CN111363096A - Nano-cellulose hydrogel drug-loading system loaded with garlicin, and preparation and application thereof - Google Patents
Nano-cellulose hydrogel drug-loading system loaded with garlicin, and preparation and application thereof Download PDFInfo
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Abstract
The invention discloses a nano-cellulose hydrogel drug-loading system loaded with garlicin and a preparation method and an application thereof.A garlic straw is taken as a raw material, dried to constant weight, crushed and sieved, extracted by NaOH solution to obtain garlic straw cellulose, and decolored by sodium chlorite; hydrolyzing the garlic straw cellulose by using sulfuric acid to obtain garlic straw nano cellulose; the method comprises the steps of preparing garlic straw nano-cellulose hydrogel and loading garlicin by using garlic straw nano-cellulose, deionized water, ammonium persulfate, acrylamide and N, N-methylene bisacrylamide as raw materials. The hydrogel has the characteristics of good swelling property, moisture retention, good mechanical strength, large drug-loading rate and the like, and has the anti-liver cancer activity of slow release and low cytotoxicity. The invention effectively improves the biocompatibility and stability of the garlicin by loading the garlicin through the garlic straw nano-cellulose hydrogel, thereby having great application prospect in the field of medicine.
Description
Technical Field
The invention belongs to the field of biomedicine, and particularly relates to a nano-cellulose hydrogel loaded with allicin and having anticancer activity, and a preparation method and application thereof.
Background
Allicin is an allyl sulfide-containing compound, which is a main active compound of garlic, and mainly comprises: diallyl monosulfide (DAMS), diallyl disulfide (DADS), and diallyl trisulfide (DATS). Allicin has antibacterial, anticancer and anti-inflammatory effects, so that researches on allicin preparations attract more and more attention and become a hotspot of researches. However, allicin has a strong garlic smell, is extremely unstable in physicochemical property, is easily oxidized under light, heat and alkaline conditions, has a short biological half-life, is rapidly metabolized in vivo, has strong irritation to human mucosa, and greatly limits the application of allicin in the field of medicines and foods.
The polymer hydrogel is a three-position polymer network, has good hydrophilicity, has the characteristics of swelling and insolubility, can load water or solvent which is dozens of times of the weight of the polymer hydrogel, and is widely applied to the field of drug release. The polymer drug-loaded hydrogel mainly achieves the purpose of drug release by corresponding conditions such as pH, temperature, light and the like and destroying corresponding chemical bonds, and more intelligent hydrogels sensitive to factors such as pH, temperature and the like are researched in medicine at present. Cellulose is a hydrophilic high-molecular polysaccharide composed of D-glucosyl, and is a renewable resource with rich sources in the nature. The nano-cellulose is a cellulose modified high molecular compound and has the characteristics of good biocompatibility, biodegradability, high strength, high crystallinity, high transparency, large specific surface area, strong hydrophilicity and the like. The surface of the nano-cellulose is provided with a large amount of hydroxyl groups, and a network structure is further formed among the hydroxyl groups through the action of hydrogen bonds, so that the nano-cellulose colloid can stably exist, and therefore, the nano-cellulose is widely applied to the fields of medical materials and the like.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a nano-cellulose hydrogel drug-loading system loaded with garlicin and a preparation method and application thereof, and solves the problems of instability and low bioavailability of garlicin in the prior art.
The technical scheme of the invention is as follows:
a preparation method of a nano-cellulose hydrogel drug-loading system loaded with garlicin comprises the following steps:
(1): preparing garlic straw cellulose by using garlic straws as a raw material;
(2): processing the garlic straw cellulose obtained in the step (1) into garlic straw nano-cellulose;
(3): preparing garlic straw nano-cellulose hydrogel by taking garlic straw nano-cellulose, acrylic acid, acrylamide and N, N-methylene bisacrylamide as raw materials and performing performance characterization;
(4): the garlicin or the analogues thereof are loaded in the nano-cellulose hydrogel of the garlic straws.
The allicin or the analogue thereof in the step (4) is one or more of the following substances: diallyl trisulfide (DATS), diallyl disulfide (DADS), diallyl monosulfide (DAMS), diallyl tetrasulfide (DATTS), alline, methallyl disulfide, methallyl trisulfide, and allyl sulfide.
The preparation of the garlic straw cellulose in the step (1) comprises the following steps: crushing a sample, sieving the crushed sample with a 100-mesh sieve, removing water-soluble impurities in the sample by using deionized water in advance, removing lignin by using a 5-10% sodium chlorite solution, soaking the sample in a 5-10% NaOH solution for 10-12 hours, removing hemicellulose and impurities, collecting residues, washing the residues to be neutral by using deionized water, dehydrating the residues by using ethanol, drying the residues to constant weight, crushing the residues, and repeatedly sieving the residues with the 100-mesh sieve to obtain the garlic cellulose.
The preparation of the garlic straw nano-cellulose in the step (2) comprises the following steps: the key point of the sulfuric acid method for preparing the garlic straw nano-cellulose is that concentrated H is added in a concentration gradient manner2SO4Fully soaking the garlic straw cellulose in deionized water in advance, placing the garlic straw cellulose on a magnetic stirrer for fully stirring, and then dropwise adding concentrated H2SO4Until the volume concentration is 30 percent, stirring evenly, and adding concentrated H dropwise after 10 minutes2SO4And (3) treating the mixture for 30-60 minutes until the volume concentration is 50-70%, adding absolute ethyl alcohol to obtain white flocculent precipitate, eluting the white flocculent precipitate to be neutral, and freeze-drying the white flocculent precipitate.
And (3) preparing the allicin straw nano-cellulose hydrogel, wherein bubbles in the hydrogel are removed by a high-speed centrifugation method when the hydrogel is not completely solidified.
The step (4) loads the garlicin or the analogues thereof in the garlic straw nano-cellulose hydrogel, and the specific method comprises the following steps: preparing allicin or allicin analogue with ethanol, wherein the concentration of the allicin or allicin analogue is 1mg/mL, placing 200mg of nano-cellulose hydrogel in deionized water, swelling to constant weight, then placing the nano-cellulose hydrogel in an allicin ethanol solution, placing the allicin ethanol solution in a constant-temperature oscillator, oscillating for 24 hours at 25 ℃, centrifuging for 5 minutes at 4000rpm, removing supernatant, and drying the precipitated drug-loaded hydrogel at 37 ℃ to obtain the allicin-loaded nano-cellulose hydrogel.
The nano-cellulose hydrogel drug-loading system loaded with garlicin and prepared by the method.
An application of a nano-cellulose hydrogel drug-loaded system loaded with garlicin in the field of anti-liver cancer.
The invention has the beneficial effects that:
(1) the garlic straw nano-cellulose prepared by the method has small particle size and uniform shape, and the hydrogel prepared by taking the garlic straw nano-cellulose as a raw material has good swelling property, water absorption, moisture retention and mechanical property;
(2) according to the invention, the garlicin is used as a model drug, loaded on the garlic straw nano-cellulose hydrogel and subjected to drug encapsulation/release experiments, and test results show that the hydrogel prepared by the invention can well improve the biocompatibility of the garlicin, and has high drug encapsulation rate and good slow release effect. The stability of the allicin is obviously improved.
(3) The hydrogel prepared by the invention has the functions of low toxicity and response to pH value, and can control the release speed of the drug by adjusting the pH value to achieve the purpose of treatment.
Drawings
Fig. 1 is an infrared analysis of the garlic straw cellulose, nanocellulose and nanocellulose hydrogel prepared in example 1: (a) garlic straw cellulose; (b) a nanocellulose; (c) a nanocellulose hydrogel;
fig. 2 is an X-ray diffraction pattern of the garlic straw cellulose, nanocellulose and nanocellulose hydrogel prepared in example 1: (a) garlic straw cellulose; (b) a nanocellulose; (c) a nanocellulose hydrogel;
FIG. 3 is a scanning electron microscope image of the garlic straw cellulose, nanocellulose and nanocellulose hydrogel prepared in example 1, (a-1) garlic straw cellulose (1000 ×), (b-1) nanocellulose (1000 ×), (c-1)1000 × nanocellulose hydrogel, (c-2)10000 × nanocellulose hydrogel);
fig. 4 is a polarizing microscope image of the garlic straw cellulose and nanocellulose prepared in example 1: (a) garlic straw cellulose; (b) a nanocellulose; (c) nanocellulose hydrogel surfaces (transmitted light); (d) the morphology of the nanocellulose particles;
FIG. 5 is a particle size analysis of the garlic straw nanocellulose prepared in example 1;
FIG. 6 is the release profiles of allicin and allicin-loaded nanocellulose hydrogel of example 1 in simulated gastric fluid, simulated intestinal fluid and buffer at pH 5.5; (A) allicin release profile; (B) a nanocellulose hydrogel release profile of allicin;
FIG. 7 is a graph showing the proliferation effect of the blank hydrogel and the allicin-loaded nanocellulose hydrogel prepared in example 1 on HepG2 cell (A) and L02 cell (B).
Detailed Description
The present invention is further illustrated by the following examples and the accompanying drawings, which are given by way of illustration only and are not to be construed as limiting the present invention.
Example 1
Taking 100g of garlic straws, crushing and sieving by a 100-mesh sieve, soaking in 2L of deionized water, removing water-soluble components, repeatedly washing garlic straw residues with deionized water until the garlic straw residues are clear, and drying the residues; preparing 7.5% sodium chlorite solution (adjusting pH value to 3.8-4.0 with HCl solution), water bathing at 75 deg.C for 2 hr for removing lignin from straw and bleaching, eluting to neutrality, and dehydrating with anhydrous ethanol; soaking the dried residue in 10% NaOH, treating at room temperature for 12 hr to remove hemicellulose and impurities, collecting the residue, washing with deionized water to neutrality, dehydrating with ethanol, drying to constant weight, pulverizing, and sieving with 100 mesh sieve to obtain garlic straw cellulose 17.9 g.
Further weighing 10g of garlic straw cellulose, adding 30% of H2SO4Then adding concentrated H drop by drop2SO4Stirring for 45min until the final concentration is 60% and the final volume is 200mL, adding anhydrous ethanol to obtain white flocculent precipitate, eluting to neutral, and lyophilizing to obtain 8.13 g.
Further weighing 4g of garlic straw nano-cellulose, dissolving in 100mL of deionized water to prepare a 4% garlic straw nano-cellulose solution, and stirring at room temperature for 2 hours to completely disperse the garlic straw nano-cellulose solution; then 0.1g of ammonium persulfate is added, the mixture is stirred for 15 minutes at the temperature of 60 ℃, then 20mL of acrylic acid with the neutralization degree of 70%, 4g of acrylamide and 0.12g of N, N-methylene bisacrylamide are sequentially added, and the mixture is stirred evenly for 10 minutes at the temperature of 70 ℃, so that the garlic straw nano-cellulose hydrogel is obtained.
Swelling the freeze-dried hydrogel with deionized water, measuring the mass once every 1 hour until the mass of the hydrogel is constant, measuring 10mg of allicin, dissolving the allicin with 50% ethanol to obtain 1mg/mL, placing 50mg of nano-cellulose hydrogel into an allicin solution, placing the nano-cellulose hydrogel into a constant-temperature oscillator, oscillating the nano-cellulose hydrogel at 25 ℃ for 24 hours, and swelling the nano-cellulose hydrogel to the constant weight. And then taking the nano-cellulose hydrogel out of the allicin solution, washing the nano-cellulose hydrogel for 3 times by using a 50% ethanol solution, and further freeze-drying the allicin-nano-cellulose hydrogel to obtain the allicin-loaded nano-cellulose hydrogel. The drug loading and encapsulation efficiency were calculated according to the following formulas:
the absorbance value is measured at its maximum absorption wavelength, based on the maximum amount of drug released. According to the standard curve, the concentration of the nano-cellulose hydrogel is calculated, the drug loading rate of the nano-cellulose hydrogel of the garlic straw is 166.4mg/g, and the encapsulation rate is 83.2%.
Example 2
Taking 100g of garlic straws, crushing and sieving by a 100-mesh sieve, soaking in 2L of deionized water, removing water-soluble components, repeatedly washing garlic straw residues with deionized water until the garlic straw residues are clear, and drying the residues; preparing 5% sodium chlorite solution (adjusting pH value to 3.8-4.0 with HCl solution), water bathing at 70 deg.C for 2 hr for removing lignin from straw and bleaching, eluting to neutrality, and dehydrating with anhydrous ethanol; soaking the dried residue in a certain amount of 5% NaOH, treating at room temperature for 10 hours to remove hemicellulose and impurities, collecting the residue, washing with deionized water to neutrality, dehydrating with ethanol, drying to constant weight, pulverizing, and sieving with 100 mesh sieve to obtain 14.2g of garlic straw cellulose.
Further weighing 10g of garlic straw cellulose, adding 30% of H2SO4Then adding concentrated H drop by drop2SO4And (3) treating the mixture for 60min until the final concentration is 50% and the final volume is 200mL, adding absolute ethyl alcohol to obtain white flocculent precipitate, eluting the precipitate to be neutral, and freeze-drying the precipitate to obtain 7.25 g.
Weighing 5g of garlic straw nano-cellulose, dissolving the garlic straw nano-cellulose in 100mL of deionized water to prepare a 5% garlic straw nano-cellulose solution, and stirring the solution at room temperature for 2 hours to completely disperse the solution; then 0.05g of ammonium persulfate is added, the mixture is stirred for 15 minutes at the temperature of 60 ℃, 25mL of acrylic acid with the neutralization degree of 70%, 3g of acrylamide and 0.1g of N, N-methylene bisacrylamide are sequentially added, and the mixture is stirred evenly for 30 minutes at the temperature of 60 ℃, so that the garlic straw nano-cellulose hydrogel is obtained.
Swelling the freeze-dried hydrogel with deionized water, measuring the mass of the hydrogel once every 1 hour until the mass of the hydrogel is constant, measuring 5mg of allicin, dissolving the allicin in ethanol to obtain 1mg/mL, placing 200mg of nano-cellulose hydrogel in the deionized water, swelling the nano-cellulose hydrogel to constant weight, placing the nano-cellulose hydrogel in an allicin ethanol solution, placing the nano-cellulose hydrogel in a constant temperature oscillator, oscillating the nano-cellulose hydrogel at 25 ℃ for 24 hours, centrifuging the nano-cellulose hydrogel at 4000rpm for 5 minutes, removing supernatant, and drying the precipitated drug-loaded hydrogel at 37 ℃ to obtain the nano-cellulose hydrogel loaded with the allicin. The drug loading and encapsulation efficiency were calculated according to the following formulas:
the absorbance value is measured at its maximum absorption wavelength, based on the maximum amount of drug released. According to the standard curve, the concentration of the nano-cellulose hydrogel is calculated, the drug loading rate of the nano-cellulose hydrogel of the garlic straw is 128.0mg/g, and the encapsulation rate is 64.0%.
Example 3
Taking 100g of garlic straws, crushing and sieving by a 100-mesh sieve, soaking in 3L of deionized water, removing water-soluble components, repeatedly washing garlic straw residues with deionized water until the garlic straw residues are clear, and drying the residues; preparing 10% sodium chlorite solution (adjusting pH value to 3.8-4.0 with HCl solution), water bathing at 80 deg.C for 2 hr for removing lignin from straw and bleaching, eluting to neutrality, and dehydrating with anhydrous ethanol; soaking the dried residue in a certain amount of 10% NaOH, treating at room temperature for 12 hours to remove hemicellulose and impurities, collecting the residue, washing with deionized water to neutrality, dehydrating with ethanol, drying to constant weight, pulverizing, and sieving with 100 mesh sieve to obtain 16.8g of garlic straw cellulose.
Further weighing 10g of garlic straw cellulose, adding 30% of H2SO4Then adding concentrated H drop by drop2SO4Treating for 30min until the final concentration is 70% and the final volume is 200mL, and adding anhydrous ethanol to obtain the final productWhite flocculent precipitate, eluting to neutrality, and lyophilizing to obtain 7.59 g.
Further weighing 4g of garlic straw nano-cellulose, dissolving in 100mL of deionized water to prepare a 4% garlic straw nano-cellulose solution, and stirring at room temperature for 2 hours to completely disperse the garlic straw nano-cellulose solution; then 0.4g of ammonium persulfate is added, the mixture is stirred for 15 minutes at the temperature of 60 ℃, 20mL of acrylic acid with the neutralization degree of 70 percent, 3g of acrylamide and 0.15g of N, N-methylene bisacrylamide are sequentially added, and the mixture is stirred evenly for 10 minutes at the temperature of 70 ℃, thus obtaining the garlic straw nano-cellulose hydrogel
Swelling the freeze-dried hydrogel with deionized water, measuring the mass of the hydrogel once every 1 hour until the mass of the hydrogel is constant, measuring 5mg of allicin, dissolving the allicin in ethanol to obtain 1mg/mL, placing 200mg of nano-cellulose hydrogel in the deionized water, swelling the nano-cellulose hydrogel to constant weight, placing the nano-cellulose hydrogel in an allicin ethanol solution, placing the nano-cellulose hydrogel in a constant temperature oscillator, oscillating the nano-cellulose hydrogel at 25 ℃ for 24 hours, centrifuging the nano-cellulose hydrogel at 4000rpm for 5 minutes, removing supernatant, and drying the precipitated drug-loaded hydrogel at 37 ℃ to obtain the nano-cellulose hydrogel loaded with the allicin. The drug loading and encapsulation efficiency were calculated according to the following formulas:
the absorbance value is measured at its maximum absorption wavelength, based on the maximum amount of drug released. According to the standard curve, the concentration of the nano-cellulose hydrogel is calculated, the drug loading rate of the nano-cellulose hydrogel of the garlic straw is 150.4mg/g, and the encapsulation rate is 75.2%.
Example 4
Taking 100g of garlic straws, crushing and sieving by a 100-mesh sieve, soaking in 3L of deionized water, removing water-soluble components, repeatedly washing garlic straw residues with deionized water until the garlic straw residues are clear, and drying the residues; preparing 10% sodium chlorite solution (adjusting pH value to 3.8-4.0 with HCl solution), water bathing at 70 deg.C for 2 hr for removing lignin from straw and bleaching, eluting to neutrality, and dehydrating with anhydrous ethanol; soaking the dried residue in a certain amount of 5% NaOH, treating at room temperature for 12 hr to remove hemicellulose and impurities, collecting the residue, washing with deionized water to neutrality, dehydrating with ethanol, drying to constant weight, pulverizing, and sieving with 100 mesh sieve to obtain garlic straw cellulose 14.9 g.
Further weighing 10g of garlic straw cellulose, adding 30% of H2SO4Then adding concentrated H drop by drop2SO4And (3) treating the mixture for 45min until the final concentration is 60% and the final volume is 200mL, adding absolute ethyl alcohol to obtain white flocculent precipitate, eluting the white flocculent precipitate to be neutral, and freeze-drying the white flocculent precipitate to obtain 7.14 g.
Further weighing 3g of garlic straw nano-cellulose, dissolving in 100mL of deionized water to prepare a 3% garlic straw nano-cellulose solution, and stirring at room temperature for 2 hours to completely disperse the garlic straw nano-cellulose solution; then 0.3g of ammonium persulfate is added, the mixture is stirred for 15 minutes at the temperature of 60 ℃, then 15mL of acrylic acid with the neutralization degree of 70%, 3g of acrylamide and 0.1g of N, N-methylene bisacrylamide are sequentially added, and the mixture is stirred evenly for 10 minutes at the temperature of 70 ℃, so that the garlic straw nano-cellulose hydrogel is obtained.
Swelling the freeze-dried hydrogel with deionized water, measuring the mass of the hydrogel once every 1 hour until the mass of the hydrogel is constant, measuring 5mg of allicin, dissolving the allicin in ethanol to obtain 1mg/mL, placing 200mg of nano-cellulose hydrogel in the deionized water, swelling the nano-cellulose hydrogel to constant weight, placing the nano-cellulose hydrogel in an allicin ethanol solution, placing the nano-cellulose hydrogel in a constant temperature oscillator, oscillating the nano-cellulose hydrogel at 25 ℃ for 24 hours, centrifuging the nano-cellulose hydrogel at 4000rpm for 5 minutes, removing supernatant, and drying the precipitated drug-loaded hydrogel at 37 ℃ to obtain the nano-cellulose hydrogel loaded with the allicin. The drug loading and encapsulation efficiency were calculated according to the following formulas:
the absorbance value is measured at its maximum absorption wavelength, based on the maximum amount of drug released. According to the standard curve, the concentration of the nano-cellulose hydrogel is calculated, the drug loading rate of the nano-cellulose hydrogel of the garlic straw is 138.4mg/g, and the encapsulation rate is 69.2%.
The intermediate products in the preparation process and the final products of the invention are subjected to performance analysis, and the experimental data are similar to those of the example 1.
The garlic straw nanocellulose and the hydrogel thereof prepared in example 1 are subjected to performance characterization, and a drug release experiment and a cytotoxicity experiment are carried out for determination.
The method comprises the following specific steps:
(1) fourier Infrared Spectroscopy
And (3) characterizing the garlic straw cellulose, the garlic straw nano-cellulose and the garlic straw nano-cellulose hydrogel by adopting infrared spectroscopy (FTIR). And (3) crushing the sample into powder by using a high-speed crusher, and then testing the sample by adopting a KBr tabletting method.
(2) Topography analysis
Observing the microscopic appearances of the garlic straw cellulose and the garlic straw nano cellulose hydrogel by adopting a Scanning Electron Microscope (SEM); and observing the microscopic appearances of the garlic straw cellulose, the garlic straw nano-cellulose and the garlic straw nano-cellulose hydrogel by adopting a metallographic microscope.
(3) Particle size analysis
The particle size of the nanocellulose was determined with a malvern particle size analyzer.
(4) Swelling Performance test
Freeze drying the lyophilized hydrogel, and cutting into 1cm pieces3And (3) weighing. Then soaking the cut freeze-dried hydrogel into deionized water at 25 ℃ for 24h, taking out every 30min, removing water on the surface by using filter paper, and accurately weighing WsUntil the hydrogel is constant in weight. The Equilibrium Swelling Ratio (ESR) of the hydrogel was calculated according to the formula:
in the formula: wsWet weight of hydrogel, g; wdIs a dry gelWeight, g.
(5) Testing of Water absorption and moisture Retention Properties
I, water absorption test: freeze drying the lyophilized hydrogel, and cutting into 1cm pieces3And (3) weighing. Then, the cut freeze-dried hydrogel is immersed in deionized water at 25 ℃ for 24 hours until the hydrogel is constant in weight, and after the water on the surface is removed by filter paper, M is accurately weighedw. The water absorption (WR) of the hydrogel was calculated according to the formula:
in the formula: mwWet weight of hydrogel, g; mdDry weight of hydrogel, g.
II, moisture retention rate test: putting the hydrogel after water absorption and swelling into a centrifuge tube, centrifuging for 5min at 4000r/min by using a centrifuge, and accurately weighing MhCalculate water retention (MR):
in the formula: mdDry hydrogel weight, g; mwMass of hydrogel after water absorption, g; mhMass after hydrogel centrifugation, g.
(6) Mechanical Property test
Cutting the nano cellulose hydrogel of garlic straw into 1.5cm3The hardness, elasticity, cohesiveness, chewiness, tackiness and recovery of the cube-like sample of (1) were measured by a texture analyzer.
(7) Drug Release test
5 mg/part of drug-loaded hydrogel which is freeze-dried to constant weight is further weighed, and the total weight is 3 parts. 500mL of each of simulated gastric fluid, simulated intestinal fluid and buffer solution with pH5.5 are prepared according to Chinese pharmacopoeia (2015 edition) for later use. Preparing 1mg/mL of allicin-hydrogel solution, transferring the solution into a 3500Da dialysis bag, continuously stirring the solution for 60 hours at the temperature of 37 ℃ by using a magnetic stirrer, and calculating the release rate of the allicin-nano hydrogel in three media.
(8) Cytotoxicity experiments:
further, preparing the allicin-nanocellulose hydrogel and the blank hydrogel by using a DMEM blank medium, wherein the concentration of the allicin-nanocellulose hydrogel and the blank hydrogel is 0.01-1 mg/mL, and determining the cytotoxicity of the allicin-nanocellulose hydrogel and the blank hydrogel on human liver HepG2 cells and normal human liver L02 cells.
And (3) testing results:
the garlic straw nano-cellulose hydrogel has better stretchability; the dried hydrogel swells significantly upon absorption of water and increases in volume significantly.
FIG. 1(a) is an infrared spectrogram of garlic straw cellulose, wherein 3000-3750 cm is shown in the chart-1The broad peak of the position is an expansion vibration absorption peak of-OH, 2901cm-1The absorption peak is the stretching vibration peak of C-H in methyl, methylene and methine, 1427cm-1And 1369cm-1The absorption peak shows the bending vibration of the C-H bond, 1161cm-1The absorption peak is an asymmetric stretching vibration peak of cyclic C-O-C in cellulose, and is 1064cm-1The absorption peak is the stretching vibration peak of the C-O group, and is 900cm-1The characteristic that the sample contains β -D glucoside bond is characterized, in the garlic nano cellulose hydrogel, 900cm-1The disappearance of the characteristic peaks indicates the disappearance of β -D glucosidic bonds, which are the bonds between glucose units in cellulose, and the disappearance of the original bonds between substances, which is 3638cm-1And 1050cm-1Absorption peaks at 1651cm were-OH stretching vibration and C-O stretching vibration-1And 1550cm-1The absorption peaks appeared in the positions respectively belong to an amide I band (C ═ O stretching vibration in CONH) and an amide II band (N-H bending vibration in CONH), which indicates that the grafting of the nanocellulose with acrylamide and N, N-methylene bisacrylamide under the garlic straw is successful.
As can be seen from fig. 2, the garlic straw cellulose sample has three diffraction peaks at 2 θ of 16.49 °, 22.50 ° and 34.48 °, which correspond to the crystal planes 101, 002 and 040, respectively, and belong to the cellulose type i; in addition, the garlic cellulose has a strong diffraction peak at 24.67 degrees 2 theta, which is a characteristic peak of hemicellulose, and may be due to the fact that the cellulose contains more hemicellulose. The garlic straw nano-cellulose has diffraction peaks at 2 theta of 12.01 degrees, 19.90 degrees, 20.30 degrees and 21.89 degrees, and belongs to cellulose II type; diffraction peaks also exist at 2 theta (16.49 degrees), 22.5 degrees and 34.48 degrees, but compared with the garlic straw cellulose, the peak height is obviously reduced, which indicates that the cellulose crystal form is changed in the process of preparing the nano cellulose, and the cellulose I type and the cellulose II type coexist in the garlic straw nano cellulose; in addition, a characteristic peak appears at 25.65 degrees 2 theta, which indicates that a six-membered carbon ring structure exists in the sample, and the changes indicate that the crystal structure of the cellulose is destroyed and the crystal form is changed remarkably during the process of processing the cellulose into the nano-cellulose. In the allicin-nanocellulose hydrogel, diffraction peaks at 12.50 °, 19.90 ° and 20.50 ° belong to cellulose type ii, weak diffraction peaks at 14.78 ° and 16.49 ° belong to cellulose type i, and a strong diffraction peak at 32.5 ° and a disappearance of the diffraction peak at 22.50 ° in 2 θ, which indicates that the grafting of acrylamide and N, N-methylene acrylamide to the garlic straw nanocellulose leads to the destruction of the cellulose crystal structure and the transition from cellulose type i to cellulose type ii.
As can be seen from FIG. 3(a-1), the surface of the cellulose of the garlic straw is smooth, which indicates that the purity of the cellulose of the garlic straw extracted by the method is better; the garlic nanocellulose shown in fig. 3(b-1) is in a fine filamentous shape, macroscopic fibrous shape and fragment state of the garlic straw cellulose are maintained, the garlic straw nanocellulose obtained by a scanning electron microscope is slightly longer, and the garlic straw nanocellulose is agglomerated due to a freeze drying process, and the garlic straw cellulose is mutually nucleated into ultrafine nano fibrils; as can be observed from FIGS. 3(c-1) and (c-2), the cross section of the nano-cellulose hydrogel of the garlic straw has a loose porous structure, similar to a honeycomb network structure.
As can be seen from FIG. 4(a), the cellulose of garlic straw has smooth surface and obvious vein structure; the garlic nanocellulose shown in fig. 4(b) is in a shape of a fine rod, and the obtained garlic straw nanocellulose is slightly longer, which is caused by the agglomeration phenomenon of the garlic straw nanocellulose in the freeze drying process; as can be observed from the graphs in fig. 4(c) and (d), the section of the nano-cellulose hydrogel of the garlic straw presents a fine concave-convex structure, and filamentous and flaky grains exist on the surface, so that the nano-cellulose hydrogel of the garlic straw is transparent as a whole and has good uniformity.
As shown in FIG. 5, the particle size of the nano-cellulose of the garlic straw is about 128.3nm, and the PDI value obtained by the test is 0.358, so that the uniformity is better.
As can be seen from FIG. 6(A), allicin is released most frequently at pH5.5, and secondly in simulated intestinal fluid, at a lower rate in simulated gastric fluid; after about 3h, a significant degradation of the allicin occurred, indicating that the allicin had decomposed. As shown in fig. 6(B), the allicin-nanocellulose hydrogel was released after 30h, the release rate was the highest in the simulated intestinal juice, and after 120h, the allicin-nanocellulose hydrogel was released at 83.8% and stabilized in the simulated intestinal juice, the cumulative release rate in the simulated gastric juice was 38.21%, the cumulative release rate in the simulated tumor environment (ph5.5) was 55.38%, and still showed an upward trend. The garlicin is loaded on the garlic straw nano-cellulose hydrogel, which shows that the garlic straw nano-cellulose hydrogel can make the garlicin obtain obvious slow release effect and has better stability.
As can be seen from FIG. 7(A), the allicin and allicin-nanocellulose hydrogel can significantly inhibit the growth of HepG2 cells, wherein the maximal inhibition rate of allicin is 91.54%, IC5055.23. mu.g/mL; while the maximal inhibition rates of the allicin-nano cellulose hydrogel at 24, 48 and 72 hours are respectively 42.37%, 82.31% and 91.78%, and IC50133.56, 70.58 and 52.30. mu.g/mL, respectively. According to the experimental results, the allicin-nanocellulose hydrogel has an obvious inhibition effect on HepG2 cells. Compared with free allicin, the allicin-nano cellulose hydrogel has obvious slow release effect and better stability. Treatment of HepG2 cells with allicin-nanocellulose hydrogel for 72h, IC50Is obviously lower than that of the allicin group, which shows that the nano cellulose hydrogel of the garlic straws improves the bioavailability of the allicin and obviously enhances the inhibition effect on the proliferation of HepG2 cells. As can be seen from FIG. 7(B), the allicin, allicin-nanocellulose hydrogel and blank hydrogel did not significantly damage L02 cells at a concentration range of 10-1000. mu.g/mL.
Table 1 shows the water absorption and moisture retention data of the nanocellulose hydrogel prepared in example 1
As can be seen from the table, the water absorption rate and the water retention rate of the garlic straw nano-cellulose hydrogel are 3048.99% and 99.26%, respectively. The hydrogel has compact crosslinking, loose and porous structure and strong water absorption and retention effects.
Table 2 shows the mechanical property data of the nanocellulose hydrogel prepared in example 1
TABLE 2 mechanical Properties of Garlic straw nanocellulose hydrogels
Although the present invention has been described above with reference to the drawings, the present invention is not limited to the above-described specific embodiments. The invention is not limited to the specific embodiments described herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (8)
1. A preparation method of a nano-cellulose hydrogel drug-loading system loaded with garlicin is characterized by comprising the following steps:
(1): preparing garlic straw cellulose by using garlic straws as a raw material;
(2): processing the garlic straw cellulose obtained in the step (1) into garlic straw nano-cellulose;
(3): preparing garlic straw nano-cellulose hydrogel by taking garlic straw nano-cellulose, acrylic acid, acrylamide and N, N-methylene bisacrylamide as raw materials and performing performance characterization;
(4): the garlicin or the analogues thereof are loaded in the nano-cellulose hydrogel of the garlic straws.
2. The method for preparing the garlicin-loaded nanocellulose hydrogel drug-loaded system of claim 1, wherein the garlicin or its analogue of step (4) is one or more of: diallyl trisulfide, diallyl disulfide, diallyl monosulfide, diallyl tetrasulfide, alline, methallyl disulfide, methallyl trisulfide and allyl sulfide.
3. The preparation method of the nano-cellulose hydrogel drug-loading system loaded with garlicin according to claim 1, wherein the step (1) of preparing the garlic straw cellulose comprises the following steps: crushing a sample, sieving the crushed sample with a 100-mesh sieve, removing water-soluble impurities in the sample by using deionized water in advance, removing lignin by using a 5-10% sodium chlorite solution, soaking the sample in a 5-10% NaOH solution for 10-12 hours, removing hemicellulose and impurities, collecting residues, washing the residues to be neutral by using deionized water, dehydrating the residues by using ethanol, drying the residues to constant weight, crushing the residues, and repeatedly sieving the residues with the 100-mesh sieve to obtain the garlic cellulose.
4. The preparation method of the garlicin-loaded nanocellulose hydrogel drug-loaded system of claim 1, wherein the preparation of the garlic straw nanocellulose in the step (2) comprises the following steps: the key point of the method for preparing the garlic straw nano-cellulose by using the sulfuric acid method is that concentrated sulfuric acid is added in a concentration gradient mode, the garlic straw nano-cellulose is fully soaked in deionized water in advance, the garlic straw nano-cellulose is placed on a magnetic stirrer to be fully stirred, and then concentrated H is dropwise added2SO4Until the volume concentration is 30 percent, stirring evenly, and adding concentrated H dropwise after 10 minutes2SO4And (3) treating the mixture for 30-60 minutes until the volume concentration is 50-70%, adding absolute ethyl alcohol to obtain white flocculent precipitate, eluting the white flocculent precipitate to be neutral, and freeze-drying the white flocculent precipitate.
5. The method for preparing the garlicin-loaded nanocellulose hydrogel drug-loaded system of claim 1, wherein in the step (3), the garlicin straw nanocellulose hydrogel is prepared, and when the hydrogel is not completely solidified, air bubbles in the gel are removed by a high-speed centrifugation method.
6. The preparation method of the nano-cellulose hydrogel drug-loading system loaded with garlicin according to claim 1, wherein the step (4) loads garlicin or the analogues thereof into the nano-cellulose hydrogel loaded with garlic stalks, and the specific method is as follows: preparing allicin or allicin analogue with ethanol, wherein the concentration of the allicin or allicin analogue is 1mg/mL, placing 200mg of nano-cellulose hydrogel in deionized water, swelling to constant weight, then placing the nano-cellulose hydrogel in an allicin ethanol solution, placing the allicin ethanol solution in a constant-temperature oscillator, oscillating for 24 hours at 25 ℃, centrifuging for 5 minutes at 4000rpm, removing supernatant, and drying the precipitated drug-loaded hydrogel at 37 ℃ to obtain the allicin-loaded nano-cellulose hydrogel.
7. The allicin-loaded nanocellulose hydrogel drug delivery system prepared by the method of any one of claims 1-6.
8. An application of a nano-cellulose hydrogel drug-loaded system loaded with garlicin in the field of anti-liver cancer.
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