1
A method for preparing a controlled release nanocarrier Cur-SACD/CS that improves the bioavailability of curcumin, comprising the steps of:
(1) Preparation of SACD/CS nanoparticles:
Dissolving 1 g CS in a glacial acetic acid solution with the mass fraction of 1% of 100 mL, and adjusting the pH value to be 5.3 by using a 0.2 mol/L NaOH solution after the glacial acetic acid solution is fully dissolved to obtain a CS solution;
1 g SACD was dissolved in 100mL pH =5.3 acetic acid-sodium acetate buffer to give SACD solution;
Slowly adding the SACD solution into (50 mL/min) CS solution, and stirring 400: 400 rpm to react for 20min; slowly dripping (3 mL/min) 400 mL absolute ethanol, and continuously stirring 400 rpm for 1 h to promote particle formation; after the reaction is finished, centrifugally collecting SACD/CS nano-particles in the solution, washing 3 times by using an ethanol water solution with the volume fraction of 67%, and drying to obtain the SACD/CS nano-particles;
(2) SACD/CS nanoparticle loading curcumin:
dispersing 0.5 g SACD/CS nano-particles in 45 mL water, and continuously stirring 150 rpm for 30 min to hydrate to obtain SACD/CS nano-particle suspension;
dispersing curcumin in absolute ethyl alcohol to obtain curcumin solution with concentration of 1 mg/mL;
Adding 0.5 mL curcumin solution into 45 mLSACD/CS nanoparticle suspension, and carrying out light-shielding and 300 rpm stirring reaction for 3h to realize loading of curcumin; after the reaction is finished, centrifugally collecting Cur-SACD/CS nano-carriers in the solution, and drying to obtain the nano-carriers Cur-SACD/CS (SACD: CS=5:5).
Example 2
The amount of SACD used in step (1) of example 1 was adjusted to 1.4g, and the procedure was otherwise identical to that of example 1, to obtain nano-carrier Cur-SACD/CS (SACD: CS=7:5).
Example 3
The amount of SACD used in step (1) of example 1 was adjusted to 1.8g, and the procedure was otherwise identical to that of example 1, to obtain nano-carrier Cur-SACD/CS (SACD: CS=9:5).
Comparative example 1
SACD in step (1) of example 1 was omitted, and the adjustment step (1) was:
1g CS is dissolved in 1% glacial acetic acid solution of 100 mL, and after the solution is fully dissolved, the pH value of the solution is regulated to be 5.3 by using 0.2 mol/L NaOH solution, so that CS solution is obtained;
Slowly dripping (3 mL/min) 400 mL absolute ethyl alcohol into the CS solution, and continuously stirring 400 rpm for 1 h; centrifuging to collect precipitate in the solution, washing with 67% ethanol water solution for 3 times, and drying to obtain CS nanoparticles;
The procedure was otherwise as in example 1 to give Cur-CS vector.
Comparative example 2
The amount of SACD used in step (1) of example 1 was adjusted to 0.2 g, and the procedure was otherwise consistent with example 1 to give nanocarriers Cur-SACD/CS (SACD: CS=1:5).
Comparative example 3
The amount of SACD used in step (1) of example 1 was adjusted to 0.6 g, and the procedure was otherwise consistent with example 1 to give nanocarriers Cur-SACD/CS (SACD: CS=3:5).
The nanocarriers prepared in examples 1 to 3 and comparative examples 1 to 3 were subjected to performance test, and the test results were as follows:
FIG. 1 is an SEM image of SACD/CS complexes prepared in examples 1-3 and comparative examples 1-3, wherein (a) comparative example 1 (0:5); (b) comparative example 2 (1:5); (c) comparative example 3 (3:5); (d) example 1 (5:5); (e) example 2 (7:5); (f) example 3 (9:5). As can be seen from fig. 1: the SACD/CS nanoparticle prepared in example 1 has uniform microscopic morphology; the SACD/CS nanoparticles prepared in examples 2,3 exhibit a coherent nanoparticle aggregate structure; CS in comparative example 1 exhibited an irregular network structure, with no nanoparticle structure present; in comparative example 2, only a small amount of nanoparticle structure was present in SACD/CS, and the remaining majority exhibited a slightly crosslinked network structure; in comparative example 3, SACD/CS had a large number of nanoparticle structures, but there was still a partially crosslinked network structure between the nanoparticles.
FIG. 2 is a FTIR spectrum of SACD/CS complexes prepared in examples 1-3 and comparative examples 2-3. As can be seen from fig. 2: the characteristic peak associated with the N-H bending vibration of the primary amine group in example 1 red shifted from 1589 cm -1 to 1579 cm -1, a phenomenon that demonstrates that the amino groups of CS crosslink with SACD by electrostatic interaction to form composite nanoparticles; the characteristic peak associated with the N-H bending vibration of the primary amine group in example 2 (1589 cm -1) red shifted from 1589 cm -1 to 1579 cm -1, with SACD: cs=5: 5 (example 1) no further red shift was observed compared to the SACD/CS complex prepared, indicating that the electrostatic interaction between SACD and CS has reached saturation; characteristic peaks (1589 cm -1) associated with the N-H bending vibration of the primary amine group in 3 were implemented to red shift from 1589 cm -1 to 1579 cm -1, and SACD: cs=5: 5 (example 1) no further red shift was observed compared to the SACD/CS complex prepared, indicating that the electrostatic interaction between SACD and CS has reached saturation; the characteristic peak (1589 cm -1) related to the N-H bending vibration of the primary amine group in comparative example 2 cannot be observed to significantly move, which indicates that the electrostatic interaction between the amino group of CS and SACD is weak, and the requirement of forming composite nanoparticles cannot be fully satisfied; the characteristic peak associated with the N-H bending vibration of the primary amine group in comparative example 3 was red-shifted from 1589 cm -1 to 1583 cm -1, which demonstrates that the amino group of CS and SACD are crosslinked by electrostatic interaction to form a nanoparticle structure, which is still incomplete compared with example 1.
FIG. 3 shows the release of curcumin at various stages of in vitro simulated digestion of the nanocarriers prepared in examples 1-3 and comparative examples 1-3. As can be seen from fig. 3: the nano-carriers prepared in the embodiments 1,2 and 3 enable more curcumin to be dispersed into digestive juice and be absorbed and utilized by intestinal epithelial cells, and the accumulated release rates of the curcumin in the upper digestive tract reach 75.19%, 73.25% and 74.20%, so that the delayed control delivery of the curcumin in the digestion process is realized, and the nano-carriers have great application potential in the health fields such as foods, medicines and the like; comparative example 1 in the in vitro simulated digestion process, the release rates of curcumin in Cur-CS carrier in oral cavity, stomach and small intestine digestive juice are 0.02%, 0.03% and 8.46%, respectively, which are not significantly different from the release rates of non-loaded curcumin (0.03%, 0.07% and 7.94%), the cumulative release rate of curcumin in upper digestive tract is only 8.51%, which is not advantageous compared with the prior art; comparative example 2 in the in vitro simulated digestion process, the release rates of curcumin in Cur-SACD/CS nanocarriers in oral, gastric and small intestine digestive juice were 0.04%, 0.45% and 12.69%, respectively, and there was no significant difference in the release rates of curcumin without loading (0.03%, 0.07% and 7.94%), the cumulative release rate of curcumin in the upper digestive tract was only 13.18%, which is not advantageous over the prior art; comparative example 3 in the in vitro simulated digestion process, the release rates of curcumin in Cur-SACD/CS nano-carriers in oral, gastric and small intestine digestive juice were 3.56%, 9.88% and 19.64%, respectively, and compared with the release rates of non-loaded curcumin (0.03%, 0.07% and 7.94%), the prepared Cur-SACD/CS nano-carriers dispersed more curcumin into digestive juice and could be absorbed and utilized by intestinal epithelial cells, but the cumulative release rate of curcumin in upper digestive tract was only 33.08%, which is not advantageous compared with the prior art.
FIG. 4 shows the retention rate of curcumin in Cur-SACD/CS nanocarriers prepared in example 1 after incubation at simulated gastric fluid pH (a), intestinal fluid pH (b), physiological salt concentration (c) and physiological temperature (d) (I-VI show that the difference between samples is significant, and p < 0.05). As can be seen from fig. 4: after curcumin in the Cur-SACD/CS carrier is treated by 2 h, 12 h, 12 h and 12 h under the conditions of simulated gastric fluid pH, intestinal fluid pH, physiological salt concentration and physiological temperature, the retention rate is changed from 88%, 24%, 35% and 19% to 88%, 72%, 70% and 63% respectively, which shows that the stability of the curcumin is obviously improved.
Fig. 5 is a loading curve of curcumin for the nanocarriers prepared in example 1 and comparative example 1. As can be seen from fig. 5: the loading capacity of SACD/CS to curcumin reaches 0.36 mg/g, the loading rate is 36%, and the loading effect of CS to curcumin is far higher.
Comparative example 4
The chitosan in the step (1) of the adjustment example is guar hydroxypropyl trimethyl ammonium chloride (GHC) (synthetic cationic polysaccharide, similar to chitosan), and is specifically as follows:
1g of GHC was dissolved in 100 mL pH.3 acetic acid-sodium acetate buffer to give GHC solution;
1 g SACD was dissolved in 100mL pH =5.3 acetic acid-sodium acetate buffer to give SACD solution;
Slowly adding the SACD solution into (50 mL/min) GHC solution, and stirring 400: 400 rpm to react for 20min; slowly dripping (3 mL/min) 400 mL absolute ethanol, and continuously stirring 400 rpm for 1 h to promote complex formation; after the reaction is finished, centrifugally collecting SACD/GHC compound in the solution, washing 3 times by using ethanol water solution with the volume fraction of 67%, and drying to obtain SACD/GHC compound (the morphology is shown in figure 6);
The others remain the same as in example 1.
The result shows that: although some sites of the SACD/GHC complex were observed to have nanoparticle-like structures, the inter-particle adhesion was severe, and the rest of the sites failed to observe the particle structure, but rather a flaky, smooth polymer morphology (FIG. 6). When SACD/GHC is dispersed in water for loading curcumin, the SACD/GHC complex gradually dissolves, cannot be used for loading curcumin, and cannot be further explored for its controlled release effect during digestion in vitro.
Comparative example 5
The chitosan in the step (1) of the embodiment is adjusted to be Arabic gum, and the method is as follows:
1g of gum arabic is dissolved in 100 mL pH =5.3 acetic acid-sodium acetate buffer to obtain a gum arabic solution;
1 g SACD was dissolved in 100mL pH =5.3 acetic acid-sodium acetate buffer to give SACD solution;
Slowly adding the SACD solution into the (50 mL/min) Arabic gum solution, and stirring 400: 400 rpm to react 20: 20 min; slowly dripping (3 mL/min) 400 mL absolute ethanol, and continuously stirring 400 rpm for 1h to promote complex formation; after the reaction is finished, centrifugally collecting SACD/Arabic gum complex in the solution, washing 3 times by using ethanol water solution with the volume fraction of 67%, and drying to obtain SACD/Arabic gum complex;
The others remain the same as in example 1.
The result shows that: when the SACD/acacia complex carrier is dispersed in water for loading curcumin, the SACD/acacia complex is gradually dissolved, cannot be used for loading curcumin, and cannot be further explored for its controlled release effect during in vitro digestion.
Comparative example 6
The chitosan in the step (1) of the embodiment is adjusted to be gelatin, and the method is as follows:
1 g gelatin was dissolved in 100 mL pH =5.3 acetic acid-sodium acetate buffer to give gelatin solution;
1 g SACD was dissolved in 100mL pH =5.3 acetic acid-sodium acetate buffer to give SACD solution;
Slowly adding the SACD solution into (50 mL/min) gelatin solution, and stirring 400: 400 rpm to react 20: 20 min; slowly dripping (3 mL/min) 400 mL absolute ethanol, and continuously stirring 400 rpm for 1h to promote complex formation; after the reaction is finished, centrifugally collecting SACD/gelatin complex in the solution, washing 3 times by using ethanol water solution with the volume fraction of 67%, and drying to obtain SACD/gelatin complex;
The others remain the same as in example 1.
The result shows that: when the SACD/gelatin complex carrier is dispersed in water for loading curcumin, the SACD/gelatin complex is gradually dissolved, cannot be used for loading curcumin, and cannot be further explored for the controlled release effect during in vitro digestion.
Comparative example 7
The CS in step (1) of example 1 was omitted, specifically as follows:
Weighing 0.5 g SACD into 45: 45 mL water, and continuously stirring at 150: 150 rpm for 30: 30min to obtain SACD solution;
dispersing curcumin in absolute ethyl alcohol to obtain curcumin solution with concentration of 1 mg/mL;
0.5mL of curcumin solution is added into 45 mL SACD solution to avoid light, and 300: 300 rpm is stirred for reaction.
The result shows that: because SACD has extremely strong water solubility, curcumin is in a completely dissolved state after being loaded in the SACD, and the release effect of the curcumin in the in-vitro digestion process cannot be further explored.
Comparative example 8
The SACD of example 1 was modified to be the cyclodextrin derivative octenyl succinate cyclodextrin ester (OSACD) (having a similar branching group as SACD and expected to be used in food);
the preparation method of the cyclodextrin derivative octenyl succinic acid cyclodextrin ester (OSACD) comprises the following steps:
dissolving beta-cyclodextrin into water to make the mass fraction of the beta-cyclodextrin be 10%, and stirring the beta-cyclodextrin at 50 ℃ and 300 rpm for 2 h; then, an ethanol dilution (4-fold dilution) of octenyl succinic anhydride was added dropwise to the solution, the process was completed within 2h, and the reaction system ph=8.5 was controlled with a 3% NaOH solution; after the pH value of the system is constant, 3% hydrochloric acid solution is used for adjusting the pH value of the reaction system to 6.5; drying the obtained mixture, then fully washing with ethanol, and drying again to obtain a product OSACD;
The others remain the same as in example 1.
The result shows that: OSACD cannot form a complex with CS, cannot be used to load curcumin, nor can it be further explored for their controlled release effect during digestion in vitro.
Comparative example 9
The curcumin loading step in example 1 was adjusted to synchronize encapsulation during nanoparticle formation, as follows:
1 g CS was dissolved in 100 mL pH =5.3 acetic acid-sodium acetate buffer to give CS solution;
1 g SACD was dissolved in 100mL pH =5.3 acetic acid-sodium acetate buffer to give SACD solution;
dispersing curcumin in absolute ethyl alcohol to obtain curcumin solution with concentration of 1 mg/mL;
Slowly adding the SACD solution into (50 mL/min) CS solution, and stirring 400/rpm to react 20/min to obtain SACD/CS self-assembly solution;
Adding 0.5 mL curcumin solution into 400 mL absolute ethanol, slowly dripping (3 mL/min) the curcumin-containing ethanol solution into SACD/CS self-assembly solution, and continuing stirring with 400 rpm for 1h to promote particle formation; after the reaction, centrifugally collecting the Cur-SACD/CS nano-carriers in the solution, washing the Cur-SACD/CS nano-carriers with an ethanol water solution with the volume fraction of 67% for 3 times, and drying the washed Cur-SACD/CS nano-carriers to obtain the Cur-SACD/CS nano-carriers (SACD: CS=5:5).
The result shows that: the loading rate of curcumin loaded in SACD/CS nano-carrier by adopting the synchronous encapsulation method is only about 3%, which proves that the synchronous encapsulation method is not suitable for loading curcumin in SACD/CS nano-particles.
While the invention has been described with reference to the preferred embodiments, it is not limited thereto, and various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (6)
1. A method for preparing a controlled release nanocarrier Cur-SACD/CS that enhances the bioavailability of curcumin, comprising the steps of:
(1) Preparation of SACD/CS nanoparticles:
Slowly adding the cyclodextrin succinate SACD solution into the chitosan CS solution, and stirring for reaction; slowly dripping ethanol, continuously stirring to promote particle formation, and after the reaction is finished, carrying out solid-liquid separation, washing and drying to obtain SACD/CS nano particles; wherein, the mass ratio of SACD in SACD solution to CS in CS solution is 1:1, a step of;
(2) SACD/CS nanoparticle loading curcumin:
Dispersing SACD/CS nano-particles in water, and hydrating to obtain SACD/CS nano-particle suspension; adding the curcumin solution into the SACD/CS nanoparticle suspension, and stirring for reaction in a dark place; after the reaction is finished, carrying out solid-liquid separation and drying to obtain a nano carrier Cur-SACD/CS;
wherein the SACD/CS nanoparticle suspension comprises SACD/CS nanoparticle and water in an amount ratio of 0.5 g:40-100 mL;
The volume ratio of curcumin solution to SACD/CS nanoparticle suspension was 0.5:40-100;
The concentration of curcumin solution is 0.5-5 mg/mL.
2. The method of claim 1, wherein the concentration of SACD solution in step (1) is 0.001-10 g/mL.
3. The method according to claim 1, wherein the CS solution in step (1) is prepared by: dissolving CS in glacial acetic acid solution, and then adopting sodium hydroxide solution to adjust the pH value to 5.3; wherein, the dosage ratio of CS to glacial acetic acid solution is 0.1-2 g:100 And (3) mL.
4. The method of claim 1, wherein the ethanol in step (1) is absolute ethanol.
5. The nano-carrier Cur-SACD/CS prepared by the method of any one of claims 1-4.
6. The use of the nanocarrier Cur-SACD/CS of claim 5 for the preparation of a food or pharmaceutical product.
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