A nanogel for promoting intestinal absorption and its preparation method and application

Abstract

The present invention belongs to the field of biomedicine technology, and specifically relates to a nanogel that promotes intestinal absorption and its preparation method and application. The nanogel that promotes intestinal absorption provided by the present invention is a nanogel that promotes intestinal absorption through Ca 2+ Cross-linked selenized mercapto sodium alginate, as an active factor delivery system, can not only protect the active factors from being degraded by gastric acid, but also achieve intestinal targeting through intestinal mucus anchoring and inhibit the efflux of P-glycoprotein on the cell membrane of intestinal mucosal epithelial cells, thereby achieving intestinal targeted delivery of active factors and promoting cellular absorption of active factors. It is of great significance for improving the bioavailability of active factors and has broad application prospects in the creation of functional foods and the research and development of intestinal targeted drugs.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to a nanogel for promoting intestinal absorption, and a preparation method and application thereof. Background Art

[0002] Enteric-coated soft capsules are formulated by adding special pharmaceutical polymers to the capsule shell or undergoing special treatment. These capsules remain insoluble in the stomach, but only begin to disintegrate in the intestines, releasing the active pharmaceutical ingredients and exerting local or systemic therapeutic effects. The decomposition and release mechanisms of enteric-coated soft capsules in the intestines can be summarized into three aspects: chemical decomposition, enzymatic decomposition, and microbial decomposition. Chemical decomposition of enteric-coated soft capsules means that the capsule shell material does not disintegrate during oral administration into the stomach, but rapidly disintegrates once in the intestines. Currently, acrylic resins are commonly used as pH-sensitive carrier materials. These copolymers can be modified to achieve varying pH sensitivities by varying the R group. They are stable in the low pH environment of the stomach and are not destroyed by digestive enzymes, but begin to dissolve upon entering the intestines (pH > 5).

[0003] Numerous nutrients, including polyphenols, possess excellent antioxidant and anti-inflammatory properties and have important applications in food, medicine, and other fields. However, low bioavailability, resulting from low absorption rates and susceptibility to gastric acid decomposition, significantly limits the effectiveness of these substances or intestinal absorbed drugs. Currently, although numerous systems have achieved intestinal-targeted delivery based on pathways such as gastrointestinal pH shifts, electrostatic interactions with mucus, and degradation by intestinal enzymes or microorganisms, and most of these systems can achieve intestinal-targeted release, their bioavailability enhancement is limited or they contain allergenic substances. For example, CN112999151A provides an oral paclitaxel composite micelle, the preparation of which uses P-glycoprotein (P-gp) inhibitors such as cyclosporine and tacrolimus to enhance paclitaxel bioavailability, but the bioavailability enhancement rate is low. CN108697683A discloses a method for preparing an oral taxane composition, but the preparation process uses surfactants such as polysorbate 80 and polyoxyethylene castor oil, which are prone to allergic reactions in humans.

[0004] A necessary condition for improving the bioavailability of active ingredients (nutrients / drugs) is that they are efficiently taken up, internalized, and absorbed by intestinal epithelial cells. However, two P-gp molecules on the intestinal mucosal epithelial cell membrane form a transport cavity. When the active ingredient diffuses through the phospholipid bilayer into the cell, P-gp directly transports the charged or neutral active ingredient from the cavity and pumps it directly out of the cell through the plasma membrane by the cytosol, which has a direct impact on the absorption efficiency and bioavailability of the active factor penetrating the intestinal mucosal epithelial cell membrane. Therefore, inhibiting the P-gp efflux pump action of intestinal mucosal epithelial cells and promoting the absorption of the active ingredients embedded therein by intestinal epithelial cells is often the most effective way to improve the bioavailability of active ingredients. At present, there are few reports on carriers that can achieve intestinal targeted delivery of active factors and promote their intestinal absorption behavior and have simple preparation methods. Summary of the Invention

[0005] The purpose of the present invention is to provide a carrier that can achieve intestinal targeted delivery of active factors and promote their intestinal absorption behavior, and the preparation method is simple.

[0006] Based on the above objectives, the present invention meets this demand in the art by providing a nanogel that promotes intestinal absorption and a preparation method and application thereof.

[0007] On the one hand, the present invention relates to a nanogel for promoting intestinal absorption, comprising: sodium selenium mercapto alginate is cross-linked in a calcium salt solution to form the nanogel for promoting intestinal absorption.

[0008] Furthermore, in the nanogel for promoting intestinal absorption provided by the present invention, the Ca 2+ Provided by calcium salts. Specifically, calcium salts are harmless or beneficial to organic life and can provide Ca 2+ Chemical salts such as calcium chloride, calcium lactate, calcium carbonate, and calcium phosphate; preferably, the calcium salt is calcium lactate.

[0009] Specifically, the present invention provides a method for preparing nanogel, comprising: adding 0.5 to 3.0 mg mL -1 The selenized mercapto sodium alginate is dissolved in deionized water and stirred until completely dissolved; it is added dropwise to a calcium salt solution with a mass fraction of 0.5% to 3.0%, and then stirred for 1 to 5 hours. The sample is collected and freeze-dried to obtain a nanogel.

[0010] Furthermore, in the nanogel for promoting intestinal absorption provided by the present invention, the ratio of the selenized sodium mercapto alginate to the calcium salt is 0.2-1.0:0.1-0.5 by mass.

[0011] Furthermore, in the nanogel for promoting intestinal absorption provided by the present invention, the preparation method of the selenized sodium mercaptoalginate comprises: esterifying sodium alginate with thioglycolic acid to obtain sodium mercaptoalginate; and mixing sodium selenite with the sodium mercaptoalginate, followed by reduction with an acidic reducing agent to obtain the selenized sodium mercaptoalginate. Specifically, the acidic reducing agent is selected from one of α-ketoglutaric acid, ascorbic acid and its salts, and sulfurous acid and its salts; preferably, the acidic reducing agent is ascorbic acid.

[0012] Illustratively, the present invention provides a method for preparing selenized sodium mercaptoalginate, comprising: adding 0.4-2.0 mL of ascorbic acid solution (100 mM) to every 3.5 mL of sodium mercaptoalginate solution (0.1-0.5%, w / v) under continuous stirring, followed by dropwise addition of 0.1 mL of sodium selenite solution (100-400 mM), and continuous stirring for 12 h; dialyzing in deionized water for 24 h using a dialysis bag (MWCO: 3500 Da) to remove excess ascorbic acid; and freeze-drying to obtain selenized sodium mercaptoalginate.

[0013] Furthermore, in the nanogel for promoting intestinal absorption provided by the present invention, the ratio of the sodium mercaptoalginate to the sodium selenite is 1.0:0.5-4.0 by mass.

[0014] In another aspect, the present invention relates to a nanocapsule comprising: the aforementioned nanogel encapsulating an active ingredient; the active ingredient being a food functional ingredient or an enteric drug. Specifically, the food functional ingredient of the present invention is a nutrient with a low absorption rate and / or easily decomposed by gastric acid; the nutrient comprises a polyphenol, such as resveratrol, curcumin, quercetin, or berberine. Specifically, the enteric drug of the present invention is selected from any one of the taxanes, camptothecins, flavonoids, vincristines, anthraquinones, podophyllotoxins, doxorubicin, retinoids, cyclosporines, dihydropyridines, and berberines, or derivatives thereof.

[0015] Furthermore, in the nanogel for promoting intestinal absorption provided by the present invention, the nanogel is used to inhibit the action of the P-gp efflux pump of intestinal mucosal epithelial cells, thereby promoting the absorption of the active ingredient embedded therein by intestinal epithelial cells.

[0016] For example, the present invention provides a preparation method for encapsulating one of resveratrol, hydroxycamptothecin or doxorubicin hydrochloride in nanogel, comprising: dissolving sodium selenide mercaptoalginate in deionized water, stirring until completely dissolved to obtain 0.5-3.0 mg·mL -1 1 mL of resveratrol ethanol solution (4-12 mg mL -1 ), ethanol solution of hydroxycamptothecin (0.5~3mg·mL-1 ), doxorubicin hydrochloride aqueous solution (0.5-3 mg mL -1 ) and stirred overnight; each 1 mL of the mixture was added dropwise to a 0.5% to 3.0% calcium salt solution with stirring, and then stirred for 1 to 5 hours. The sample was collected and freeze-dried to obtain a nanogel embedded with resveratrol, hydroxycamptothecin or doxorubicin.

[0017] Inflammatory bowel disease is mostly caused by intestinal oxidative stress, and the occurrence and development of intestinal oxidative stress are also particularly complex. A sharp increase in ROS content in the intestine is a recognized sign, and antioxidant strategies are currently one of its effective treatments. Polyphenols have been used to improve intestinal oxidative stress due to their excellent antioxidant, anti-inflammatory effects and biosafety. However, polyphenols or intestinal absorption drugs have inherent defects such as poor targeting, easy excretion by the kidneys, and poor absorption, which greatly limit their effectiveness. According to an embodiment of the present invention, the protective effect of nanogel on resveratrol prevents it from being destroyed by gastric acid and enzymes, thereby improving its delivery stability. Nanogel improves the bioavailability of polyphenols or intestinal absorption drugs by inhibiting the efflux of P-gp on intestinal epithelial cells.

[0018] Therefore, the present invention further claims protection for the use of the nanogel in the preparation of functional foods or intestinal targeted drugs.

[0019] Compared with the prior art, the technical solution provided by the present invention has the following beneficial effects or advantages:

[0020] The nanogel provided by the present invention is a kind of nanogel that promotes intestinal absorption. 2+ Cross-linked selenized mercapto sodium alginate, as an active factor delivery system, can not only protect the active factors from being degraded by gastric acid, but also achieve intestinal targeting through intestinal mucus anchoring and inhibit the efflux of P-glycoprotein on the cell membrane of intestinal mucosal epithelial cells, thereby achieving intestinal targeted delivery of active factors and promoting cellular absorption of active factors. It is of great significance to improve the bioavailability of active factors and has broad application prospects in the creation of functional foods and the research and development of intestinal targeted drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 These are the infrared spectra of sodium selenide mercapto alginate, nanogel, resveratrol, and nanogel@resveratrol.

[0022] Figure 2 This is a diagram showing the scavenging effects of ascorbic acid, resveratrol and nanogel@resveratrol on OH·, DPPH· and ABTS·.

[0023] Figure 3Cumulative release curves of active ingredients of three representative nanogels@active ingredients in simulated gastric fluid (pH 2.2), simulated duodenal fluid (pH 5.0) and simulated small intestinal fluid (pH 7.0). DETAILED DESCRIPTION

[0024] The technical solutions of the present invention are described below with reference to the following embodiments; however, the present invention is not limited to the following embodiments.

[0025] In order to enable those skilled in the art to better understand and implement the technical solution of the present invention, the present invention is further described below with reference to specific embodiments and drawings, but the embodiments are not intended to limit the present invention.

[0026] The experimental methods and detection methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials are commercially available unless otherwise specified.

[0027] Example 1

[0028] This embodiment provides a nanogel and a nanocapsule prepared therefrom. The nanocapsule is a nanogel-encapsulated resveratrol (nanogel@resveratrol).

[0029] This embodiment illustrates the use of nanogels to encapsulate polyphenols. Other polyphenols, such as curcumin, quercetin, and sophodiesterin, have similar properties to resveratrol and can achieve the technical benefits of this invention using the same method. The term "properties" here does not refer to pharmacological properties, but rather to the relationship between the encapsulating shell and the encapsulated contents.

[0030] Thiolated sodium alginate was prepared according to Khalid's method [International Journal of Biological Macromolecules, 2020, 164: 2691]. To 3.5 mL of sodium thioalginate solution (0.3%, w / v) was added 0.4 mL of ascorbic acid (100 mM) with continuous stirring, followed by dropwise addition of 0.1 mL of sodium selenite (100 mM) and continuous stirring for 12 h. The solution was dialyzed in deionized water for 24 h using a dialysis bag (MWCO: 3500 Da) to remove excess ascorbic acid. Freeze-dried to obtain selenized sodium thioalginate.

[0031] Dissolve 3 mg of selenium-thiolated sodium alginate in 3 mL of deionized water and stir until completely dissolved. Add 1 mL of the mixture dropwise to a 1% calcium lactate solution under continuous stirring. Continue stirring for 1 hour after the addition is complete. Centrifuge (3000 rpm, 3 min) and freeze-dry to obtain Ca 2+ Cross-linked selenized mercapto-sodium alginate nanogel (ie, nanogel).

[0032] Dissolve 3 mg of sodium selenide alginate in 3 mL of deionized water and stir until completely dissolved. Add 1 mL of ethanol solution of resveratrol (Res) (6 mg mL -1 ) and stirred overnight. 1 mL of the mixture was added dropwise to a 1% calcium lactate solution under continuous stirring. After the addition was complete, stirring was continued for 1 hour. Centrifugation (3000 rpm, 3 min) and freeze-dried to obtain resveratrol-loaded Ca 2+ Cross-linked selenized mercapto-sodium alginate nanogel (i.e., nanogel@resveratrol).

[0033] like Figure 1 In the infrared spectrum shown, the characteristic peaks of the benzene ring skeleton of resveratrol appear at 1597, 1517 and 1433 cm -1 The characteristic peak of phenolic hydroxyl in its structure appears at 3300~3500cm -1 The characteristic peak of thiol in selenized thiol alginate appears at 2711cm -1 , 532cm -1 -Se-H characteristic signal appears at 2+ After cross-linking, the -CH in selenized mercapto alginate is at 2895 and 2983 cm -1 The symmetric and asymmetric stretching vibration intensities at 1720-1130 cm -1 All peaks appearing in the region shift to lower wavenumber regions, and the weakening of the peak intensity is the result of spatial effects, indicating that the nanogel has been successfully prepared. In the infrared spectrum of the nanogel@resveratrol, all of the above characteristic peaks are present, proving that the nanogel@resveratrol has been successfully prepared.

[0034] The nanogel was dissolved in deionized water and the particle size and distribution of the nanogel@resveratrol were measured using a laser particle size analyzer. h =211.7±3.03nm, PDI: 0.167±0.009, showing a single peak, indicating a uniform particle size distribution. According to the literature [Nano Letter, 2020, 20, 2:1352.], particles within this size range can smoothly pass through the three-dimensional network structure of the intestinal mucus layer, thereby increasing the probability of active factors being taken up by intestinal epithelial cells.

[0035] Dissolve a certain amount of freeze-dried resveratrol nanogel powder in 3 mL of pH 7.4 PBS and stir for 24 hours. Add 3 mL of ethanol to the mixture and ultrasonically centrifuge for 10 minutes. Centrifuge the mixture and measure the absorbance of the supernatant at 306 nm using a UV-visible spectrophotometer to calculate the resveratrol loading (%) and encapsulation efficiency (%) in the nanogel:

[0036] Drug loading % = mass of resveratrol in nanogel@resveratrol / mass of nanogel@resveratrol × 100%

[0037] Encapsulation efficiency % = mass of resveratrol in nanogel@resveratrol / mass of resveratrol initially added × 100%

[0038] It was determined that the nanogel loading was 18.1% and the encapsulation efficiency was 62.19%.

[0039] Example 2

[0040] This embodiment provides a method for preparing a nanogel encapsulating hydroxycamptothecin (nanogel@hydroxycamptothecin).

[0041] This embodiment illustrates the use of nanogels to encapsulate enteric drugs. Other enteric drugs, such as taxanes, camptothecins, flavonoids, vincristines, anthraquinones, podophyllotoxins, doxorubicin, retinoids, cyclosporines, dihydropyridines, and berberine, have similar properties to hydroxycamptothecin and can achieve the technical benefits of this invention using the same method. The term "properties" here does not refer to pharmacological properties but rather to the relationship between the encapsulating shell material and the encapsulated contents.

[0042] Dissolve 6 mg of sodium selenide alginate in 3 mL of deionized water and stir until completely dissolved. Add 1 mL of ethanol solution of hydroxycamptothecin (HCPT) (1 mg mL -1 ) and stirred overnight. 1 mL of the mixture was added dropwise to a 0.5% calcium chloride solution under continuous stirring. After the addition was complete, stirring was continued for 1 hour. Centrifugation (3000 rpm, 3 min) and freeze-dried to obtain the Ca-containing hydroxycamptothecin. 2+ Cross-linked selenized mercapto-sodium alginate nanogel (ie, nanogel@hydroxycamptothecin).

[0043] Example 3

[0044] This embodiment provides a method for preparing a nanogel encapsulating doxorubicin (nanogel@doxorubicin).

[0045] This embodiment illustrates the use of nanogels to encapsulate enteric drugs. Other enteric drugs, such as taxanes, camptothecins, flavonoids, vincristines, anthraquinones, podophyllotoxins, doxorubicin, retinoids, cyclosporines, dihydropyridines, and berberines, have similar properties to doxorubicin and can achieve the technical benefits of the present invention using the same method. The term "properties" here does not refer to pharmacological properties but rather to the relationship between the encapsulating shell material and the encapsulated contents.

[0046] Dissolve 6 mg of sodium selenide alginate in 3 mL of deionized water and stir until completely dissolved. Add 1 mL of doxorubicin hydrochloride (DOX·HCl) aqueous solution (1 mg·mL -1 ) and stirred overnight. 1 mL of the mixture was added dropwise to a 3% calcium phosphate solution under continuous stirring. After the addition was complete, stirring was continued for 1 hour. Centrifugation (3000 rpm, 3 min) and freeze-dried to obtain the Ca-phosphate solution loaded with doxorubicin. 2+ Cross-linked selenized mercapto-sodium alginate nanogel (i.e., nanogel@adriamycin).

[0047] Example 4

[0048] The nanogels loaded with resveratrol, hydroxycamptothecin and doxorubicin (Examples 1 to 3) were dissolved in deionized water, and the particle size and distribution of the nanogels were measured using a laser particle size analyzer. As shown in Table 1, the D h The particle sizes of the nanoparticles were 211.7±13.03nm, 196.1±8.91nm and 204.6±10.16nm respectively, and the polydispersity index (PDI) was less than 0.21, indicating that the particle size distribution was uniform. h When the particle size is smaller than 250nm, it can pass through the three-dimensional network structure of the intestinal mucus layer smoothly, which can increase the chance of active factors being taken up by intestinal epithelial cells.

[0049] Example 5

[0050] This example evaluates the entrapment behavior of active ingredients (resveratrol, hydroxycamptothecin and doxorubicin hydrochloride) in nanogels.

[0051] Dissolve a certain amount of freeze-dried powder of nanogel@resveratrol, nanogel@hydroxycamptothecin, and nanogel@doxorubicin in 3 mL of pH 7.4 PBS, stir for 24 hours, add 3 mL of ethanol, and ultrasonically centrifuge for 10 minutes. Centrifuge the mixture, and measure the absorbance of the supernatant at 306, 391, and 484 nm using a UV-visible spectrophotometer to calculate the resveratrol loading (%) and encapsulation efficiency (%) in the nanogel:

[0052] Drug loading % = (mass of active ingredient in nanogel@active ingredient / mass of nanogel@active ingredient) × 100%

[0053] Encapsulation efficiency % = (mass of active ingredient in nanogel@active ingredient / mass of initial added active ingredient) × 100%

[0054] Table 1: Hydrodynamic diameters (D) of three representative nanogels@active ingredientsh ), polydispersity index (PDI), drug loading capacity (LC) and encapsulation efficiency (EE) parameter table

[0055]

[0056] As shown in Table 1, the loading capacity of the nanogel for resveratrol was 18.18%, and the encapsulation efficiency was 62.19%; the loading capacity of the nanogel for hydroxycamptothecin was 20.22%, and the encapsulation efficiency was 70.42%; the loading capacity of the nanogel for doxorubicin was 31.36%, and the encapsulation efficiency was 84.44%.

[0057] Example 6

[0058] This example provides the performance test results of nanogel@active ingredient.

[0059] (1) Determination of nanogel intestinal mucus adhesion properties

[0060] The adhesion properties of the nanogels at pH 2.2, 5.0, and 7.0 were evaluated by periodic acid Schiff colorimetry. The results are shown in Table 2.

[0061] Table 2: Mucin adhesion of resveratrol, hydroxycamptothecin, doxorubicin hydrochloride, nanogels, and three representative nanogels with active ingredients at pH 2.2, 5.0, and 7.0

[0062]

[0063] As shown in Table 2, under the three physiological environments, the adhesion of nanogel@active ingredient to mucin is the highest. This is determined by its structure and composition. At pH 2.2, due to the weak hydrogen bonds between the large amount of sialic acid and sulfonic acid groups in mucin and mucin, as well as the weak hydrogen bonds and van der Waals interactions on the surface of the nanogel, all samples have similar adhesion to mucin; at pH 5.0, the calcium cross-linked layer of the nanogel has gradually begun to break, a small amount of active ingredients are released, and the nanogel exposes more -CH2 and can also adhere to mucin. The adhesion of nanogel@resveratrol, nanogel@hydroxycamptothecin and nanogel@doxorubicin to mucin at pH 5.0 reached 26.89±0.0020, 33.24±0.0123 and 36.29±0.1162μg, respectively; At 7.0, the adhesion to mucin reached as high as 72.84±0.0458, 94.41±1.2897, and 103.29±2.4408 μg, respectively. This was attributed to the complete destruction of the nanogel structure, which exposed a large amount of -COOH, -OH, and -CH2, and the synergistic adhesion of released resveratrol, hydroxycamptothecin, and doxorubicin to mucin. These results indicate that the adhesion of nanogel@active ingredient to mucin is closely related to the release amount of the active ingredient and the morphology of the nanogel. This also demonstrates that intestinal targeting of active ingredients via nanogels is feasible and that achieving intestinal targeting is a prerequisite for improving the bioavailability of active ingredients.

[0064] (2) Evaluation of the free radical scavenging properties of resveratrol, nanogel and nanogel@resveratrol.

[0065] Resveratrol and nanogel@resveratrol were digested with simulated gastric juice and simulated intestinal juice. Figure 2 As shown in the results, compared with ascorbic acid, the scavenging rates of resveratrol for ·DPPH and ·ABTS were only 15.11% ± 0.55% and 59.88% ± 0.80%. After nanogel encapsulation, the scavenging rates of resveratrol for ·DPPH and ·ABTS were as high as 33.41% ± 2.95% and 80.64% ± 0.14%, respectively. This indicates that the nanogel can prevent the destruction of resveratrol by gastric acid and ROS in the stomach, ensuring its efficient antioxidant activity.

[0066] (3) Targeted release effect of nanogel@active ingredients in simulated gastrointestinal fluid.

[0067] like Figure 3As shown, the nanogels remained virtually unchanged in simulated gastric and duodenal fluids, resulting in a cumulative release of resveratrol of 2.8% ± 0.9% in these fluids. With continued incubation in simulated small intestinal fluid, the nanogel structure completely disintegrated, ultimately leading to a cumulative release of 92.4% ± 3.2%, demonstrating that the system can achieve intestinal-targeted release. Nanogels with hydroxycamptothecin and nanogels with doxorubicin exhibited similar release behaviors in simulated gastrointestinal fluid.

[0068] (4) Evaluation of the inhibitory effect of nanogel on P-gp.

[0069] Resveratrol was stained with rhodamine 123. The cells were suspended in PBS to make 1×10 6 A single-cell suspension of 100 μg / mL was inoculated into 15 mL centrifuge tubes, with 1 mL per tube. The suspension was centrifuged at 1000 rpm for 5 minutes. 0.5 mL of nanogel (200 μmol / mL) was added, the cells were incubated in an incubator for 60 minutes, and then placed in an ice bath to terminate the reaction. The cells were centrifuged at 1000 rpm for 5 minutes at 4°C, washed twice with ice-cold PBS, and then 20 μL of resveratrol (500 μmol / mL) solution was added. This was designated the (nanogel + resveratrol) experimental group. A positive control group was added with 0.5 mL of verapamil solution (50 μmol / mL) plus 20 μL of resveratrol (500 μmol / mL) solution; a blank control group was added with 0.5 mL of PBS. A negative control group was added with 0.5 mL of PBS plus 20 μL of resveratrol (500 μmol / mL) solution. The cells were resuspended in 0.5 mL of PBS, and the intracellular fluorescence intensity was measured using a flow cytometer. The above experiment was performed using hydroxycamptothecin and doxorubicin, and the intracellular fluorescence intensity was measured using flow cytometry. The measurement results are shown in Table 3.

[0070] Table 3: Fluorescence intensity in Caco-2 cells

[0071]

[0072]

[0073] As shown in Table 3, PBS does not inhibit P-gp. Therefore, upon entering Caco-2 cells, only a small amount of the active ingredients is taken up, while the vast majority is pumped out of the cells by P-gp. Consequently, the intracellular fluorescence intensities of resveratrol, hydroxycamptothecin, and doxorubicin are only 65, 42, and 68, respectively. Verapamil, a P-gp inhibitor and substrate, affects its transport function. Therefore, it promotes the smooth uptake and internalization of the active ingredients by Caco-2 cells, with fluorescence intensities of the three active substances reaching 102, 89, and 121, respectively. Co-incubation of the nanogel with cells accelerated the uptake of resveratrol, hydroxycamptothecin, and doxorubicin, with intracellular fluorescence intensities reaching 120, 145, and 168, respectively. This demonstrates that the nanogel has a more pronounced P-gp inhibitory effect than verapamil and can effectively enhance the bioavailability of the active ingredients.

[0074] As described above, the present invention can be better implemented. The above embodiments only describe the preferred implementation methods of the present invention and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various changes and improvements made to the technical solutions of the present invention by ordinary technicians in this field should fall within the protection scope determined by the present invention.

Claims

1. A nanogel for promoting intestinal absorption, characterized in that: include: Sodium selenide mercaptoalginate in Ca 2+ Cross-linking occurs in the solution to form the nanogel that promotes intestinal absorption; The preparation method of the selenized sodium mercaptoalginate comprises: subjecting sodium alginate to an esterification reaction with thioglycolic acid to obtain sodium mercaptoalginate; mixing sodium selenite with the sodium mercaptoalginate and then reducing the mixture with an acidic reducing agent to obtain the selenized sodium mercaptoalginate; Calculated by mass ratio, the ratio of the sodium mercapto alginate to the sodium selenite is 1.0:0.5-4.

0.

2. The nanogel according to claim 1, wherein The Ca 2+ The solution is a calcium salt solution, and the calcium salt is selected from any one of calcium chloride, calcium lactate, calcium carbonate, and calcium phosphate.

3. The nanogel according to claim 2, characterized in that The mass fraction of calcium salt in the calcium salt solution is 0.5-3%.

4. A nanocapsule, characterized in that: include: The nanogel according to any one of claims 1 to 3 is used to embed the active ingredient; The active ingredient is a food functional ingredient or an intestinal absorption drug.

5. The nanocapsule according to claim 4, characterized in that The food functional ingredient is polyphenol; The polyphenol is selected from one of resveratrol, curcumin, quercetin and sophora flavescens.

6. The nanocapsule according to claim 4, characterized in that The nanogel is used to inhibit the P-gp efflux pump action of intestinal mucosal epithelial cells and promote the absorption of the active ingredients embedded therein by intestinal epithelial cells.

7. Use of the nanogel according to any one of claims 1 to 3 in the preparation of functional foods.

8. Use of the nanogel according to any one of claims 1 to 3 in the preparation of intestinal targeted drugs.

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