A sustained-release drug-loaded particle and a preparation method thereof

Abstract

The present application relates to the technical field of drug carrier, in particular to a sustained-release drug-loaded particle and a preparation method thereof.The carrier of the sustained-release drug-loaded particle is based on nanocellulose, and is sequentially subjected to chlorination, amination and cross-linking modification, and is cooperatively compounded with sodium alginate, and the sea buckthorn seed oil is encapsulated by using emulsification-freeze drying technology to form a composite network structure, so that the particle is endowed with excellent sustained-release performance and long-term stability.The unique long-chain alkyl amine introduced in the carrier not only enhances the affinity for hydrophobic drugs, but also realizes a three-stage drug release mode of initial slow release-middle control-late stability by regulating the network structure, effectively prolongs the drug efficacy period, and improves the clinical application value.The sustained-release particle prepared by the present application has high encapsulation efficiency, controllable release, good biocompatibility and storage stability, provides a new idea and method for the development of high-efficiency natural plant oil sustained-release preparation, and has a wide application prospect.

Description

Technical Field

[0001] This invention relates to the field of drug carrier technology, and in particular to a sustained-release drug-loaded particle and its preparation method. Background Technology

[0002] Sea buckthorn seed oil is a natural plant oil rich in various bioactive components, possessing multiple physiological activities such as antioxidation, anti-inflammation, and moisturizing, and has broad application prospects in the fields of medicine, cosmetics, and food supplements. However, the main active components in sea buckthorn seed oil, such as quercetin and other polyphenolic compounds, are easily degraded by external factors such as light, heat, and oxygen, and have strong hydrophobicity, resulting in rapid metabolism and low bioavailability in vivo, which seriously limits its clinical application.

[0003] Traditional sea buckthorn seed oil formulations primarily employ conventional emulsification and microencapsulation technologies for packaging and protection. However, these technologies often suffer from poor stability and insufficient release control. In practical applications, excessively rapid drug release leads to a rapid peak plasma concentration of the active ingredient followed by a rapid decline, reducing therapeutic efficacy and potentially causing local irritation and systemic toxicity. Conversely, excessively slow release may result in insufficient concentrations of the active ingredient, failing to achieve the desired therapeutic effect. Therefore, developing a sea buckthorn seed oil drug delivery system with ideal sustained-release properties is a current research focus and challenge.

[0004] In recent years, bio-based drug delivery materials have attracted widespread attention due to their excellent biocompatibility and biodegradability. Among them, natural polysaccharides such as cellulose derivatives and alginate have shown unique advantages in drug delivery systems. Microcrystalline cellulose, as a commonly used pharmaceutical excipient, has good biocompatibility and chemical stability, but its micron-sized dimensions and limited surface activity restrict its application in fine drug delivery. Sodium alginate, on the other hand, has become an ideal material for constructing controlled-release carriers due to its unique gel-forming ability and pH sensitivity, but when used alone, it often suffers from drawbacks such as insufficient mechanical strength and low affinity for hydrophobic drugs.

[0005] Therefore, developing a biocompatible drug delivery system that can effectively encapsulate seabuckthorn seed oil, achieve controlled slow release, and possess long-term storage stability is of great practical significance for improving the application value and clinical efficacy of seabuckthorn seed oil. Summary of the Invention

[0006] In view of this, the purpose of this invention is to propose a sustained-release drug-loaded particle and its preparation method to solve the problems of poor stability and insufficient release control of thorn seed oil in traditional drug-loaded systems.

[0007] To achieve the above objectives, the present invention provides a method for preparing sustained-release drug-loaded particles, comprising the following steps:

[0008] S1: Add nanocellulose to N,N-dimethylformamide, sonicate for 1.5-2.5 h, then add sulfonyl chloride, heat to 55-65℃, stir and react for 10-14 h, centrifuge, wash, and obtain chlorinated nanocellulose;

[0009] S2: Chlorinated nanocellulose, lauryl diamine and laurylamine are added to N,N-dimethylformamide, heated to 125-135℃, stirred for 70-75h, cooled to 55-65℃, deionized water is added, stirred for 1.5-2.5h, centrifuged and vacuum dried to obtain aminated cross-linked nanocellulose.

[0010] S3: Add sodium alginate to deionized water, heat to 45-55℃, stir for 25-35 min, cool to 38-42℃, add sea buckthorn seed oil and emulsifier, stir at 11000-13000 rpm for 6-10 min, then add aminated cross-linked nanofibers, stir at 200-400 rpm for 25-35 min, freeze dry to obtain sustained-release drug-loaded particles.

[0011] Preferably, the preparation steps of the nanocellulose are as follows: microcrystalline cellulose is added to deionized water, then sulfuric acid and hydrochloric acid are added dropwise, and the mixture is stirred at room temperature for 10-14 hours. The temperature is then raised to 55-65°C, and the mixture is stirred for another 10-14 hours. The mixture is then dialyzed, transferred to a centrifuge tube, and centrifuged at 800-1200 rpm for 8-12 minutes. The supernatant is collected and vacuum dried to obtain nanocellulose.

[0012] Preferably, the average particle size of the microcrystalline cellulose is 60-70 μm.

[0013] Preferably, the weight ratio of the microcrystalline cellulose, deionized water, sulfuric acid and hydrochloric acid is 10:60-80:25-35:8-12.

[0014] Preferably, the molecular weight cutoff for dialysis is 100-500.

[0015] Preferably, in step S1, the weight ratio of nanocellulose, N,N-dimethylformamide and sulfonyl chloride is 0.5-1.5:15-25:0.05-0.2.

[0016] Preferably, in step S2, the weight ratio of chlorinated nanocellulose, lauryl diamine, laurylamine, N,N-dimethylformamide and deionized water is 0.5-1.5:0.08-0.25:0.03-0.1:15-25:15-45.

[0017] Preferably, in step S3, the weight ratio of sodium alginate, deionized water, and aminated cross-linked nanofibers is 1.5-2.5:60-100:0.5-1.5.

[0018] Preferably, the amount of sea buckthorn seed oil added in step S3 is 18%-22% of the total weight of sodium alginate and aminated cross-linked nanofibers.

[0019] Preferably, the emulsifier in step S3 is Tween 80.

[0020] Preferably, the amount of emulsifier added in step S3 is 8%-12% of the weight of sea buckthorn seed oil.

[0021] Preferably, the freeze-drying in step S3 is as follows: first pre-freezing at -50±5℃ for 5-7 hours, and then vacuum drying at -30±5℃ for 20-28 hours.

[0022] Furthermore, the present invention also provides a sustained-release drug-loaded particle, obtained by a method for preparing sustained-release drug-loaded particles.

[0023] The beneficial effects of this invention are:

[0024] This invention utilizes nanocellulose as the base material and undergoes specific chemical modifications to prepare a drug delivery system with ideal sustained-release properties. This system exhibits a three-stage release pattern: slow initial release, gradual increase in the middle stage, and a stable release in the later stage. This effectively maintains the effective drug concentration in the body, reduces the frequency of administration, and improves patient compliance and treatment efficacy.

[0025] This invention achieves precise control of the carrier structure at the molecular level through chlorination and amination crosslinking modification of nanocellulose. The nanoscale size endows the material with a larger specific surface area and reactivity, forming a more uniform and dense network structure, significantly improving the encapsulation efficiency and release control of drug molecules. This unique network structure can effectively regulate the diffusion behavior of drug molecules, avoiding the burst release phenomenon commonly found in traditional drug delivery systems.

[0026] This invention innovatively introduces long-chain alkylamines (lauryl diamine and laurylamine) as modifiers. These long-chain alkyl groups not only provide a hydrophobic microenvironment, enhancing the affinity for hydrophobic drugs such as sea buckthorn seed oil, but also form a complex spatial structure, increasing the tortuosity of the drug molecule diffusion path, thereby achieving precise control of release kinetics. The synergistic effect of lauryl diamine and laurylamine forms a network with appropriate hydrophobicity and porous structure, which can control the initial release without excessively inhibiting the later release, achieving an optimized balance throughout the release cycle. This balance is crucial for maintaining the long-term therapeutic effect of the drug.

[0027] The drug-loaded particles prepared by this invention exhibit excellent long-term stability, maintaining relatively stable release behavior even under accelerated testing conditions, providing reliable assurance for long-term storage and transportation of the product. This stability is attributed to the composite network structure formed by modified nanocellulose and sodium alginate, as well as the ionic or hydrogen bond interactions between the amino groups introduced during the amination process and sodium alginate.

[0028] In summary, this invention successfully solves the key technical problems of poor stability and insufficient release control of sea buckthorn seed oil in traditional drug delivery systems through precise chemical modification of nanocellulose and synergistic effects of multiple components. It provides new ideas and methods for developing efficient and stable sustained-release formulations of natural plant oils, and has broad application prospects and important practical value. Detailed Implementation

[0029] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments.

[0030] The microcrystalline cellulose used in this specific embodiment of the invention was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., with item number M489705-01 and an average particle size of 65 μm. The sodium alginate was also purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., with item number S278630.

[0031] Example 1:

[0032] (1) Add 10g of microcrystalline cellulose to 60g of deionized water, then add 25g of sulfuric acid and 8g of hydrochloric acid, stir at room temperature for 10h, then heat to 55℃ and continue stirring for 10h, then dialyze using a dialysis bag with a molecular weight cutoff of 100-500, continuously rinse with deionized water during dialysis until the pH is neutral, then transfer to a centrifuge tube and centrifuge at 800rpm for 8min, take the supernatant, vacuum dry to obtain nanocellulose;

[0033] (2) Add 0.5g of nanocellulose to 15g of N,N-dimethylformamide, disperse ultrasonically for 1.5h, then add 0.05g of sulfonyl chloride, heat to 55℃, stir and react for 10h, centrifuge, and wash three times with tetrahydrofuran to obtain chlorinated nanocellulose.

[0034] (3) Add 0.5g of chlorinated nanocellulose, 0.08g of lauryl diamine and 0.03g of lauryl amine to 15g of N,N-dimethylformamide, heat to 125℃, stir and react for 70h, cool to 55℃, add 15g of deionized water, stir for 1.5h, centrifuge, and vacuum dry to obtain amino-crosslinked nanocellulose.

[0035] (4) Add 1.5g sodium alginate to 60g deionized water, heat to 45℃, stir for 25min, cool to 38℃, add 0.4g sea buckthorn seed oil and 0.04g Tween 80, stir at 11000rpm for 6min, then add 0.5g aminated cross-linked nanofibers, stir at 200rpm for 25min, then pre-freeze at -45℃ for 5h, and vacuum dry at -25℃ for 20h to obtain sustained-release drug-loaded particles.

[0036] Example 2:

[0037] (1) Add 10g of microcrystalline cellulose to 70g of deionized water, then add 30g of sulfuric acid and 10g of hydrochloric acid, stir at room temperature for 12h, then heat to 60℃ and continue stirring for 12h, then dialyze using a dialysis bag with a molecular weight cutoff of 100-500, continuously rinse with deionized water during dialysis until the pH is neutral, then transfer to a centrifuge tube and centrifuge at 1000rpm for 10min, take the supernatant, vacuum dry to obtain nanocellulose;

[0038] (2) Add 1g of nanocellulose to 20g of N,N-dimethylformamide, sonicate for 2h, then add 0.1g of sulfonyl chloride, heat to 60℃, stir for 12h, centrifuge, and wash 3 times with tetrahydrofuran to obtain chlorinated nanocellulose;

[0039] (3) Add 1g of chlorinated nanocellulose, 0.15g of lauryl diamine and 0.05g of lauryl amine to 20g of N,N-dimethylformamide, heat to 130℃, stir for 72h, cool to 60℃, add 30g of deionized water, stir for 2h, centrifuge, and vacuum dry to obtain amino-crosslinked nanocellulose.

[0040] (4) Add 2g of sodium alginate to 80g of deionized water, heat to 50℃, stir for 30min, cool to 40℃, add 0.6g of sea buckthorn seed oil and 0.06g of Tween 80, stir at 12000rpm for 8min, then add 1g of amino-crosslinked nanofibers, stir at 300rpm for 30min, then pre-freeze at -50℃ for 6h, and vacuum dry at -30℃ for 24h to obtain sustained-release drug-loaded particles.

[0041] Example 3:

[0042] (1) Add 10g of microcrystalline cellulose to 80g of deionized water, then add 35g of sulfuric acid and 12g of hydrochloric acid, stir at room temperature for 14h, then heat to 65℃ and continue stirring for 14h, then dialyze using a dialysis bag with a molecular weight cutoff of 100-500, continuously rinsing with deionized water during dialysis until the pH is neutral, then transfer to a centrifuge tube and centrifuge at 1200rpm for 12min, take the supernatant, vacuum dry to obtain nanocellulose;

[0043] (2) Add 1.5g of nanocellulose to 25g of N,N-dimethylformamide, disperse ultrasonically for 2.5h, then add 0.2g of sulfonyl chloride, heat to 65℃, stir and react for 14h, centrifuge, and wash three times with tetrahydrofuran to obtain chlorinated nanocellulose;

[0044] (3) Add 1.5g of chlorinated nanocellulose, 0.25g of lauryl diamine and 0.1g of lauryl amine to 25g of N,N-dimethylformamide, heat to 135℃, stir for 75h, cool to 65℃, add 45g of deionized water, stir for 2.5h, centrifuge, and vacuum dry to obtain aminated cross-linked nanocellulose.

[0045] (4) Add 2.5g sodium alginate to 100g deionized water, heat to 55℃, stir for 35min, cool to 42℃, add 0.8g sea buckthorn seed oil and 0.08g Tween 80, stir at 13000rpm for 10min, then add 1.5g aminated cross-linked nanofibers, stir at 400rpm for 35min, then pre-freeze at 55℃ for 7h, and vacuum dry at -35℃ for 28h to obtain sustained-release drug-loaded particles.

[0046] Comparative Example 1:

[0047] The difference between Comparative Example 1 and Example 2 is that the nanocellulose in step (2) is replaced with microcrystalline cellulose;

[0048] The specific steps are as follows:

[0049] (1) Add 1g of microcrystalline cellulose to 20g of N,N-dimethylformamide, sonicate for 2h, then add 0.1g of sulfonyl chloride, heat to 60℃, stir for 12h, centrifuge, and wash 3 times with tetrahydrofuran to obtain chlorinated microcrystalline cellulose;

[0050] (2) Add 1g of chlorinated microcrystalline cellulose, 0.15g of lauryl diamine and 0.05g of lauryl amine to 20g of N,N-dimethylformamide, heat to 130℃, stir for 72h, cool to 60℃, add 30g of deionized water, stir for 2h, centrifuge, and vacuum dry to obtain aminated cross-linked microcrystalline cellulose.

[0051] (3) Add 2g of sodium alginate to 80g of deionized water, heat to 50℃, stir for 30min, cool to 40℃, add 0.6g of sea buckthorn seed oil and 0.06g of Tween 80, stir at 12000rpm for 8min, then add 1g of amino-crosslinked microcrystalline cellulose, stir at 300rpm for 30min, then pre-freeze at -50℃ for 6h, and vacuum dry at -30℃ for 24h to obtain drug-loaded particles.

[0052] Comparative Example 2:

[0053] The difference between Comparative Example 2 and Example 2 is that the aminated cross-linked nanofibers in step (4) are replaced with nanocellulose;

[0054] The specific steps are as follows:

[0055] (1) Add 10g of microcrystalline cellulose to 70g of deionized water, then add 30g of sulfuric acid and 10g of hydrochloric acid, stir at room temperature for 12h, then heat to 60℃ and continue stirring for 12h, then dialyze using a dialysis bag with a molecular weight cutoff of 100-500, continuously rinse with deionized water during dialysis until the pH is neutral, then transfer to a centrifuge tube and centrifuge at 1000rpm for 10min, take the supernatant, vacuum dry to obtain nanocellulose;

[0056] (2) Add 2g of sodium alginate to 80g of deionized water, heat to 50℃, stir for 30min, cool to 40℃, add 0.6g of sea buckthorn seed oil and 0.06g of Tween 80, stir at 12000rpm for 8min, then add 1g of nanocellulose, stir at 300rpm for 30min, then pre-freeze at -50℃ for 6h, and vacuum dry at -30℃ for 24h to obtain drug-loaded particles.

[0057] Comparative Example 3:

[0058] The difference between Comparative Example 3 and Example 2 is that lauryl diamine in step (3) is replaced with ethylenediamine;

[0059] The specific steps are as follows:

[0060] (1) Add 10g of microcrystalline cellulose to 70g of deionized water, then add 30g of sulfuric acid and 10g of hydrochloric acid, stir at room temperature for 12h, then heat to 60℃ and continue stirring for 12h, then dialyze using a dialysis bag with a molecular weight cutoff of 100-500, continuously rinse with deionized water during dialysis until the pH is neutral, then transfer to a centrifuge tube and centrifuge at 1000rpm for 10min, take the supernatant, vacuum dry to obtain nanocellulose;

[0061] (2) Add 1g of nanocellulose to 20g of N,N-dimethylformamide, sonicate for 2h, then add 0.1g of sulfonyl chloride, heat to 60℃, stir for 12h, centrifuge, and wash 3 times with tetrahydrofuran to obtain chlorinated nanocellulose;

[0062] (3) Add 1g of chlorinated nanocellulose, 0.15g of ethylenediamine and 0.05g of laurylamine to 20g of N,N-dimethylformamide, heat to 130℃, stir for 72h, cool to 60℃, add 30g of deionized water, stir for 2h, centrifuge, and vacuum dry to obtain amino-crosslinked nanocellulose.

[0063] (4) Add 2g of sodium alginate to 80g of deionized water, heat to 50℃, stir for 30min, cool to 40℃, add 0.6g of sea buckthorn seed oil and 0.06g of Tween 80, stir at 12000rpm for 8min, add 1g of amino-crosslinked nanofibers, stir at 300rpm for 30min, pre-freeze at -50℃ for 6h, and vacuum dry at -30℃ for 24h to obtain drug-loaded particles.

[0064] Comparative Example 4:

[0065] The difference between Comparative Example 4 and Example 2 is that laurylamine in step (3) is replaced with lauryl diamine;

[0066] The specific steps are as follows:

[0067] (1) Add 10g of microcrystalline cellulose to 70g of deionized water, then add 30g of sulfuric acid and 10g of hydrochloric acid, stir at room temperature for 12h, then heat to 60℃ and continue stirring for 12h, then dialyze using a dialysis bag with a molecular weight cutoff of 100-500, continuously rinse with deionized water during dialysis until the pH is neutral, then transfer to a centrifuge tube and centrifuge at 1000rpm for 10min, take the supernatant, vacuum dry to obtain nanocellulose;

[0068] (2) Add 1g of nanocellulose to 20g of N,N-dimethylformamide, sonicate for 2h, then add 0.1g of sulfonyl chloride, heat to 60℃, stir for 12h, centrifuge, and wash 3 times with tetrahydrofuran to obtain chlorinated nanocellulose;

[0069] (3) Add 1g of chlorinated nanocellulose and 0.2g of lauryl diamine to 20g of N,N-dimethylformamide, heat to 130℃, stir for 72h, cool to 60℃, add 30g of deionized water, stir for 2h, centrifuge, and vacuum dry to obtain amino-crosslinked nanocellulose.

[0070] (4) Add 2g of sodium alginate to 80g of deionized water, heat to 50℃, stir for 30min, cool to 40℃, add 0.6g of sea buckthorn seed oil and 0.06g of Tween 80, stir at 12000rpm for 8min, add 1g of amino-crosslinked nanofibers, stir at 300rpm for 30min, pre-freeze at -50℃ for 6h, and vacuum dry at -30℃ for 24h to obtain drug-loaded particles.

[0071] Performance testing:

[0072] In vitro sustained-release performance test: The dynamic dialysis method was used. 100 mg of drug-loaded particles were loaded into a dialysis bag with a molecular weight cutoff of 8000 and placed in 500 mL of release medium (37℃ PBS pH 7.4 + 0.1% Tween 80). The temperature was maintained at 100 rpm with a magnetic stirrer. 5 mL samples were taken at regular intervals (with an equal amount of fresh medium added at the same time). The test was conducted continuously for 72 h. The release rate of quercetin in sea buckthorn seed oil at 1 h, 24 h and 72 h was detected by HPLC. The results are shown in Table 1.

[0073] Accelerated test: The samples were stored at 40℃±2℃ / 75%RH±5% for 6 months to conduct in vitro sustained-release performance tests. The results are shown in Table 2.

[0074] Table 1 Results of in vitro sustained-release performance test

[0075]

[0076] Table 2 Results of in vitro sustained-release performance test after accelerated test

[0077]

[0078] Data Analysis:

[0079] As can be seen from the data in Examples 1-3 in Tables 1-2, the sustained-release drug-loaded particles prepared by this invention exhibit good sustained-release performance and long-term stability. By using nanocellulose as a crosslinking agent and modifying it through chlorination and amination, the resulting drug-loaded system demonstrates ideal drug release control. The drug release curve shows a slow release initially, a gradual increase in the middle stage, and a tendency to stabilize in the later stage. This release pattern may be attributed to the multiple interactions between the modified nanocellulose and the drug. Furthermore, after accelerated testing, the drug-loaded system still maintains relatively stable release behavior, indicating that the system has good long-term storage stability, which is of great significance for practical applications.

[0080] As can be seen from the data in Tables 1-2 for Example 2 and Comparative Example 1, replacing microcrystalline cellulose with nanocellulose can significantly improve the drug release control capability of the sustained-release drug delivery system. The release rate of Example 2 at all time points was lower than that of Comparative Example 1, and the release behavior after accelerated testing showed little change. This difference may be attributed to the larger specific surface area and higher reactivity of nanocellulose, which allows it to form a more uniform and stable modified structure during chlorination and amination crosslinking reactions. Furthermore, the nanoscale size may contribute to the formation of a denser network structure, improving the encapsulation efficiency and release control capability of drug molecules.

[0081] As can be seen from the data in Tables 1-2 for Example 2 and Comparative Example 2, replacing ordinary cellulose nanofibers with aminated cross-linked nanofibers can significantly improve the sustained-release performance of drug-loaded particles. Comparative Example 2 released a large amount of drug initially, with near-complete release after 24 hours, while Example 2 exhibited an ideal gradual release behavior. This difference may stem from the fact that the functional groups introduced during the aminated cross-linking process alter the physicochemical properties of the cellulose surface, forming a three-dimensional network with specific pore sizes. This network can effectively regulate the diffusion behavior of drug molecules. Furthermore, the amino groups introduced during the aminated process interact with sodium alginate through ionic or hydrogen bond interactions, further enhancing the structural stability of the carrier. After accelerated testing, the early release rate of Comparative Example 2 increased significantly, while that of Example 2 remained essentially stable, indicating that the aminated cross-linked structure helps resist changes in the external environment and maintain the long-term stability of the carrier.

[0082] As can be seen from the data in Tables 1-2 for Example 2 and Comparative Example 3, lauryl diamine significantly improves the drug release control capability of the sustained-release drug delivery system compared to ethylenediamine. The release rate of Example 2 at all time points was significantly lower than that of Comparative Example 3, and the release behavior after accelerated testing showed little change. This difference may be attributed to the longer alkyl chain of lauryl diamine, which provides stronger hydrophobic interactions and enhances the affinity between the modified nanocellulose and hydrophobic drug molecules. The longer alkyl chain may also form a more complex spatial structure, increasing the tortuosity of the drug molecule diffusion path and thus slowing down the release rate. Furthermore, lauryl diamine may form a more uniform and stable cross-linked network with the surface of nanocellulose, reducing the formation of localized high-release regions.

[0083] As can be seen from the data in Tables 1-2 for Example 2 and Comparative Example 4, the combined use of lauryl diamine and laurylamine has a significant impact on the drug release behavior of the sustained-release drug delivery system. Comparative Example 4, using only lauryl diamine as a modifier, showed a significantly lower release rate than Example 2 throughout the entire test period, particularly exhibiting significant under-release during the long-term release phase (72 hours). This difference may stem from the fact that a single modifier cannot provide optimal surface properties and spatial structure. The synergistic effect of lauryl diamine and laurylamine may have formed a network structure with appropriate hydrophobicity and porosity, which can form sufficiently strong interactions with drug molecules to control initial release without excessively inhibiting later release. After accelerated testing, the release rate of Comparative Example 4 decreased significantly, suggesting that excessive cross-linking may lead to structural changes in the system during long-term storage, affecting the diffusion and release of drug molecules, while Example 2 maintained relatively stable release behavior.

[0084] Those skilled in the art should understand that the discussion of any of the above embodiments is merely exemplary and is not intended to imply that the scope of the invention is limited to these examples; within the framework of the invention, the technical features of the above embodiments or different embodiments can also be combined, the steps can be implemented in any order, and there are many other variations of the different aspects of the invention as described above, which are not provided in detail for the sake of brevity.

Claims

1. A method for preparing sustained-release drug-loaded particles, characterized in that, Includes the following steps: S1: Add nanocellulose to N,N-dimethylformamide, sonicate for 1.5-2.5 h, then add sulfonyl chloride, heat to 55-65℃, stir and react for 10-14 h, centrifuge, wash, and obtain chlorinated nanocellulose; S2: Chlorinated nanocellulose, lauryl diamine and laurylamine are added to N,N-dimethylformamide, heated to 125-135℃, stirred for 70-75h, cooled to 55-65℃, deionized water is added, stirred for 1.5-2.5h, centrifuged and vacuum dried to obtain aminated cross-linked nanocellulose. S3: Add sodium alginate to deionized water, heat to 45-55℃, stir for 25-35 min, cool to 38-42℃, add sea buckthorn seed oil and emulsifier, stir at 11000-13000 rpm for 6-10 min, then add aminated cross-linked nanofibers, stir at 200-400 rpm for 25-35 min, freeze dry to obtain sustained-release drug-loaded particles; In step S1, the weight ratio of nanocellulose, N,N-dimethylformamide, and sulfonyl chloride is 0.5-1.5:15-25:0.05-0.

2. In step S2, the weight ratio of chlorinated nanocellulose, lauryl diamine, laurylamine, N,N-dimethylformamide, and deionized water is 0.5-1.5:0.08-0.25:0.03-0.1:15-25:15-45. In step S3, the weight ratio of sodium alginate, deionized water, and aminated cross-linked nanofibers is 1.5-2.5:60-100:0.5-1.

5. The preparation steps of the nanocellulose are as follows: microcrystalline cellulose is added to deionized water, then sulfuric acid and hydrochloric acid are added dropwise, and the mixture is stirred at room temperature for 10-14 h. The temperature is then raised to 55-65℃, and the mixture is stirred for another 10-14 h. The mixture is then dialyzed, transferred to a centrifuge tube, and centrifuged at 800-1200 rpm for 8-12 min. The supernatant is collected and vacuum dried to obtain nanocellulose. In step S3, the amount of sea buckthorn seed oil added is 18%-22% of the total weight of sodium alginate and amino-crosslinked nanofibers; In step S3, the emulsifier is Tween 80, and the amount of emulsifier added is 8%-12% of the weight of sea buckthorn seed oil. In step S3, the freeze-drying process involves pre-freezing at -50±5℃ for 5-7 hours, followed by vacuum drying at -30±5℃ for 20-28 hours.

2. The method for preparing sustained-release drug-loaded particles according to claim 1, characterized in that, The average particle size of the microcrystalline cellulose is 60-70 μm.

3. The method for preparing sustained-release drug-loaded particles according to claim 1, characterized in that, The weight ratio of the microcrystalline cellulose, deionized water, sulfuric acid, and hydrochloric acid is 10:60-80:25-35:8-12.

4. The method for preparing sustained-release drug-loaded particles according to claim 1, characterized in that, The molecular weight cutoff for the dialysis is 100-500.

5. A sustained-release drug-loaded particle, characterized in that, It is obtained by the method for preparing sustained-release drug-loaded particles according to any one of claims 1-4.

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