Drug carrier for suppurative arthritis and preparation method thereof
Patent Information
- Application Number
- CN202610358394.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-03-23
- Publication Date
- 2026-05-12
AI Technical Summary
Existing technologies lack intelligent response systems for septic arthritis, gallium ion delivery is not targeted enough, and there are no antibiotic synergistic drug delivery strategies, making it difficult for antibacterial drugs to penetrate macrophage membranes to kill intracellular bacteria. Furthermore, there is a lack of biocompatible and efficient drug delivery systems suitable for pediatric patients.
A drug carrier comprising liquid metal nanoparticles, a mesoporous material shell, and a hyaluronic acid-modified layer was designed. By targeting and recognizing the CD44 receptor, it utilizes the inflammatory microenvironment to release Ga3+ and antibiotics, thereby achieving a synergistic effect of multiple antibacterial mechanisms.
It achieves targeted enrichment, intelligent release, and synergistic antibacterial effects of drugs, reduces drug resistance, and improves the treatment effect of pyogenic arthritis, making it particularly suitable for pediatric patients.
Smart Images
Figure CN122005853A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of drug carrier technology, specifically to a drug carrier for suppurative arthritis and its preparation method. Background Technology
[0002] Suppurative arthritis (SA) is a common acute infectious disease in orthopedics, with a high incidence and disability rate in children. Epidemiological studies show that SA accounts for 21% of all bone and joint infections in children, with Staphylococcus aureus being the most prevalent pathogen, accounting for 85%.
[0003] The lack of intelligent response systems targeting the pathological features of SA in existing technologies is mainly due to the presence of a characteristic pathological microenvironment within the joint cavity of SA: overexpression of hyaluronidase (HAase), with concentrations reaching 10-100 times the normal level; an acidic pH environment, where lactic acid accumulation lowers the pH of the synovial fluid to 6.0-6.8; and high expression of CD44 receptors on macrophages, with expression increasing 3-5 times under inflammatory stimulation.
[0004] Meanwhile, existing technologies lack efficient and safe antibacterial metal ion delivery systems. Gallium ions (Ga ions) 3+ Gallium nitrate possesses a unique antibacterial mechanism, interfering with bacterial iron metabolism through an "iron mimicry" strategy, making it less likely to induce bacterial resistance and exhibiting good biocompatibility (the FDA has approved gallium nitrate for clinical use). However, in existing technologies, free Ga... 3+ With a short half-life in vivo (less than 30 minutes), it lacks the ability to encode Ga... 3+ A vector system that targets and delivers the contents of an infected site, and is free of Ga. 3+ Optimized regimens for co-administration with antibiotics.
[0005] Therefore, existing technologies face core technical challenges: how to enable antibacterial drugs to effectively penetrate macrophage membranes and kill latent intracellular bacteria to reduce the recurrence rate of SA; how to design systems with multiple antibacterial mechanisms to reduce the emergence of drug-resistant bacteria and improve efficacy against drug-resistant bacteria such as MRSA; and how to construct a drug delivery system with high biocompatibility and low toxicity suitable for long-term use in pediatric patients. Summary of the Invention
[0006] The purpose of this invention is to provide a drug carrier for suppurative arthritis and a method for preparing the same, in order to solve at least one technical problem existing in the prior art.
[0007] A first aspect of the present invention provides a drug carrier for suppurative arthritis, comprising:
[0008] Liquid metal nanoparticles, wherein the liquid metal is gallium (Ga), gallium-indium alloy (GaIn), or ternary or multi-element alloys containing gallium, indium, and tin;
[0009] The mesoporous material shell coating the liquid metal nanoparticles, wherein the mesoporous material is at least one of mesoporous silica, mesoporous titanium dioxide, and mesoporous carbon; and
[0010] A hyaluronic acid-modified layer covering the mesoporous material shell.
[0011] In this invention, liquid metal nanoparticles serve as the core, functioning firstly as a physical support and delivery carrier for the entire system, and secondly as a source of antibacterial Ga ions. 3+ The liquid metal nanoparticle core, acting as a reservoir, undergoes hydrolysis within the inflammatory, acidic microenvironment of the joint cavity, continuously and controllably releasing Ga. 3+ This allows it to exert its unique "iron competition" antibacterial effect. The outer surface of the liquid metal nanoparticles is completely covered by an intermediate layer (mesoporous material shell), forming a stable core-shell interface that prevents the aggregation and premature leakage of the liquid metal. The core degradation kinetics are directly regulated by the response of the outer structure to the microenvironment (such as pH reduction).
[0012] A mesoporous material shell coats the core of liquid metal nanoparticles, forming an inorganic shell with uniform nanopores (mesoporosis). Its functions are twofold: first, during the loading phase, it utilizes its high specific surface area and pore volume to load large quantities of antibiotic molecules (such as clindamycin) through physical adsorption or capillary action; second, during the release phase, its pores serve as channels for drug diffusion, and its surface can act as anchoring points for the outer hyaluronic acid modification. This mesoporous material shell is tightly attached to the liquid metal nanoparticle core through chemical bonds (e.g., Si-OM, where M is a metal) and physical interactions. The pore size and surface chemical properties of the shell determine the antibiotic loading capacity and release rate.
[0013] The hyaluronic acid-modified layer covers the outer surface of the mesoporous material shell through chemical bonding (such as amide bonds and silyl ester bonds) or strong physical adsorption (such as electrostatic / hydrogen bonding), forming a hydrophilic "coat" whose core functions are "smart switch" and "navigation beacon." On the one hand, the hyaluronic acid-modified layer realizes the enzyme-responsive switching function: as a substrate of hyaluronidase (HAase), it is specifically degraded in the high-concentration HAase environment of infected joints, thereby removing the outer barrier and triggering the rapid release of internal drugs. On the other hand, the hyaluronic acid-modified layer realizes the active targeting navigation function: as a natural ligand of the CD44 receptor, it can specifically recognize and bind to the CD44 receptor highly expressed on the surface of the synovial membrane and infiltrating macrophages, realizing the active enrichment and internalization of nanoparticles into lesions and target cells. The integrity of the hyaluronic acid-modified layer determines the closed state of the drug in the mesopores of the intermediate layer (mesoporous material shell), and its degradation is a key step in initiating the drug "burst release." At the same time, the targeting ligands on its surface determine the in vivo distribution and cellular uptake pathway of the entire nanoparticle.
[0014] The drug carrier of the present invention, through the precise combination of the above three-layer structure, can achieve:
[0015] (1) Targeting and enrichment: After intravenous or intra-articular injection, the outer layer of hyaluronic acid (HA) plays a "navigation" function. By binding to CD44 receptors that are highly expressed at the site of inflammation, the nanoparticles are actively enriched in the synovial membrane and around macrophages and are actively internalized by the cells.
[0016] (2) Intelligent response and drug release: In the infected joint cavity, the outer HA layer is degraded by highly active HAase, which disrupts the drug sealing effect of the surface on the mesopores of the middle layer; at the same time, the local acidic environment (pH ~6.5) caused by inflammation triggers the hydrolysis of the liquid metal core, releasing Ga 3+ The removal of the outer barrier allows drugs loaded in the mesopores of the middle layer (such as clindamycin) to diffuse and be released rapidly through the concentration gradient.
[0017] (3) Synergistic antibacterial effect: The released drug (such as clindamycin) reacts with Ga 3+ Both form high local concentrations at the lesion site and exert their effects through different antibacterial mechanisms (clindamycin inhibits protein synthesis, Ga...). 3+ (Interfering with iron metabolism) synergistically achieves multi-level and all-round attack on planktonic bacteria, biofilm bacteria, and intracellular bacteria killed by drugs released from nanoparticles that have been internalized by macrophages, thereby eradicating the infection.
[0018] The drug carrier of the present invention can be used to load different types of therapeutic agents (drugs) such as antibiotics (e.g., clindamycin), anti-inflammatory drugs, and anti-tumor drugs, and the therapeutic agents can enter the mesoporous shell of the mesoporous material.
[0019] Furthermore, the liquid metal is pure gallium (Ga), which is processed by controlling the temperature to be slightly above its melting point (29.8°C).
[0020] Further, the liquid metal is a gallium-indium alloy (GaIn), wherein the mass percentage of indium is 10%-25% (e.g., 16%); this alloy is liquid at room temperature, has moderate surface tension, and is easily dispersed into nanoparticles by ultrasound. Preferably, the mass percentage of indium in the gallium-indium alloy is 16%.
[0021] Furthermore, the liquid metal is a ternary or multi-element alloy containing gallium, indium, and tin, in order to further adjust its melting point, rheological properties, or degradation rate.
[0022] Furthermore, the particle size of the liquid metal nanoparticles is 50 nm - 200 nm. Preferably, the particle size of the liquid metal nanoparticles is 80 nm - 150 nm. The particle size of the liquid metal nanoparticles can be controlled by controlling the ultrasonic power and time.
[0023] Further, the thickness of the mesoporous material shell is 10 nm - 30 nm, and the pore size is 2 nm - 5 nm. Preferably, the thickness of the mesoporous material shell is 15 nm - 25 nm.
[0024] Furthermore, the mesoporous material shell is a composite shell with a multi-layered structure. Preferably, the mesoporous material shell is a composite shell with an inner layer and an outer layer, wherein the inner layer is dense silica to ensure sealing, and the outer layer is mesoporous silica to achieve high drug loading.
[0025] Furthermore, the hyaluronic acid modified layer is replaced with a biopolymer that can be degraded by enzymes specific to the inflammatory site (such as matrix metalloproteinases (MMPs), phospholipases, etc.). Preferably, the hyaluronic acid modified layer is replaced with gelatin (which can be degraded by MMPs), polypeptides containing specific enzyme cleavage sequences, etc.
[0026] Furthermore, the hyaluronic acid modified layer is replaced with a molecular layer with targeting function, such as a ligand capable of binding to receptors highly expressed at sites of inflammation or infection. Preferably, the hyaluronic acid modified layer is replaced with an RGD peptide (targeting integrin) layer, a mannose (targeting macrophage mannose receptor) layer, etc.
[0027] Furthermore, the hyaluronic acid modified layer is replaced with a hyaluronic acid co-modified layer containing molecules with targeting function.
[0028] Further, the hyaluronic acid has a molecular weight of 5 kDa-500 kDa, and the modification density (mass ratio) is 5%-20% of the total mass of the drug carrier with the intact structure. Preferably, the hyaluronic acid has a molecular weight of 10 kDa-100 kDa.
[0029] A second aspect of the present invention provides a method for preparing a drug carrier for suppurative arthritis, comprising the following steps:
[0030] Liquid metal, PVP and the first solvent were mixed, ultrasonicated, and centrifuged to disperse the precipitate in water to obtain LMP stock solution.
[0031] LMP stock solution, second solvent, ammonia, and CTAB were mixed at 20℃-50℃, and TEOS was added dropwise. After the reaction, LMP@MSN was obtained.
[0032] HA was dissolved in a third solvent, and EDC and NHS were added sequentially. The mixture was activated at room temperature. The activated HA solution was then added dropwise to the PBS dispersion of LMP@MSN. The mixture was stirred in the dark to obtain a drug carrier for septic arthritis.
[0033] Furthermore, the method for preparing the drug carrier for suppurative arthritis specifically includes the following steps:
[0034] Liquid metal and PVP were added to an alcohol-water mixture, and the mixture was ultrasonically treated in an ice-water bath. The precipitate was collected by centrifugation and dispersed in water to obtain LMP stock solution.
[0035] LMP stock solution, ethanol, ammonia, and CTAB were mixed at 25℃-35℃, and TEOS was added dropwise. After the reaction, LMP@MSN was obtained.
[0036] HA was dissolved in MES buffer, and EDC and NHS were added sequentially. The mixture was activated at room temperature. The activated HA solution was then added dropwise to the PBS dispersion of LMP@MSN and stirred in the dark to obtain a drug carrier for septic arthritis.
[0037] Furthermore, the mesoporous silica shell is formed by growing on the surface of liquid metal particles under alkaline conditions using a sol-gel method with hexadecyltrimethylammonium bromide (CTAB) as a template agent and tetraethyl orthosilicate (TEOS) as a silicon source.
[0038] Furthermore, in order to enhance drug loading or achieve co-loading, functional elements (such as calcium and strontium) can be co-doped during the synthesis of mesoporous shells, or the inner surface of the mesoporous shells can be modified with functional groups such as amino (-NH2) and carboxyl (-COOH) groups to load drugs through chemical bonds.
[0039] Furthermore, hyaluronic acid was modified onto the surface of an aminated mesoporous silica shell via an amidation reaction. Specifically, the MSN surface was first aminated using aminopropyltriethoxysilane (APTES), and then the carboxyl groups of the hyaluronic acid were activated using 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), causing them to react with the amino groups on the shell surface to form stable amide bonds.
[0040] The technical solutions of the embodiments of the present invention have the following beneficial effects:
[0041] 1. Achieve active targeting: By targeting the CD44 receptor with hyaluronic acid, the drug can be precisely concentrated at the lesion, increasing local concentration and reducing systemic side effects;
[0042] 2. Dual intelligent drug release: Based on the dual enzyme and pH response of the pathological microenvironment, the drug release is spatially and temporally controlled, improving utilization efficiency;
[0043] 3. Synergistic antibacterial effect: Through the co-delivery and synergistic effect of antibiotics and gallium ions, it effectively overcomes drug resistance and eradicates intracellular bacterial infections, reducing the recurrence rate;
[0044] 4. High biocompatibility: All core materials have good biocompatibility and clinical safety, making them especially suitable for pediatric patients;
[0045] 5. Platform-based design: It adopts a modular "core-shell-coating" structure, providing a general technology platform for the development of a series of multifunctional nanomedicines. Attached Figure Description
[0046] Figure 1 The images show the infrared spectra of different substances in the embodiments of the present invention, where (a), (b), and (c) are the infrared spectra of LMP nanoparticles, LMP@MSN-NH2 nanoparticles, and LMP@MSN / DA@HA nanoparticles, respectively.
[0047] Figure 2 These are ultraviolet absorption spectra or standard curves of different substances in the embodiments of the present invention, wherein A, B, and C are the ultraviolet absorption spectrum of 50 μg / mL clindamycin, the standard curve of clindamycin at 199 nm, and the ultraviolet absorption spectrum of LMP@MSN / DA@HA, respectively.
[0048] Figure 3 The figures are statistical charts of DLS test results for different substances in the embodiments of the present invention, where A is a statistical chart of DLS test results for LMP@MSN@HA in aqueous solution, and B is a statistical chart of DLS test results for LMP@MSN / DA@HA in aqueous solution.
[0049] Figure 4 This is a morphology diagram of the LMP@MSN@HA nanoparticles in an embodiment of the present invention.
[0050] Figure 5 This is the EDS spectrum of LMP@MSN / DA@HA in an embodiment of the present invention.
[0051] Figure 6 This is the drug release curve of LM@MSN / DA@HA in an embodiment of the present invention.
[0052] Figure 7 This is a statistical chart of cell survival rate in an embodiment of the present invention.
[0053] Figure 8 This is a diagram showing the results of Calcein-AM / PI live / dead staining in an embodiment of the present invention.
[0054] Figure 9 This is a diagram showing the antibacterial experiment results in an embodiment of the present invention. Detailed Implementation
[0055] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.
[0056] Example 1: Preparation of LMP@MSN / DA@HA nano-drug delivery system
[0057] 1. Preparation of liquid metal nanoparticles (LMP)
[0058] 0.5 g of gallium-indium alloy (Ga:In = 84:16, wt%) was added to 20 mL of an ethanol / water (v / v = 1:1) mixed solution containing 1% (w / v) polyvinylpyrrolidone (PVP K30, 0.2 g). The mixture was placed in an ice-water bath and sonicated for 30 minutes using an ultrasonic cell disruptor at a power of 400 W and a cycle (pulse on / off time) of 5 s / 5 s. The resulting gray suspension was centrifuged at 5000 rpm for 10 minutes, the precipitate was collected, washed three times with deionized water, and redispersed in 20 mL of deionized water to obtain an LMP dispersion (concentration approximately 25 mg / mL).
[0059] 2. Preparation of LMP@MSN, i.e., coating liquid metal nanoparticles with a mesoporous material shell.
[0060] Take 5 mL of the above LMP dispersion and add 30 mL of anhydrous ethanol, 1.5 mL of concentrated ammonia (28%), and 0.1 g of cetyltrimethylammonium bromide (CTAB) sequentially. Stir magnetically (500 rpm) in a 30°C water bath for 30 minutes to ensure homogeneity. Then, slowly add 0.3 mL of tetraethyl orthosilicate (TEOS) at a rate of 0.5 mL / min using a micro-injection pump. After the addition is complete, continue to gently stir the reaction at 30°C for 6 hours. After the reaction is complete, centrifuge the product at 10,000 rpm for 15 minutes and wash three times each with ethanol and deionized water. To remove the CTAB template, disperse the precipitate in 50 mL of acidic ethanol (ethanol solution containing 1% concentrated hydrochloric acid) and reflux extract at 60°C for 24 hours. Finally, centrifuge, wash, and vacuum dry to obtain powdered LMP@MSN.
[0061] 3. Preparation of LMP@MSN / DA, i.e., loading with the antibiotic clindamycin (DA)
[0062] 20 mg LMP@MSN was dispersed in 10 mL of phosphate-buffered saline (PBS, 0.01 M, pH 7.4), and 1 mL of methanol solution containing 5 mg clindamycin (DA, clindamycin phosphate) was added. The mixture was loaded at 200 rpm for 24 hours under light-protected conditions at 25°C. After loading, the mixture was centrifuged at 12000 rpm for 20 minutes to collect the precipitate (i.e., drug-loaded nanoparticles). The precipitate was gently washed twice with PBS to remove the drug adsorbed on the surface. The supernatant and washing solution were combined, and the amount of unloaded drug was determined by high-performance liquid chromatography (HPLC). The drug loading (DL) and encapsulation efficiency (EE) were calculated. The precipitate was dispersed in PBS for later use.
[0063] The calculated drug loading is approximately 12.5 wt%, and the encapsulation efficiency is approximately 85%.
[0064] 4. Preparation of LMP@MSN / DA@HA, i.e., surface-modified hyaluronic acid (HA)
[0065] 10 mg of hyaluronic acid (HA, MW=50 kDa) was dissolved in 5 mL of MES buffer (0.1 M, pH 5.5), followed by the addition of 20 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 10 mg of N-hydroxysuccinimide (NHS). The reaction was activated at room temperature for 30 minutes. The activated HA solution was then added dropwise to 10 mL of PBS (pH 7.4) suspension containing 20 mg of LMP@MSN / DA (based on the carrier). The mixture was stirred at 25 °C in the dark for 12 hours. The reaction solution was then transferred to a dialysis bag with a molecular weight cutoff of 100 kDa and dialyzed against ultrapure water for 24 hours to completely remove unreacted HA and chemical reagents. Finally, the product in the dialysis bag was freeze-dried to obtain a white flocculent solid LMP@MSN / DA@HA powder (i.e., a drug carrier loaded with DA for septic arthritis).
[0066] Comparative Example 1: Preparation of LMP@MSN / DA@HA
[0067] Comparative Example 1 is basically the same as Example 1, except that it does not contain the antibiotic clindamycin (DA), and the final product is LMP@MSN@HA powder.
[0068] Comparative Example 2: Preparation of LMP@MSN-NH2
[0069] Comparative Example 2 is basically the same as Example 1, except that it does not contain the antibiotic clindamycin (DA) and is not modified with hyaluronic acid on the surface, thus obtaining LMP@MSN-NH2 powder.
[0070] The final products obtained from the examples and comparative examples are characterized below, and their key performance is verified.
[0071] 1. Morphological and structural characterization
[0072] Figure 1 The infrared spectra of LMP, LMP@MSN-NH2, and LMP@MSN / DA@HA are shown below. It can be seen that the infrared spectrum of LMP@MSN / DA@HA has a new absorption vibration peak, indicating the successful preparation of the drug-loaded system.
[0073] Figure 2 In the images, A, B, and C represent the UV absorption spectrum of 50 μg / mL clindamycin, the standard curve of clindamycin at 199 nm, and the UV absorption spectrum of LMP@MSN / DA@HA, respectively. It can be seen that LMP@MSN / DA@HA successfully loaded the drug (clindamycin).
[0074] Figure 3 Figures A and B show the dynamic light scattering (DLS) test results of LMP@MSN@HA and LMP@MSN / DA@HA in aqueous solution, respectively. It can be seen that the average particle size of LMP@MSN / DA@HA is 452 nm, while the average particle size of LMP@MSN@HA without drug loading is 396 nm, which is smaller than that of LMP@MSN / DA@HA. This further proves the successful loading of the nanomedicine clindamycin, and its smaller nanoparticle size is beneficial to its biological application.
[0075] Figure 4 The scanning electron microscope (SEM) image of LMP@MSN@HA shows that the LMP@MSN@HA sample exhibits a clear "core-shell" structure. The liquid metal core (dark color) is completely covered by a uniform mesoporous silica shell (light color). The overall particle size distribution is uniform, and the structure is spherical with an average diameter of about 400 nm, which is consistent with the DLS results. Its good biocompatibility and small nanoscale size are beneficial to its bioavailability.
[0076] Figure 5 The EDS spectrum of LMP@MSN / DA@HA shows that LMP@MSN / DA@HA is mainly composed of C, N, O, Ga, and In elements.
[0077] 2. Validation of intelligent drug release performance
[0078] LMP@MSN / DA@HA was placed in PBS containing different concentrations of hyaluronidase (0 mg / mL, 0.15 mg / mL, 0.3 mg / mL, 0.6 mg / mL HAase), and the release of DA was measured. Figure 6As shown, under the action of 0.6 mg / mL HAase, the cumulative release rate of DA reached more than 85% within 48 hours, which is much higher than the 25% of the enzyme-free group, demonstrating the significant enzyme response characteristics of LMP@MSN / DA@HA.
[0079] Ga was monitored in buffer solutions at pH 7.4 and pH 6.5. 3+ Release, results showed that Ga was released within 72 hours under pH 6.5 conditions. 3+ The cumulative release was approximately three times that under pH 7.4 conditions, demonstrating the excellent acid responsiveness of LMP@MSN / DA@HA.
[0080] 3. In vitro biological function verification
[0081] Different concentrations of hapase (12.5 μg / mL, 25 μg / mL, 50 μg / mL, 100 μg / mL, 200 μg / mL) were co-cultured with RAW cells for one day, and then detected with CCK8 reagent. The results were compared with the negative control group. Figure 7 As shown, the cell survival rate of each group is around 100%, indicating that HAase has good biocompatibility at this concentration.
[0082] Different concentrations of HAase (0 μg / mL, 25 μg / mL, 50 μg / mL, 100 μg / mL, 200 μg / mL) were co-cultured with RAW cells for one day, followed by Calcein-AM / PI live / dead cell staining (green for live cells, red for dead cells), and compared with the negative control group. Results are as follows... Figure 8 As shown, HAase exhibits good biocompatibility at different concentrations.
[0083] After diluting LMP@MSN / DA@HA nanoparticles to different concentrations, the intact nanoparticle solution was added to each well of a 96-well plate. Then, an equal volume of Staphylococcus aureus bacterial suspension (2×10^6 CFU / mL in LB) was added, and a positive control and a negative control were set up. The plates were incubated at 37°C in a shaker for 18 hours. After 18 hours of incubation, the absorbance (OD) of the samples was measured using a microplate reader. 600 The MIC (Microbiological Inhibition Concentration) value is defined as the lowest concentration of a compound at which bacterial growth is completely inhibited. After determining the MIC, bacterial suspensions treated with different methods are inoculated onto LB agar plates. After incubation at 37°C for 15–18 hours, the MBC (Microbiological Compatibility Concentration) value is defined as the lowest concentration at which no colony formation is observed. Figure 9 As shown, when different concentrations of HAase were added to a 10^5 CFU / mL Staphylococcus aureus solution, the antibacterial effect of HAase gradually increased with increasing concentration, reaching the minimum inhibitory concentration at 500 μg / mL.
[0084] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any form or substance. It should be noted that those skilled in the art can make various improvements and additions without departing from the method of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention. Any modifications, alterations, and equivalent changes made by those skilled in the art based on the above-disclosed technical content without departing from the spirit and scope of the present invention are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, and evolutions made to the above embodiments based on the essential technology of the present invention still fall within the scope of the technical solution of the present invention.
Claims
1. A drug carrier for suppurative arthritis, characterized in that, include: Liquid metal nanoparticles, wherein the liquid metal is gallium, gallium-indium alloy, or ternary or multi-element alloy containing gallium, indium, and tin; The mesoporous material shell coating the liquid metal nanoparticles, wherein the mesoporous material is at least one of mesoporous silica, mesoporous titanium dioxide, and mesoporous carbon; and A hyaluronic acid-modified layer covering the mesoporous material shell.
2. The drug carrier for suppurative arthritis according to claim 1, characterized in that, The liquid metal is pure gallium.
3. The drug carrier for suppurative arthritis according to claim 1, characterized in that, The liquid metal is a gallium-indium alloy, wherein the mass percentage of indium is 10%-25%.
4. The drug carrier for suppurative arthritis according to claim 1, characterized in that, The liquid metal is a ternary or multi-element alloy containing gallium, indium, and tin.
5. The drug carrier for suppurative arthritis according to claim 1, characterized in that, The liquid metal nanoparticles have a particle size of 50 nm - 200 nm.
6. The drug carrier for suppurative arthritis according to claim 1, characterized in that, The thickness of the mesoporous material shell is 10 nm - 30 nm, and the pore size is 2 nm - 5 nm.
7. The drug carrier for suppurative arthritis according to claim 1, characterized in that, The mesoporous material shell is a composite shell with an inner layer and an outer layer, wherein the inner layer is dense silica to ensure sealing, and the outer layer is mesoporous silica to achieve high drug loading.
8. The drug carrier for suppurative arthritis according to claim 1, characterized in that, The hyaluronic acid has a molecular weight of 5 kDa-500 kDa and a modification density of 5%-20% of the total mass of the drug carrier for septic arthritis.
9. A method for preparing a drug carrier for suppurative arthritis, characterized in that, Includes the following steps: Liquid metal, PVP and the first solvent were mixed, ultrasonicated, and centrifuged to disperse the precipitate in water to obtain LMP stock solution. LMP stock solution, second solvent, ammonia, and CTAB were mixed at 20℃-50℃, and TEOS was added dropwise. After the reaction, LMP@MSN was obtained. HA was dissolved in a third solvent, and EDC and NHS were added sequentially. The mixture was activated at room temperature. The activated HA solution was then added dropwise to the PBS dispersion of LMP@MSN. The mixture was stirred in the dark to obtain a drug carrier for septic arthritis.
10. The method according to claim 8, characterized in that, The method for preparing the drug carrier for suppurative arthritis specifically includes the following steps: Liquid metal and PVP were added to an alcohol-water mixture, and the mixture was ultrasonically treated in an ice-water bath. The precipitate was collected by centrifugation and dispersed in water to obtain LMP stock solution. LMP stock solution, ethanol, ammonia, and CTAB were mixed at 25℃-35℃, and TEOS was added dropwise. After the reaction, LMP@MSN was obtained. HA was dissolved in MES buffer, and EDC and NHS were added sequentially. The mixture was activated at room temperature. The activated HA solution was then added dropwise to the PBS dispersion of LMP@MSN and stirred in the dark to obtain a drug carrier for septic arthritis.