CN115350290A - Preparation method and application of resveratrol nanocrystalline liposome based on TPGS modification - Google Patents
Preparation method and application of resveratrol nanocrystalline liposome based on TPGS modification Download PDFInfo
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Abstract
The invention discloses a preparation method and application of a resveratrol nanocrystalline liposome based on TPGS modification, belonging to the technical field of medicines and comprising the following steps: s1: mixing resveratrol and a stabilizer, performing ultrasonic dispersion, adding zirconia beads, grinding under magnetic stirring, and absorbing the nano suspension after grinding to obtain a resveratrol nanocrystal solution; s2: dissolving soybean lecithin, cholesterol and TPGS with an organic solvent, evaporating the solution under reduced pressure to remove the organic solvent until a milky film is formed, adding the resveratrol nanocrystal solution and the buffer solution for ultrasonic hydration, and then performing ultrasonic treatment by using an ultrasonic probe to obtain the TPGS modified resveratrol nanocrystal liposome. According to the resveratrol nanocrystal liposome modified based on TPGS, the resveratrol nanocrystal is loaded on the TPGS modified liposome, and the TPGS can reduce the particle size of the liposome and increase the stability of the liposome, and can promote a drug to enter a tumor cell to inhibit the efflux of a P-glycoprotein (P-gp) mediated drug.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a preparation method and application of a resveratrol nanocrystalline liposome based on TPGS modification.
Background
Resveratrol (Res), also known as resveratrol (3, 4', 5-trihydroxy-1, 2-diphenylethylene), is a polyphenol compound with homology of medicine and food, and exists in various plants such as grapes, rhizoma et radix Veratri, cassia seed, giant knotweed rhizome, mulberry and the like. Res has strong biological activity and has pharmacological actions of resisting inflammation, bacteria, oxidation and tumor, protecting heart and blood vessels, and the like. However, resveratrol has low water solubility, unstable property, low in-vivo bioavailability and rapid metabolism, so that resveratrol is not enough to exert corresponding pharmacological activity. Therefore, how to improve the stability and bioavailability of resveratrol becomes a key for development and utilization.
The nano crystal technology is a special method for reducing the grain diameter of a medicament to a nano level (1-1000 nm) aiming at an insoluble medicament in recent years, and the medicament has small grain diameter, high medicament loading amount and large specific surface area after the nano technology is applied, and can effectively improve the solubility and the dissolution rate of the insoluble medicament. The methods for preparing nanocrystals are generally classified into top-down and bottom-up methods, and also into a method in which both techniques are combined.
Although the nanocrystal plays an important role in improving the oral bioavailability of a poorly soluble drug, the nanocrystal belongs to a thermodynamically unstable system, and in recent years, many researches are carried out to achieve the purposes of increasing the stability, prolonging the retention time of the drug in vivo or the like by modifying the surface of the nanocrystal.
Disclosure of Invention
The invention aims to provide a preparation method and application of a resveratrol nanocrystal liposome modified based on TPGS (tyrosine-serine), wherein the resveratrol nanocrystal is loaded on the TPGS modified liposome, and the TPGS can reduce the particle size of the liposome and increase the stability of the liposome, and can promote a drug to enter a tumor cell to inhibit the efflux of a P glycoprotein (P-gp) mediated drug.
The technical scheme adopted by the invention for solving the technical problems is as follows:
provides a preparation method of resveratrol nanocrystalline liposome based on TPGS modification, which comprises the following steps:
s1: mixing resveratrol and a stabilizer, performing ultrasonic dispersion, adding zirconia beads, grinding under magnetic stirring, and absorbing the nano suspension after grinding to obtain a resveratrol nanocrystal solution;
s2: dissolving soybean lecithin, cholesterol and TPGS with an organic solvent, evaporating the solution under reduced pressure to remove the organic solvent until a layer of milky white film is formed, adding the resveratrol nanocrystal solution and the buffer solution for ultrasonic hydration, and then performing ultrasonic treatment by using an ultrasonic probe to obtain the TPGS modified resveratrol nanocrystal liposome;
the stabilizer is sodium dodecyl sulfate, and the mass ratio of the resveratrol to the stabilizer is (2);
the mass ratio of the soybean lecithin, cholesterol and TPGS is (20);
the organic solvent is trichloroethane.
Vitamin E polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of vitamin E and is formed by the reaction of the carboxyl group of vitamin E succinate and the hydroxyl group of polyethylene glycol. Because the vitamin E lipophilic peptide contains both vitamin E lipophilic group and polyethylene glycol hydrophilic long chain, the vitamin E hydrophilic peptide has better surfactant property and water solubility, can obviously increase the absorption of insoluble drugs in gastrointestinal tracts, and improves the bioavailability.
Further, the buffer solution is a phosphate buffer solution, and the volume ratio of the resveratrol nanocrystal solution to the phosphate buffer solution is 1.
Further, the zirconia beads have a size of 0.5mm.
Furthermore, the rotating speed of magnetic stirring is 1500r/min, and the grinding time is 12h.
Further, the time of ultrasonic hydration is 30min.
Further, the power of the ultrasonic probe is 150W, the ultrasonic time is 10min, and the ultrasonic time is 8s, and the interval is 4s.
An application of resveratrol nanocrystalline liposome based on TPGS modification in preparing oral preparation.
Compared with the prior art, the invention has the beneficial effects that:
1. according to the TPGS modified resveratrol nanocrystal liposome, insoluble medicine resveratrol is prepared into resveratrol nanocrystals, so that the medicine solubility and dissolution rate can be improved, and the adopted micro medium grinding method technology is simple to operate, does not involve an organic solvent, does not need special equipment and is low in cost;
2. the TPGS modified resveratrol nanocrystal liposome can reduce the particle size of the liposome, improve the stability of the liposome, promote the transfer of the liposome, weaken the recognition and uptake of cells of a reticuloendothelial system, and prolong the action time of a medicament in vivo.
Drawings
Other features, objects and advantages of the present application will become more apparent upon reading of the following detailed description of non-limiting embodiments thereof, made with reference to the accompanying drawings in which:
figure 1 is a picture of resveratrol nanocrystal solution and freeze-dried powder.
Fig. 2 is a graph of particle size versus potential for resveratrol nanocrystals.
Fig. 3 is a transmission electron micrograph of resveratrol nanocrystals.
Fig. 4 is a scanning electron microscope image of resveratrol bulk drug and resveratrol nanocrystal.
FIG. 5 is a TPGS-lipo @ Res-NC map.
FIG. 6 is a graph of particle size versus potential for TPGS-lipo @ Res-NC.
FIG. 7 is a transmission electron micrograph of TPGS-lipo @ Res-NC.
FIG. 8 is a graph showing stability tests of Res-NC and TPGS-lipo @ Res-NC.
FIG. 9 is a graph of in vitro release experiments for Res drug substance, res-NC and TPGS-lipo @ Res-NC.
FIG. 10 is a graph showing the caco-2 cytotoxicity assay of TPGS-lipo @ Res-NC.
FIG. 11 is a graph showing the caco-2 cell uptake and cell localization experiments for C6@ Lipo, C6 and @ TPGS-Lipo.
Detailed Description
The present application will be described in further detail with reference to the following drawings and examples. It is to be understood that the specific embodiments described herein are merely illustrative of the invention and are not to be construed as limiting the invention. It should be noted that, for convenience of description, only the portions related to the present invention are shown in the drawings.
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present application will be described in detail below with reference to the accompanying drawings in conjunction with embodiments.
1. Preparation of TPGS liposome-encapsulated resveratrol nanocrystal oral preparation
1. Preparation of resveratrol nanocrystals (Res-NC)
The penicillin bottle is used as a grinding chamber, the magnetic stirrer is used as a power device, and the zirconia beads with the diameter of 0.5mm are used as grinding media. Adding a magnetic rotor into a clean penicillin bottle, weighing 20mgSDS (sodium dodecyl sulfate) into the penicillin bottle, adding 2ml of deionized water for ultrasonic dissolution, weighing 40mg of resveratrol, adding the resveratrol into the penicillin bottle for ultrasonic dispersion, then adding 5ml of zirconia beads, sealing, and then driving the zirconia beads to grind for 12 hours at the rotating speed of 1500r/min by a magnetic stirrer. And after grinding, absorbing the nano suspension into an EP tube by using an injector, taking 3ml of ionized water for washing in a penicillin bottle five times, and adding the washing liquid into the EP tube to obtain Res-NC.
And (5) carrying out freeze drying on Res-NC to obtain freeze-dried powder. Res-NC solution and lyophilized powder are shown in figure 1; the particle size and potential diagram is shown in figure 2; the transmission electron micrograph is shown in FIG. 3; scanning electron micrograph of resveratrol and nanocrystal is shown in FIG. 4. As can be seen from the figure, the particle size of the resveratrol nanocrystal prepared by the micromedium method is (138.0 ± 3.5) nm (n = 3), the PDI value is 0.232 ± 0.096 (n = 3), and the potential is-7.15 ± 0.02 (n = 3). The resveratrol drug and Res-NC were observed by SEM and then characterized by TEM. The two electron microscope characterization results show that the nanocrystals have relatively uniform particle size distribution. This is in substantial agreement with the results obtained by the granulometer.
2. Preparation of resveratrol nanocrystal liposome (TPGS-lipo @ Res-NC)
Preparing resveratrol nanocrystal liposome by a thin film dispersion method. Weighing soybean lecithin, cholesterol, TPGS (mass ratio of 20.
Putting the resveratrol nanocrystalline liposome into a freezing layer of a refrigerator at the temperature of-80 ℃ for pre-freezing, and transferring the resveratrol nanocrystalline liposome into a freeze dryer for freeze drying after pre-freezing for 12 hours to obtain freeze-dried powder for later use.
TPGS-Lipo @ Res-NC was diluted as appropriate, and the particle size (113. + -. 5.21) nm (n = 3), PDI (0.242. + -. 0.010), and potential (-3.43. + -. 1.48) mv were measured using a particle sizer, as shown in FIG. 6. The morphology of TPGS-lipo @ Res-NC was characterized by TEM (FIG. 7). TPGS-lipo @ Res-NC is spherical and has a size corresponding to the measured particle diameter.
2. Characterization of resveratrol nanocrystal liposomes (TPGS-lipo @ Res-NC)
1. Encapsulation efficiency determination of TPGS-lipo @ Res-NC
Demulsifying 1ml of prepared TPGS-lipo @ Res-NC with methanol, diluting to a required concentration, passing through a 0.22 mu m microporous filter membrane, measuring the absorbance at the wavelength of 356nm by an ultraviolet spectrophotometer, and calculating the encapsulation rate of the TPGS-lipo @ Res-NC according to a formula.
Encapsulation ratio (%) = (amount of drug encapsulated in the preparation/initial amount of drug added) × 100%.
3 sets of parallel verification tests were performed, and the test results are shown in table 1. Table 1 shows the results of the encapsulation efficiency verification test.
TABLE 1 encapsulation efficiency verification test results
The experimental result shows that when the mass ratio of the soybean lecithin to the cholesterol to the TPGS is 10.
2. Stability test of TPGS-lipo @ Res-NC
The stability test was conducted on TPGS-lipo @ Res-NC, and changes in particle size, polydispersity index (PDI), and Zate potential of TPGS-lipo @ Res-NC were measured periodically over 30 days. As shown in FIG. 8, the particle size, polydispersity index and potential of the preparation did not change significantly within 30 days, and the stability was good.
3. Res bulk drug, res-NC and TPGS-lipo @ Res-NC in vitro release experiments
The in vitro release of Res drug, res-NC and TPGS-lipo @ Res-NC in different media (phosphate buffered solution pH =7.4, solution pH =1.2HCl and double distilled water) was investigated using dialysis bag diffusion method. Res, res-NC and TPGS-lipo @ Res-NC dispersed in 5ml PBS containing 0.5% SDS. And placed in a dialysis bag with a molecular weight cut-off of 14000 Da. The volume of the release medium is 20mL, the rotating speed is 100r/min, and the temperature is kept at 37.0 +/-0.5 ℃.1mL aliquots were removed at predetermined time intervals from the release medium and an equal volume of PBS and 0.5% SDS solution was added to the release medium. All samples were then filtered through a 0.22 μm pore size filter. The drug concentration was measured on High Performance Liquid Chromatography (HPLC) and the cumulative drug release was calculated.
The cumulative release amount is calculated as follows:
in this formula, er% represents the cumulative amount of drug released, V e Representing the sample volumes at different points in time. At different time points, C i Representing real-time drug concentration; v O Represents the volume of released medium in each centrifuge tube; m drug Indicating the initial Res mass contained in each dialysis bag.
The in vitro cumulative release profiles of the different formulations in different media are shown in figure 9. From FIG. 9, it can be seen that the release rate of TPGS-lipo @ Res-NC in phosphate buffer solution for 36h (87.21. + -. 1.86)%, is higher than that of the free drug solution (38.77. + -. 2.089%). Similarly, 94.91 + -2.60% of the drug was released from the drug-loaded liposomes in HCl solution, while the release rate of the free drug was 49.31 + -1.75% in 36 h. Meanwhile, the drug release rate of the drug-loaded liposome in double distilled water is 89.21 +/-1.41 percent, and the drug release rate in free drug suspension is only 35.01 +/-2.58 percent. Res-NC and TPGS-lipo @ Res-NC were observed to dissolve faster than the free drug in all three media. It can also be seen that the dissolution rate of TPGS-lipo @ Res-NC in three media is slower than that of Res-NC, but the accumulative release within 36h is not much different from that of Res-NC, which indicates that Res-NC improves the solubility of Res. TPGS-lipo @ Res-NC improves the stability of Res-NC in external environments.
4. Caco-2 cytotoxicity assay for TPGS-lipo @ Res-NC
The cytotoxicity of different concentrations of TPGS-lipo @ Res-NC on Caco-2 was determined by MTT method. The result shows that TPGS-lipo @ Res-NC has less toxicity to Caco-2 cells, and the cell survival rate is still more than 80% when the concentration of TPGS-lipo @ Res-NC is 200ug/mL after 48h of culture, so that the TPGS-lipo @ Res-NCo is proved to have very low cytotoxicity. The results of the experiment are shown in FIG. 10.
5. Caco-2 cell uptake and cell localization experiments of C6@ Lipo and C6@ TPGS-Lipo
Coumarin is used as a fluorescent dye, and the preparation method in the first embodiment is adopted to prepare the C6@ Lipo and the C6@ TPGS-Lipo. The uptake of C6, C6@ Lipo and C6@ TPGS-Lipo by caco-2 cells at different concentrations of the formulation and at different times was observed.
The cell nucleus is specifically stained by a cell nucleus staining method, and the distribution of the C6@ TPGS-Lipo in the cells after the endocytosis of the caco-2 cells is observed by an inverted fluorescence microscope.
The experimental results show that the fluorescence intensity of the cells can be increased along with the increase of the uptake time and concentration of different preparations, which indicates that the preparation has time and concentration dependence on caco-2 cells. As can be seen from FIG. 11, the Caco-2 cells have higher uptake of the C6@ TPGS-Lipo, because in the Caco-2 cell model, TPGS can remarkably promote the uptake of Caco-2 cells, which indicates that the TPGS modified mesoliposome can improve the oral availability of the drug, thereby proving that the TPGS-Lipo @ Res-NC has better bioavailability. The results of the experiment are shown in FIG. 11.
Aiming at the problems that the resveratrol is insoluble in water and low in bioavailability, the invention adopts a micro-medium grinding method to prepare the resveratrol into the nanocrystal, the nanocrystal has small particle size and high drug loading, and the dissolution rate of the resveratrol is improved. And the resveratrol nanocrystal is encapsulated by the TPGS modified liposome, so that the stability of the nanocrystal is improved, and the uptake of resveratrol by caco-2 cells is enhanced. The bioavailability of the resveratrol is improved by combining the advantages of the two preparations.
It will be appreciated by a person skilled in the art that the scope of the invention as referred to in the present application is not limited to the embodiments with a specific combination of the above-mentioned features, but also covers other embodiments with any combination of the above-mentioned features or their equivalents without departing from the inventive concept. For example, the above features may be replaced with (but not limited to) features having similar functions disclosed in the present application.
Claims (7)
1. The preparation method of the resveratrol nanocrystalline liposome based on TPGS modification is characterized by comprising the following steps:
s1: mixing resveratrol and a stabilizer, performing ultrasonic dispersion, adding zirconia beads, grinding under magnetic stirring, and absorbing the nano suspension after grinding to obtain a resveratrol nanocrystal solution;
s2: dissolving soybean lecithin, cholesterol and TPGS with an organic solvent, evaporating the solution under reduced pressure to remove the organic solvent until a milky film is formed, adding the resveratrol nanocrystal solution and the buffer solution for ultrasonic hydration, and then performing ultrasonic treatment by using an ultrasonic probe to obtain the TPGS modified resveratrol nanocrystal liposome;
the stabilizer is sodium dodecyl sulfate, and the mass ratio of the resveratrol to the stabilizer is 2;
the mass ratio of the soybean lecithin, cholesterol and TPGS is (20);
the organic solvent is trichloroethane.
2. The preparation method of the TPGS-modified resveratrol nanocrystal liposome based on the TPGS 1, wherein the buffer solution is a phosphate buffer solution, and the volume ratio of the resveratrol nanocrystal solution to the phosphate buffer solution is 1.
3. The preparation method of the resveratrol nanocrystal liposome based on TPGS modification of claim 1, wherein the zirconia beads have a size of 0.5mm.
4. The preparation method of the TPGS-modified resveratrol nanocrystal liposome based on claim 1, wherein the rotation speed of magnetic stirring is 1500r/min, and the grinding time is 12h.
5. The preparation method of the TPGS-modified resveratrol nanocrystal liposome based on claim 1, wherein the ultrasonic hydration time is 30min.
6. The preparation method of the TPGS-modified resveratrol nanocrystal liposome based on claim 1, wherein the power of the ultrasonic probe is 150W, the ultrasonic time is 10min, and the ultrasonic is 8s, and the interval is 4s.
7. Use of the TPGS-modified-based resveratrol nanocrystal liposome of any one of claims 1-6 in preparation of an oral formulation.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1951369A (en) * | 2006-11-03 | 2007-04-25 | 李万忠 | Coated nanoliposomes of resveratrol and preparation method thereof |
| CN101991538A (en) * | 2009-08-14 | 2011-03-30 | 浙江工业大学 | TPGS-containing liposome composition and application thereof |
| CN103040754A (en) * | 2012-12-20 | 2013-04-17 | 中国农业科学院农产品加工研究所 | Resveratrol nano-liposome and preparation method thereof |
| CN104224708A (en) * | 2014-09-13 | 2014-12-24 | 泰山医学院 | Preparation method for magnetic nanoparticle-containing resveratrol composite nanosuspension |
| CN105287378A (en) * | 2014-08-03 | 2016-02-03 | 孙仁 | Preparation method of doxorubicin liposome |
| CN105853378A (en) * | 2016-05-24 | 2016-08-17 | 齐鲁工业大学 | Resveratrol trinocotinate nanocrystal quick release capsule preparation and preparation technology thereof |
| CN111920771A (en) * | 2020-09-21 | 2020-11-13 | 河南大学 | Resveratrol nano-liposome and preparation method and application thereof |
-
2022
- 2022-10-19 CN CN202211278212.7A patent/CN115350290B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1951369A (en) * | 2006-11-03 | 2007-04-25 | 李万忠 | Coated nanoliposomes of resveratrol and preparation method thereof |
| CN101991538A (en) * | 2009-08-14 | 2011-03-30 | 浙江工业大学 | TPGS-containing liposome composition and application thereof |
| CN103040754A (en) * | 2012-12-20 | 2013-04-17 | 中国农业科学院农产品加工研究所 | Resveratrol nano-liposome and preparation method thereof |
| CN105287378A (en) * | 2014-08-03 | 2016-02-03 | 孙仁 | Preparation method of doxorubicin liposome |
| CN104224708A (en) * | 2014-09-13 | 2014-12-24 | 泰山医学院 | Preparation method for magnetic nanoparticle-containing resveratrol composite nanosuspension |
| CN105853378A (en) * | 2016-05-24 | 2016-08-17 | 齐鲁工业大学 | Resveratrol trinocotinate nanocrystal quick release capsule preparation and preparation technology thereof |
| CN111920771A (en) * | 2020-09-21 | 2020-11-13 | 河南大学 | Resveratrol nano-liposome and preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| HA, EUN-SOL等: "《Solubility of trans-resveratrol in Transcutol HP + water mixtures at different temperatures and its application to fabrication of nanosuspensions》", 《JOURNAL OF MOLECULAR LIQUIDS》 * |
| KUK, DO-HOON等: "《Development of a resveratrol nanosuspension using the antisolvent precipitation method without solvent removal, based on a quality by design (QbD) approach》", 《PHARMACEUTICS》 * |
| 王鸿森等: "《基于 Box-Behnken Design 设计优化白藜芦醇纳米混悬剂的制备工艺》", 《广东药科大学学报》 * |
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