CN111346056B - Preparation method of alpha-glucosyl hesperidin modified lutein liposome - Google Patents
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Abstract
The invention discloses a preparation method of an alpha-glucosyl hesperidin modified lutein liposome. The lutein liposome provided by the invention is obtained by modifying alpha-glucosyl hesperidin, and the specific method comprises the following steps: (1) dissolving lutein and lipid material to obtain lutein lipid solution; (2) hydrating the lipid membrane, and performing ultrasonic treatment to obtain a dispersion liquid; (3) dripping the alpha-glucosyl hesperidin solution into the dispersion liquid, and stirring at room temperature overnight; (4) and extruding the dispersion liquid through a polycarbonate membrane to obtain the lutein liposome. The lutein liposome modified by the alpha-glucosyl hesperidin has the properties of high stability and long-acting circulation, and the absorption of the lutein in eyes is obviously improved.
Description
One, the technical field
The invention belongs to the technical field of functional food processing, and particularly relates to a preparation method of an alpha-glucosyl hesperidin modified lutein liposome.
Second, background Art
Lutein, a natural carotenoid widely found in vegetables, fruits, flowers and certain algae organisms, is not synthesized by the human body itself and must be ingested or supplemented from the diet. Lutein is one of the main components of macular pigment of eyes, has the functions of absorbing blue light and enhancing retina tissues, and has obvious effects on the aspects of protecting vision, preventing cataract and the like. However, the molecular structure of lutein has a long carbon chain and contains a plurality of hydrophobic groups, so that the lutein has poor solubility in water, and the application of lutein in the fields of food, medicines and the like is limited.
The lutein is embedded in the forms of microcapsule technology, nano self-emulsifying carrier, nano-emulsifying composite system, liposome and the like, and is an effective means for improving the solubility, the tolerance to the external environment and the bioavailability. The lutein is embedded in the form of liposome, the preparation process is simple, and the lutein has higher loading capacity and encapsulation efficiency. The liposome is mainly phagocytized by a reticuloendothelial system after being loaded with drugs to activate the autoimmune function of a body, but the liposome is easy to be eliminated by a mononuclear macrophage system and the reticuloendothelial system in the body because the structure of the liposome membrane is similar to a biological membrane. It has been found that the stability of liposomes in blood can be increased by attaching a polyhydroxy group-containing substance to the phospholipid molecule, exposing some hydrophilic polysaccharides or polyhydroxy groups on the liposome surface. When the two factors of steric hindrance and increasing the hydrophilicity of the membrane surface act together, the liposome forms a long-acting liposome. In the existing research, polyethylene glycol (PEG) polymers with hydrophilicity and flexibility are often adopted to modify the surface of liposome, so that the adsorption of plasma components and the surface of the liposome is hindered, and the time of the liposome in systemic circulation is prolonged. For example, chinese patent CN101843584B discloses a compound of all-trans retinoic acid and liposome and its application, and the compound has better stability in serum system. However, after long-term use of the liposome modified by PEG, human bodies can generate anti-PEG IgG, and the immunogenicity of PEG can cause obvious humoral immune reaction, so that the blood half-life of the liposome modified by PEG is obviously shortened. Therefore, a substitute of PEG which can be circulated for a long time and is safe and nontoxic is searched, and the targeting location and the biological value of the liposome are effectively improved.
The lutein liposome is modified by the alpha-glucosyl hesperidin, the surface of the lutein liposome is coated with the alpha-glucosyl hesperidin through self-assembly, the hydrophobic head of the alpha-glucosyl hesperidin is positioned at the head of the liposome, and the hydrophilic terminal glucoside group is exposed on the surface of the liposome. The prepared alpha-glucosyl hesperidin-lutein liposome is safe and nontoxic, has high stability and long-acting circulation performance, and is beneficial to improving the in-vivo and in-vitro stability of the lutein liposome, prolonging the in-vivo circulation time, reducing the accumulation of lutein in the liver and the spleen, and remarkably improving the absorption of the lutein in the eyes.
Third, the invention
The invention aims to provide a preparation method of an alpha-glucosyl hesperidin modified lutein liposome, and the lutein liposome prepared by the method has good stability, long-acting circulation and high biological safety.
In order to achieve the purpose, the invention adopts the technical scheme that:
(1) dissolving lutein and lipid phase in chloroform-methanol solution at volume ratio of 2: 1 to obtain lutein lipid solution.
(2) Rotary evaporation is carried out to remove the organic solvent, so that the compound forms a uniform film at the bottom of the round-bottom flask, the vacuum degree is increased to 0.1MPa, and continuous pumping is carried out for 30 min.
(3) Adding phosphate solution into the composite film obtained in the step (2) for hydration, wherein the hydration temperature is 40-60 ℃, and the time is 30-120 min;
(5) carrying out ultrasonic treatment under the ice-water bath stirring condition, wherein the ultrasonic power is 800W, the pulse is 5s/5s, the treatment time is 10-30 min, then continuously stirring for 3-6 h at the temperature of 30-40 ℃, and the stirring rotating speed is 800-1200 r/min;
(6) centrifuging the dispersion obtained in the step (5) for 10min at the speed of 10000r/min, and removing the non-embedded lutein;
(7) dissolving alpha-glucosyl hesperidin in a phosphate solution to obtain an alpha-glucosyl hesperidin solution with the mass concentration of 0.5-10%, dropwise adding the alpha-glucosyl hesperidin solution into the dispersion liquid obtained in the step (6), and stirring at room temperature overnight;
(8) extruding the dispersion liquid obtained in the step (7) for 10-20 times through a 200nm polycarbonate membrane, and removing excessive alpha-glucosyl hesperidin through a G200 sephadex column to obtain the alpha-glucosyl hesperidin-lutein liposome.
Preferably, in the step (1), the lipid phase consists of cholesterol and dipalmitoylphosphatidylcholine, the mass ratio of the cholesterol to the dipalmitoylphosphatidylcholine is 0.1-0.5, the concentration of lutein in the lutein lipid solution is 0.1-2.0%, and the mass ratio of lutein to the lipid phase is 0.1-0.5 mg/100 mg.
Preferably, the volume ratio of the lutein solution to the alpha-glucosyl hesperidin solution in the step (7) is 1: 2-1: 10, the dropping speed is 10-30 drops per minute, and the stirring speed is 100-700 r/min.
Compared with the prior art, the invention has the following beneficial effects:
(1) the liposome takes cholesterol and dipalmitoyl phosphatidylcholine as wall materials, is an ideal carrier for embedding lutein, and has high lutein encapsulation rate (more than or equal to 90 percent);
(2) the alpha-glucosyl hesperidin modifies the lutein liposome to form a dense protective layer on the surface of the liposome, so that the shrinkage and aggregation of the liposome are effectively avoided through the steric hindrance effect, the distribution uniformity of the liposome is improved, and the in-vivo and in-vitro stability of the liposome is improved;
(3) the alpha-glucosyl hesperidin is coated on the surface of the lutein liposome through self-assembly, the hydrophobic head of the alpha-glucosyl hesperidin is positioned at the head of the liposome, and the hydrophilic end glycoside group is exposed on the surface of the liposome, so that the slow release performance of the lutein liposome is improved, the accumulation of lutein in the liver and the spleen is reduced, and the absorption of the lutein in the eyes is obviously improved.
(4) The invention adopts a film dispersion method to prepare the liposome, the probe type intermittent ultrasonic treatment forms small single-chamber liposome, and the lutein liposome is obtained after the extrusion of polycarbonate film, the average grain diameter is less than 200nm, and the storage stability is high.
Drawings
FIG. 1 in vitro release curve of alpha-glucosyl hesperidin modified lutein liposome
Detailed Description
The following examples are intended to describe the invention in further detail, but are not intended to limit the invention in any way.
Example 1
Dissolving lutein, cholesterol and dipalmitoylphosphatidylcholine in a volume ratio of 2: 1 to obtain a solution containing 0.1% lutein ester. Rotary evaporation is carried out to remove the organic solvent, so that the compound forms a uniform film at the bottom of the round-bottom flask, the vacuum degree is increased to 0.1MPa, and continuous pumping is carried out for 30 min. Adding phosphate solution into the composite film for hydration at 60 ℃ for 120 min; carrying out ultrasonic treatment under the condition of ice-water bath stirring, wherein the ultrasonic power is 800W, the pulse is 5s/5s, the treatment time is 20min, and then continuously stirring for 3h at the temperature of 30 ℃, and the stirring speed is 1000 r/min; centrifuging the dispersion at 10000r/min for 10min to remove non-embedded xanthophyll. The dispersion was added dropwise with an alpha-glucosyl hesperidin solution (0.5%) and stirred at room temperature overnight. Extruding the obtained dispersion liquid for 10 times by a polycarbonate membrane with the thickness of 200nm, removing excessive alpha-glucosyl hesperidin by a G200 sephadex column to obtain the alpha-glucosyl hesperidin-lutein liposome.
Control group: dissolving lutein, cholesterol and dipalmitoylphosphatidylcholine in chloroform-methanol solution at volume ratio of 2: 1 to obtain 0.1% lutein ester solution. Rotary evaporation is carried out to remove the organic solvent, so that the compound forms a uniform film at the bottom of the round-bottom flask, the vacuum degree is increased to 0.1MPa, and continuous pumping is carried out for 30 min. Adding phosphate solution into the composite film for hydration at 60 ℃ for 120 min; carrying out ultrasonic treatment under the condition of ice-water bath stirring, wherein the ultrasonic power is 800W, the pulse is 5s/5s, the treatment time is 20min, and then continuously stirring for 3h at the temperature of 30 ℃, and the stirring speed is 1000 r/min; centrifuging the dispersion at 10000r/min for 10min to remove non-embedded xanthophyll. Extruding the obtained dispersion liquid with 200nm polycarbonate membrane for 10 times, removing excessive alpha-glucosyl hesperidin by G200 sephadex column to obtain common xanthophyll liposome as control group.
The control group and the experimental group are subjected to in-vitro simulated gastric and intestinal digestion experiments, and research results show that when the lutein content is 0.1%, the release rate of the lutein in the control group in gastric juice is higher than 30%, and the release rate of the lutein in intestinal juice is higher than 20%. The release rate of lutein in gastric juice is lower than 25% and the release rate in intestinal juice is lower than 15%. The lutein liposome obtained from the control group and the experimental group is respectively subjected to intragastric lavage treatment on C57BL/6 mice. Lutein in eyes, livers and spleens of mice after 10h of gastric lavage treatment is extracted, and high performance liquid chromatography detection shows that the content of lutein in eye plasma of the mice in an experimental group is obviously higher than that of lutein in eye plasma of a control group. The research also finds that the elimination half-life period of the lutein liposome in the experimental group in the mouse body is obviously prolonged compared with that of the lutein liposome in the control group.
Example 2
Dissolving lutein, cholesterol and dipalmitoylphosphatidylcholine in chloroform-methanol solution at volume ratio of 2: 1 to obtain 2% lutein ester solution. Rotary evaporation is carried out to remove the organic solvent, so that the compound forms a uniform film at the bottom of the round-bottom flask, the vacuum degree is increased to 0.1MPa, and continuous pumping is carried out for 30 min. Adding phosphate solution into the composite film for hydration at 55 ℃ for 100 min; carrying out ultrasonic treatment under the condition of ice-water bath stirring, wherein the ultrasonic power is 800W, the pulse is 5s/5s, the treatment time is 30min, and then continuously stirring for 3h at the temperature of 40 ℃, and the stirring speed is 1000 r/min; centrifuging the dispersion at 10000r/min for 10min to remove non-embedded xanthophyll. The dispersion was added dropwise with an alpha-glucosyl hesperidin solution (10%) and stirred at room temperature overnight. Extruding the obtained dispersion liquid for 20 times through a polycarbonate membrane with the thickness of 200nm, removing excessive alpha-glucosyl hesperidin by using a G200 sephadex column to obtain the alpha-glucosyl hesperidin-lutein liposome.
Control group: dissolving lutein, cholesterol and dipalmitoylphosphatidylcholine in chloroform-methanol solution at volume ratio of 2: 1 to obtain 2% lutein ester solution. Rotary evaporation is carried out to remove the organic solvent, so that the compound forms a uniform film at the bottom of the round-bottom flask, the vacuum degree is increased to 0.1MPa, and continuous pumping is carried out for 30 min. Adding phosphate solution into the composite film for hydration at 55 ℃ for 100 min; carrying out ultrasonic treatment under the condition of ice-water bath stirring, wherein the ultrasonic power is 800W, the pulse is 5s/5s, the treatment time is 30min, and then continuously stirring for 3h at the temperature of 40 ℃, and the stirring speed is 1000 r/min; centrifuging the dispersion at 10000r/min for 10min to remove un-embedded xanthophyll, extruding the obtained dispersion with 200nm polycarbonate membrane for 10 times, and removing excessive alpha-glucosyl hesperidin with G200 Sephadex column to obtain common xanthophyll liposome as control group.
The average particle size of the experiment group liposome is smaller than that of the control group, and the polydispersity index PDI value of the experiment group liposome is smaller than that of the control group, which indicates that the lutein liposome modified by the alpha-glucosyl hesperidin has good dispersibility. The experimental group and the control group are respectively stored for 7 days under normal temperature conditions, and the lutein retention rate of the experimental group is obviously higher than that of the control group.
Claims (3)
1. A preparation method of an alpha-glucosyl hesperidin modified lutein liposome is characterized by comprising the following steps:
(1) dissolving lutein and lipid phase in chloroform-methanol solution at volume ratio of 2: 1 to obtain lutein lipid solution;
(2) rotary evaporating to remove organic solvent, allowing the compound to form a uniform film at the bottom of the round-bottom flask, increasing the vacuum degree to 0.1MPa, and continuously pumping for 30 min;
(3) adding phosphate solution into the composite film obtained in the step (2) for hydration, wherein the hydration temperature is 40-60 ℃, and the time is 30-120 min;
(5) carrying out ultrasonic treatment under the ice-water bath stirring condition, wherein the ultrasonic power is 800W, the pulse is 5s/5s, the treatment time is 10-30 min, then continuously stirring for 3-6 h at the temperature of 30-40 ℃, and the stirring rotating speed is 800-1200 r/min;
(6) centrifuging the dispersion obtained in the step (5) for 10min at the speed of 10000r/min, and removing the non-embedded lutein;
(7) dissolving alpha-glucosyl hesperidin in a phosphate solution to obtain an alpha-glucosyl hesperidin solution with the mass concentration of 0.5-10%, dropwise adding the alpha-glucosyl hesperidin solution into the dispersion liquid obtained in the step (6), and stirring at room temperature overnight;
(8) extruding the dispersion liquid obtained in the step (7) for 10-20 times through a 200nm polycarbonate membrane, and removing excessive alpha-glucosyl hesperidin through a G200 sephadex column to obtain the alpha-glucosyl hesperidin-lutein liposome.
2. The preparation method of the alpha-glucosyl hesperidin-modified lutein liposome according to claim 1, is characterized in that: the lipid phase in the step (1) consists of cholesterol and dipalmitoylphosphatidylcholine, the mass ratio of the cholesterol to the dipalmitoylphosphatidylcholine is 0.1-0.5, the concentration of lutein in the lutein lipid solution is 0.1-2.0%, and the mass ratio of the lutein to the lipid phase is 0.1-0.5 mg/100 mg.
3. The preparation method of the alpha-glucosyl hesperidin-modified lutein liposome according to claim 1, is characterized in that: the volume ratio of the lutein to the alpha-glucosyl hesperidin in the step (7) is 1: 2-1: 10, the dripping speed is 10-30 drops per minute, and the stirring speed is 100-700 r/min.
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| CN114947126A (en) * | 2020-12-15 | 2022-08-30 | 江苏省农业科学院 | Method for improving bioavailability of beta-carotene by modifying hesperidin |
| CN114303915B (en) * | 2021-12-28 | 2023-04-21 | 华南理工大学 | Method for ultrasonically improving accumulation of carotenoid and lutein in corn sprouts |
Citations (3)
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| US7446101B1 (en) * | 2003-12-12 | 2008-11-04 | Bioactives, Llc | Bioavailable carotenoid-cyclodextrin formulations for soft-gels and other encapsulation systems |
| WO2016100972A2 (en) * | 2014-12-19 | 2016-06-23 | Kemin Industries, Inc. | Intraocular delivery of bioactive molecules using iontophoresis |
| CN105726482A (en) * | 2016-01-27 | 2016-07-06 | 江苏省农业科学院 | Xanthophyll nano-liposome and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7446101B1 (en) * | 2003-12-12 | 2008-11-04 | Bioactives, Llc | Bioavailable carotenoid-cyclodextrin formulations for soft-gels and other encapsulation systems |
| WO2016100972A2 (en) * | 2014-12-19 | 2016-06-23 | Kemin Industries, Inc. | Intraocular delivery of bioactive molecules using iontophoresis |
| CN105726482A (en) * | 2016-01-27 | 2016-07-06 | 江苏省农业科学院 | Xanthophyll nano-liposome and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| Isolation of C-Glucosylflavone from Lemon Peel and Antioxidative Activity of Flavonoid Compounds in Lemon Fruit;Yoshiaki Miyake等;《JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY》;19971231;第45卷(第12期);全文 * |
| Prevention of rat liver fibrosis by selective targeting of hepatic stellate cells using hesperidin carriers;Mohamed A.Morsy等;《International Journal of Pharmaceutics》;20181003;第552卷(第1-2期);全文 * |
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