A method for efficiently preparing lignin nanoparticles with a hollow structure and applications thereof

Abstract

The application discloses a method for efficiently preparing lignin nanoparticles with a hollow structure and application thereof, and belongs to the technical field of material grading and purification. The method comprises the following steps: lignin is prepared into a nanoparticle suspension through a reverse solvent precipitation method, and the prepared lignin nanoparticle suspension is graded by controlling a centrifugal speed, so that the lignin nanoparticles with the hollow structure are obtained. The method has the advantages of simple operation, short time consumption, high efficiency, green environmental protection, low cost and easy industrial production. Meanwhile, vancomycin can be loaded by adding the vancomycin in a self-assembly process, so that a new idea is provided for high-value utilization of lignin.

Description

Technical Field

[0001] This invention belongs to the field of material classification and purification technology, and more specifically, relates to a method and application for efficiently preparing lignin nanoparticles with hollow structures. Background Technology

[0002] Lignin is a complex natural aromatic polymer composed of phenylpropane structural units. It is the second most abundant biomass resource in nature after cellulose, characterized by its rich availability, low cost, biodegradability, and good reinforcing properties. Furthermore, its surface contains numerous functional groups, such as hydroxyl, methoxy, carbonyl, and carboxyl groups, giving it excellent multifunctionality and potential applications in many fields. It has already been used in high-value applications such as adhesives, surfactants, UV shielding, and drug delivery. However, currently, lignin is mainly used as a low-value fuel, with less than 2% of it used in high-value applications. Its complex structure, large molecular weight, poor processability, inherent heterogeneity, and poor dispersibility in water severely limit its multi-field applications.

[0003] Hollowed-out lignin nanoparticles possess advantages such as lower mass than solid particles, higher surface area, and structural tunability, leading to extensive research in antibacterial, filler, and drug delivery applications. The benzene ring structure and phenolic units of lignin endow it with excellent antibacterial capabilities. Compared to pristine lignin, lignin nanoparticles (LNPs) have a larger specific surface area and more functional groups distributed on their surface, resulting in superior antibacterial properties. Yang et al.'s research found that small-sized lignin nanoparticles can penetrate bacterial cells and lower the intracellular pH, ultimately depleting adenosine triphosphate (ATP) to kill the bacteria, confirming the excellent antibacterial properties of lignin nanoparticles. With breakthroughs in lignin chemistry, lignin structure, and preparation techniques, lignin-based drug delivery systems have attracted attention in drug transport due to their natural and non-toxic characteristics. Zhou et al. proposed a simple method for preparing targeted hollow lignin nanoparticles (LHNPs) and achieved the loading and targeted delivery of doxorubicin hydrochloride (DOX). The lignin nanoparticles prepared by this method can respond to external magnetic fields and folic acid receptors, and their good targeting ability increases cellular uptake.

[0004] Generally, lignin of different molecular weights contains different types and contents of active functional groups. Therefore, if lignin can be classified according to molecular weight and functional group enrichment to obtain lignin fractions with low polydispersity or high reactivity, it will significantly promote the development and utilization of downstream lignin products. Commonly used lignin classification methods include membrane classification, acid precipitation classification, organic solvent classification, ionic liquid classification, and hydrothermal classification. Membrane classification is an important direction in current lignin classification research, with advantages such as high efficiency, simplicity, and no secondary pollution. However, its large-scale application is greatly limited due to problems such as expensive equipment, short lifespan, and high maintenance and costs. Acid precipitation classification is simple to operate, has a short reaction time, and low energy consumption, but the purity of the obtained lignin is lower compared to other classification methods, and the acid recovery cost is high, which may cause potential pollution. Summary of the Invention

[0005] To address the aforementioned problems in existing technologies, the technical problem this invention aims to solve is to provide a method for efficiently preparing lignin nanoparticles with a hollow structure. This method is simple to operate, time-efficient, and highly effective. Another technical problem this invention aims to solve is to provide the application of the aforementioned lignin nanoparticles with a hollow structure in drug loading.

[0006] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0007] A method for efficiently preparing lignin nanoparticles with hollow structures is disclosed. The method involves preparing a lignin nanoparticle suspension using a tetrahydrofuran-water system as an antisolvent precipitation method, and then fractionating the suspension by controlling the rotation speed to obtain uniform lignin nanoparticles with hollow structures. The hollow structures of the uniform lignin nanoparticles have a diameter of 423–715 nm and a surface area ratio of 19.98–34.3%.

[0008] Preferably, the lignin is amphiphilic lignin. The amphiphilic lignin is crude lignin or purified lignin. The preparation process of purified lignin is as follows: crude lignin is dissolved in dichloroethane / ethanol solution, and after complete dissolution, diethyl ether solution is added, and the mixture is stirred thoroughly to precipitate lignin; the precipitate is centrifuged at 8000 rpm for 5 min, and the precipitate is washed 3 times with diethyl ether and 1 time with petroleum ether, respectively. After washing, the precipitate is dried for 12 h to obtain purified lignin.

[0009] Preferably, the controlled rotation speed grading is used to grade lignin nanoparticles with and without hollow structures at a rotation speed of 5000 rpm.

[0010] Preferably, no prior grading is required; the lignin nanoparticle suspension can be prepared directly using the antisolvent precipitation method of the tetrahydrofuran-water system, where tetrahydrofuran is the solvent and the aqueous solution is the antisolvent.

[0011] The method for efficiently preparing lignin nanoparticles with a hollow structure includes the following steps:

[0012] 1) Dissolve lignin in tetrahydrofuran first, then add it dropwise to an aqueous solution and stir to obtain a lignin nanoparticle suspension;

[0013] 2) The prepared lignin nanoparticle suspension was centrifuged at 1000 rpm, and the precipitate was dried in a vacuum drying oven to obtain 1000 rpm lignin nanoparticles.

[0014] 3) Take the supernatant after centrifugation at 1000 rpm and continue centrifuging at 3000 rpm. Take the precipitate and dry it in a vacuum drying oven to obtain lignin nanoparticles at 3000 rpm.

[0015] 4) Take the supernatant after centrifugation at 3000 rpm and continue centrifuging at 5000 rpm. Take the precipitate and dry it in a vacuum drying oven to obtain lignin nanoparticles at 5000 rpm.

[0016] 5) Take the supernatant after centrifugation at 5000 rpm and continue centrifuging at 8000 rpm. Take the precipitate and dry it in a vacuum drying oven to obtain lignin nanoparticles at 8000 rpm.

[0017] 6) Take the supernatant after centrifugation at 8000 rpm and continue centrifuging at 10000 rpm. Take the precipitate and dry it in a vacuum drying oven to obtain lignin nanoparticles at 10000 rpm.

[0018] The centrifugation time was 5 minutes, and the drying temperature in the vacuum drying oven was 40°C. o C, drying time is 48h.

[0019] The method for efficiently preparing lignin nanoparticles with hollow structures is described above, and lignin nanoparticles with hollow structures are prepared.

[0020] The application of the lignin nanoparticles with hollow structure in drug loading.

[0021] In the aforementioned application, lignin and the drug are simultaneously added to tetrahydrofuran, and then an aqueous solution is added dropwise to obtain a mixed suspension. The mixed suspension is then centrifuged to obtain drug-loaded lignin nanoparticles.

[0022] The application described herein refers to the use of vancomycin.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0024] 1) This invention uses centrifugation to classify lignin nanoparticles. By directly classifying the product (lignin nanoparticles), uniform lignin nanoparticles with hollow structures are prepared. Compared with traditional classification methods, this method is simple to operate, time-saving, efficient, environmentally friendly, low-cost, and easy to industrialize.

[0025] 2) This invention uses only a self-assembly method to load the drug vancomycin onto lignin nanoparticles, and the content can be detected by HPLC. It has a good release effect with a release rate of over 80%.

[0026] 3) This invention realizes a method for the simultaneous preparation of lignin nanoparticles and drug loading, enabling efficient drug loading and providing a new approach for the efficient utilization of drugs and the high-value utilization of lignin in the biomedical field. Attached Figure Description

[0027] Figure 1 TEM image of the coarse lignin nanoparticles prepared in Example 1;

[0028] Figure 2 TEM images of coarse lignin nanoparticles after centrifugation and fractionation at different speeds in Example 2;

[0029] Figure 3 The figures show TEM images of lignin nanoparticles after centrifugation at 1000 and 3000 rpm in Example 2. In the figures, 1000 rpm represents the particle size distribution of lignin nanoparticles separated at 1000 rpm; 1000 rpm-HS represents the diameter distribution of the hollow structure of lignin nanoparticles separated at 1000 rpm; 3000 rpm represents the particle size distribution of lignin nanoparticles separated at 3000 rpm; and 3000 rpm-HS represents the diameter distribution of the hollow structure of lignin nanoparticles separated at 3000 rpm.

[0030] Figure 4 The images show TEM structure analysis of lignin nanoparticles after centrifugation at 5000, 8000, and 10000 rpm in Example 2. In the images, 5000 rpm represents the particle size distribution of lignin nanoparticles separated at 5000 rpm; 5000 rpm-HS represents the diameter distribution of the hollow structure of lignin nanoparticles separated at 5000 rpm; 8000 rpm represents the particle size distribution of lignin nanoparticles separated at 8000 rpm; and 10000 rpm represents the particle size distribution of lignin nanoparticles separated at 10000 rpm.

[0031] Figure 5TEM images of purified lignin nanoparticles after centrifugation and fractionation at 3000, 5000, and 8000 rpm in Example 3;

[0032] Figure 6 The images show the TEM results of lignin nanoparticles purified after centrifugation at 3000, 5000, and 8000 rpm in Example 3. In the images, KLNPs-3000 shows the particle size distribution of lignin nanoparticles prepared by lignin separation and purification at 3000 rpm; KLNPs-3000-HS shows the diameter distribution of the hollow structure of lignin nanoparticles prepared by lignin separation and purification at 3000 rpm; KLNPs-5000 shows the particle size distribution of lignin nanoparticles prepared by lignin separation and purification at 5000 rpm; KLNPs-5000-HS shows the diameter distribution of the hollow structure of lignin nanoparticles prepared by lignin separation and purification at 5000 rpm; KLNPs-8000 shows the particle size distribution of lignin nanoparticles prepared by lignin separation and purification at 8000 rpm; and KLNPs-8000-HS shows the diameter distribution of the hollow structure of lignin nanoparticles prepared by lignin separation and purification at 8000 rpm.

[0033] Figure 7 The image shows a typical lignin nanoparticle; in the image, a is a side view of the hollow structure and b is a top view of the hollow structure.

[0034] Figure 8 TEM images of lignin nanoparticle solutions with different vancomycin loadings prepared in Example 4;

[0035] Figure 9The figures show TEM results of lignin nanoparticle solutions prepared in Example 4 with different vancomycin loadings. In the figures, KLNPs represents the particle size distribution of vancomycin-loaded lignin nanoparticles prepared with 0 mg vancomycin; KLNPs-HS represents the diameter distribution of the hollow structure of vancomycin-loaded lignin nanoparticles prepared with 0 mg vancomycin; VCM-KLNPs-10 represents the particle size distribution of vancomycin-loaded lignin nanoparticles prepared with 10 mg vancomycin; VCM-KLNPs-10-HS represents the diameter distribution of the hollow structure of vancomycin-loaded lignin nanoparticles prepared with 10 mg vancomycin; VCM-KLNPs-50 represents the particle size distribution of vancomycin-loaded lignin nanoparticles prepared with 50 mg vancomycin; and VCM-KLNPs-50-HS represents the particle size distribution of lignin nanoparticles prepared with 50 mg vancomycin. Diameter distribution of the hollow structure of vancomycin-loaded lignin nanoparticles prepared with 100 mg vancomycin; particle size distribution of vancomycin-loaded lignin nanoparticles prepared with 100 mg vancomycin; diameter distribution of the hollow structure of vancomycin-loaded lignin nanoparticles prepared with 100 mg vancomycin; particle size distribution of vancomycin-loaded lignin nanoparticles prepared with 200 mg vancomycin; diameter distribution of the hollow structure of vancomycin-loaded lignin nanoparticles prepared with 200 mg vancomycin; diameter distribution of the hollow structure of vancomycin-loaded lignin nanoparticles prepared with 200 mg vancomycin; diameter distribution of the hollow structure of vancomycin-loaded lignin nanoparticles prepared with 200 mg vancomycin; diameter distribution of the hollow structure of vancomycin-loaded lignin nanoparticles prepared with 200 mg vancomycin.

[0036] Figure 10 The elemental analysis diagram of vancomycin-loaded lignin nanoparticles (VCM-KLNPs) in the TEM-mapping spectrum;

[0037] Figure 11 The figure shows the drug loading analysis of vancomycin-loaded lignin nanoparticles. In the figure, (a) is the high performance liquid chromatogram of vancomycin C18, (b) is the standard curve of vancomycin, (c) is the release concentration curve, and (d) is the release rate curve. Detailed Implementation

[0038] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described below with reference to specific embodiments. Unless otherwise specified, the technical means used in the following embodiments are all conventional means well known to those skilled in the art.

[0039] The centrifuge used in this invention is a KH20R centrifuge manufactured by Hunan Keda Scientific Instruments Co., Ltd., with a centrifugal radius of 63 mm and a g value of 9.8 m / s. 2 The centrifuge and its corresponding rotation speed are shown in Table 1 below:

[0040] Table 1 Correspondence between Rotation Speed ​​and Centrifugal Force

[0041]

[0042] The crude lignin used in this invention is sulfate lignin (Kraft lignin), which is derived from bamboo processing residues, and the extraction and purification method used is the Bjorkman process.

[0043] The tetrahydrofuran, diethyl ether, dichloroethane, ethanol, and petroleum ether used in the following examples were all purchased from Nanjing Chemical Reagent Co., Ltd., and were all chemically pure. Vancomycin was purchased from Aladdin, CAS number 1404-90-6.

[0044] The vancomycin detection method in the following examples is as follows: high performance liquid chromatography is used, with 0.05 M ammonium dihydrogen phosphate (pH=4.0) and acetonitrile solution as the mobile phase, elution is performed through a C18 column at a flow rate of 0.8 mL / min, and the vancomycin concentration is determined under a 220 nm ultraviolet light detector.

[0045] Example 1

[0046] Dissolve 20 mg of crude lignin in 10 mL of tetrahydrofuran, then add 40 mL of distilled water dropwise at a rate of 4 mL / min to the tetrahydrofuran solution. Stir the mixture at 600 rpm, centrifuge at 10,000 rpm for 5 min, and collect the precipitate at 40 mL / min. o The lignin nanoparticles were dried in a vacuum drying oven at C for 48 h, and a 0.1% concentration (g / v) aqueous dispersion of lignin nanoparticles was prepared for later use.

[0047] After sonicating the prepared lignin nanoparticle aqueous dispersion for 10 min, it was dropped onto the surface of a TEM-specific copper mesh. The surface moisture was evaporated under a heat lamp, and the microstructure of the lignin nanoparticles was observed using a transmission electron microscope (TEM). Figure 1 .

[0048] Figure 1 TEM images of the microstructure of lignin nanoparticles show that lignin exists as spherical particles of varying sizes, with large particles exhibiting distinct porous structures on their surfaces. This indicates that lignin can be prepared into lignin nanoparticles using a tetrahydrofuran / water system. However, the results also reveal that the preparation process is influenced by numerous factors, resulting in extremely uneven nanoscale size and potentially unstable properties. Therefore, finding a method to prepare uniform lignin nanoparticles is essential.

[0049] Example 2

[0050] A method for efficiently preparing lignin nanoparticles with a hollow structure includes the following steps:

[0051] 1) Dissolve 20 mg of crude lignin in 10 mL of tetrahydrofuran, then add 40 mL of distilled water dropwise at a rate of 4 mL / min to the tetrahydrofuran solution, and stir the solution at a rate of 600 rpm to prepare a lignin nanoparticle suspension.

[0052] 2) The prepared lignin nanoparticle suspension was centrifuged at 1000 rpm for 5 min, and the precipitate was placed in a vacuum drying oven at 40°C. o C. Dry for 48 hours to obtain lignin nanoparticles at 1000 rpm;

[0053] 3) Take the supernatant after centrifugation at 1000 rpm and centrifuge again at 3000 rpm for 5 min. Collect the precipitate and place it in a vacuum drying oven at 40°C. o C. Drying for 48 hours yields lignin nanoparticles at 3000 rpm;

[0054] 4) Centrifuge the supernatant from 3000 rpm for another 5 min at 5000 rpm, and collect the precipitate in a vacuum drying oven at 40°C. o C. Drying for 48 hours yields lignin nanoparticles at 5000 rpm;

[0055] 5) Centrifuge the supernatant from 5000 rpm for another 5 min at 8000 rpm, and collect the precipitate in a vacuum drying oven at 40°C. o C. Drying for 48 hours yields lignin nanoparticles at 8000 rpm;

[0056] 6) Take the supernatant after centrifugation at 8000 rpm and centrifuge again at 10000 rpm for 5 min. Collect the precipitate and place it in a vacuum drying oven at 40°C. o C. Drying for 48 hours yields lignin nanoparticles at 10,000 rpm.

[0057] The dried lignin nanoparticles were prepared into a 0.1% concentration (0.1 g lignin / 100 ml water) aqueous dispersion and dropped onto a copper mesh surface for TEM testing. The TEM results were analyzed using ImageJ software, as shown in Table 2. Figure 2-4 .

[0058] Table 2. Microstructure results of coarse lignin nanoparticles after fractionation at different rotation speeds.

[0059]

[0060] From Table 2 and Figure 2-4It is known that lignin nanoparticles separated at a low rotation speed of 1000 rpm contain more impurities, while at speeds above 8000 rpm, the hollow structures within many lignin nanoparticles disappear. Based on the particle size and hollow diameter results in Table 2, it can be observed that the overall particle size of the lignin nanoparticles decreases with increasing separation speed, demonstrating good ability to be classified according to particle size. Through adjustment, a larger surface area facilitates greater contact between active groups and the external environment, aiding in further modification or expression of active group effects, while a smaller volume fraction helps to load more drugs or active factors during self-assembly. Therefore, it has flexible applicability in the biomedical field.

[0061] Example 3

[0062] 10 g of crude lignin was dissolved in 100 mL of dichloroethane / ethanol (2:1, v / v) solution to remove surface impurities. After complete dissolution, 1000 mL of diethyl ether solution was added, and the mixture was stirred thoroughly to precipitate lignin. The precipitate was centrifuged at 8000 rpm for 5 min, and washed three times with 25 mL of diethyl ether at 8000 rpm for 5 min. Finally, the precipitate was washed once with 25 mL of petroleum ether at 8000 rpm for 5 min to fully evaporate the surface organic solvent, and then vacuum dried for 12 h to obtain purified lignin.

[0063] Purified lignin was prepared into a nanoparticle suspension using the antisolvent precipitation method described in Example 2, and the suspension was fractionated by centrifugation at 3000, 5000, and 8000 rpm. Furthermore, the dried lignin nanoparticles were prepared into a 0.1% aqueous dispersion and dropped onto a copper mesh surface for TEM testing. The TEM results were analyzed using ImageJ software, as shown in Table 3. Figure 5-6 .

[0064] Table 3. Microstructure and surface potential of purified lignin nanoparticles after fractionation at different rotation speeds.

[0065]

[0066] From Table 3 and Figure 5-6It was found that the particle size of lignin nanoparticles decreased with increasing rotational speed, decreasing from 1179±69 nm to 836±204 nm (Table 3). The size of the hollow structure in the lignin nanoparticles prepared in Example 3 also decreased with decreasing particle size, exhibiting a larger contact area with the external environment and lower spherical mass, suggesting potential applications as drug carriers and gel enhancers. The purified lignin nanoparticles showed stable size and good dispersibility, with 5000 rpm being the optimal separation speed. Furthermore, at 8000 rpm, the hollow structure of some lignin nanoparticles disappeared, indicating that this method has the ability to perform preliminary classification of lignin nanoparticles containing and without hollow structures.

[0067] The crude lignin and the purified lignin prepared in Example 3 were centrifuged at speeds of 3000, 5000, and 8000 rpm to obtain lignin nanoparticles, which were then analyzed by 600M NMR. 31 The functional group content of P was detected, as shown in Table 4.

[0068] Table 4. Functional group content of lignin nanoparticles at different rotation speeds.

[0069]

[0070] Figure 7 The figures show typical lignin nanoparticles. In the figures, a is a side view of the hollow structure, and b is a top view of the hollow structure. It can be seen that lignin has a distinct hollow structure, with a thicker lignin wall at the end away from the hollow structure, which indirectly confirms that lignin nanoparticles are formed through layer-by-layer self-assembly and stacking. As shown in Table 4, lignin has a higher content of hydrophilic groups—total phenolic hydroxyl and carboxyl groups—at high rotation speed. Therefore, it is speculated that this may be due to the slower formation of lignin nanoparticles caused by the larger number of hydrophilic groups. As the content of the antisolvent (water) increases, the concentration difference between the inside and outside gradually decreases, resulting in insufficient lignin wall formation, collapse, and a reduction in particle size, or even the disappearance of the hollow structure. This suggests the ability to adjust the size of the hollow structure of nanoparticles by controlling the hydrophilic-hydrophobic ratio in the reaction system.

[0071] Example 4

[0072] 100 mg of purified lignin prepared in Example 3 was dissolved in 50 mL of tetrahydrofuran with 0 mg, 10 mg, 50 mg, 100 mg, and 200 mg of vancomycin, respectively. Drug-loaded lignin nanoparticles (VCM-KLNPs-10, VCM-KLNPs-50, VCM-KLNPs-100, and VCM-KLNPs-200) were prepared by dropwise addition of 200 mL of aqueous solution at a rate of 4 mL / min. After centrifugation at 5000 rpm for 5 min, the precipitate was dried in a vacuum drying oven for 48 h and a 0.1% concentration of drug-loaded lignin nanoparticle aqueous dispersion was prepared. After sonication for 10 min, the dispersion was dropwise added to the surface of a TEM-specific copper mesh, and the surface moisture was evaporated under a heat lamp. The microstructure of the lignin nanoparticles was observed using transmission electron microscopy (TEM), as shown in Table 5. Figure 8-9 .

[0073] Table 5. Microstructure and surface potential analysis of lignin nanoparticle solutions with different vancomycin loadings.

[0074]

[0075] From Table 5 and Figure 8-9 It can be seen that the loading of vancomycin has little effect on the size of lignin nanoparticles, which is around 1000 nm. However, the size of its hollow structure increases with the increase of the content of the hydrophobic drug vancomycin. The result is consistent with the speculation obtained in Example 3: more hydrophilic groups lead to slower lignin nanoparticle formation. As the content of antisolvent (water) increases, the concentration difference between the inside and outside gradually decreases, the lignin wall is not formed enough, and the collapse leads to a decrease in particle size or even the disappearance of the hollow structure. It has the ability to adjust the size of the hollow structure of nanoparticles by controlling the hydrophilic-hydrophobic ratio in the reaction system.

[0076] A vancomycin concentration detection method was constructed using C18-HPLC, and its surface elemental distribution was analyzed by mapping mode. The prepared VCM-KLNPs-10, VCM-KLNPs-50, VCM-KLNPs-100, and VCM-KLNPs-200 were used for vancomycin sustained-release assays, and the results are shown below. Figure 10 and Figure 11 .

[0077] The specific steps for vancomycin concentration detection are as follows:

[0078] 1) Weigh 12 mg of vancomycin-loaded lignin nanoparticles, add 6 mL of 0.01 M PBS solution to prepare a 2 mg / mL suspension, and sonicate for 10-30 min;

[0079] 2) Take 5 mL of the suspension prepared in step 1) into a dialysis bag, place it in 100 mL of PBS solution, and dialyze at 100 rpm. Samples were taken at time points of 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 h. During each sampling, 3 mL of liquid was taken, and 3 mL of PBS solution was added. Each sample was centrifuged at 10000 rpm for 5 min, filtered through a 0.22 μm filter membrane, and prepared as an HPLC sample. The determined concentration was used to plot the vancomycin sustained-release curve.

[0080] 3) Take another 1 mL of the suspension prepared in step 1), centrifuge at 10000 rpm for 5 min, filter through a 0.22 μm filter membrane, and prepare an HPLC sample. The measured content is used to calculate the drug loading rate of vancomycin.

[0081]

[0082] Among them, M VCM The mass of vancomycin in the suspension prepared in step 1) is g; M VCM-LNPs The mass of vancomycin-loaded lignin nanoparticles in the suspension prepared in step 1) is g.

[0083] Table 6. Surface elemental distribution and drug loading rate of lignin nanoparticles with different vancomycin loadings.

[0084]

[0085] From Table 6 and Figure 10 The successful determination of the Cl element distribution indicates that vancomycin was successfully loaded onto lignin nanoparticles, and the lignin nanoparticles with a vancomycin loading of 100 mg showed the highest detection rate for vancomycin, demonstrating good loading capacity.

[0086] Depend on Figure 11 It can be seen that the chromatographic system constructed in this invention has good detection performance. Meanwhile, vancomycin-loaded lignin nanoparticles exhibit good sustained-release effects, with sustained-release rates all greater than 80%. They show the optimal loading effect at a loading of 100 mg, with a drug loading rate of 6.45%, indicating that the lignin nanoparticles prepared by this method have good drug delivery capabilities.

[0087] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for efficiently preparing lignin nanoparticles with a hollow structure, characterized in that, A lignin nanoparticle suspension was prepared by antisolvent precipitation using a tetrahydrofuran-water system. Uniform lignin nanoparticles with a hollow structure were obtained by controlling the rotation speed for fractionation. The hollow structure diameter of the uniform lignin nanoparticles with the hollow structure was 247–549 nm, and the hollow structure surface area accounted for 10.8–21.2%. The controlled rotation speed fractionation involved separating lignin nanoparticles with and without hollow structures at a rotation speed of 5000 rpm.

2. The method for efficiently preparing lignin nanoparticles with a hollow structure according to claim 1, characterized in that, The lignin is an amphiphilic lignin.

3. The method for efficiently preparing lignin nanoparticles with a hollow structure according to claim 1, characterized in that, No prior fractionation is required; lignin nanoparticle suspensions can be prepared directly using the tetrahydrofuran-water system as an antisolvent precipitation method, where tetrahydrofuran is the solvent and the aqueous solution is the antisolvent.

4. The method for efficiently preparing lignin nanoparticles with a hollow structure according to claim 1, characterized in that, Includes the following steps: 1) Dissolve lignin in tetrahydrofuran first, then add it dropwise to an aqueous solution and stir to obtain a lignin nanoparticle suspension; 2) The prepared lignin nanoparticle suspension was centrifuged at 1000 rpm, and the precipitate was dried in a vacuum drying oven to obtain 1000 rpm lignin nanoparticles. 3) Take the supernatant after centrifugation at 1000 rpm and continue centrifuging at 3000 rpm. Take the precipitate and dry it in a vacuum drying oven to obtain lignin nanoparticles at 3000 rpm. 4) Take the supernatant after centrifugation at 3000 rpm and continue centrifuging at 5000 rpm. Take the precipitate and dry it in a vacuum drying oven to obtain lignin nanoparticles at 5000 rpm.

5. The method for efficiently preparing lignin nanoparticles with a hollow structure according to claim 4, characterized in that, The centrifugation time was 5 minutes, and the drying temperature in the vacuum drying oven was 40°C.

6. The method for efficiently preparing lignin nanoparticles with hollow structures according to any one of claims 1-5 is used to prepare lignin nanoparticles with hollow structures.

7. The application of the lignin nanoparticles with a hollow structure as described in claim 6 in drug loading.

8. The application according to claim 7, characterized in that, Lignin and the drug were added to tetrahydrofuran simultaneously, and then an aqueous solution was added dropwise to obtain a mixed suspension. The mixed suspension was then centrifuged to obtain drug-loaded lignin nanoparticles.

9. The application according to claim 8, characterized in that, The drug in question is vancomycin.

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