CN-122005853-A - Medicine carrier for suppurative arthritis and preparation method thereof

Abstract

The invention relates to the technical field of medicine carriers, in particular to a medicine carrier for suppurative arthritis and a preparation method thereof. The drug carrier comprises liquid metal nano particles, a mesoporous material shell layer coating the liquid metal nano particles and a hyaluronic acid modification layer coating the mesoporous material shell layer, wherein the liquid metal is gallium (Ga), gallium indium alloy (GaIn) or ternary or multi-element alloy containing gallium, indium and tin, and the mesoporous material is at least one of mesoporous silicon dioxide, mesoporous titanium dioxide and mesoporous carbon. The drug carrier can be used for loading different kinds of therapeutic agents (drugs) such as antibiotics (like clindamycin), anti-inflammatory drugs, antitumor drugs and the like, and the therapeutic agents can enter mesopores of a mesoporous material shell layer.

Inventors

• Xie Banglin
• ZHANG BIN
• YANG XIAOWEI
• Xiong Jiangyuan

Assignees

• 南昌大学第一附属医院

Dates

Publication Date

20260512

Application Date

20260323

Claims (10)

1. 1. A pharmaceutical carrier for suppurative arthritis, comprising: Liquid metal nano particles, wherein the liquid metal is gallium, gallium indium alloy or ternary or multi-element alloy containing gallium, indium and tin; A shell layer of mesoporous material coating the liquid metal nano particles, wherein the mesoporous material is at least one of mesoporous silicon dioxide, mesoporous titanium dioxide and mesoporous carbon, and And the hyaluronic acid modification layer is used for coating the mesoporous material shell layer.
2. 2. The drug carrier for suppurative arthritis according to claim 1, wherein the liquid metal is pure gallium.
3. 3. The drug carrier for suppurative arthritis according to claim 1, wherein the liquid metal is gallium-indium alloy, wherein the mass percentage of indium is 10% -25%.
4. 4. The pharmaceutical carrier for suppurative arthritis according to claim 1, wherein the liquid metal is a ternary or multicomponent alloy containing gallium, indium, tin.
5. 5. The drug carrier for suppurative arthritis according to claim 1, wherein the liquid metal nanoparticle has a particle size of 50 nm-200 nm.
6. 6. The drug carrier for suppurative arthritis according to claim 1, wherein the thickness of the mesoporous material shell layer is 10 nm-30 nm and the pore size is 2 nm-5 nm.
7. 7. The drug carrier for suppurative arthritis according to claim 1, wherein the mesoporous material shell layer is a composite shell having an inner layer and an outer layer, wherein the inner layer is dense silica to ensure sealability, and the outer layer is mesoporous silica to realize high drug loading.
8. 8. The drug carrier for suppurative arthritis according to claim 1, wherein the molecular weight of the hyaluronic acid is 5 kDa-500 kDa, and the modified density is 5% -20% of the total mass of the drug carrier for suppurative arthritis.
9. 9. A method for preparing a drug carrier for suppurative arthritis, which is characterized by comprising the following steps: mixing liquid metal, PVP and a first solvent, performing ultrasonic treatment, and dispersing the precipitate in water after centrifugation to obtain LMP stock solution; mixing LMP stock solution, a second solvent, ammonia water and CTAB at 20-50 ℃, dropwise adding TEOS, and reacting to obtain LMP@MSN; Dissolving HA in a third solvent, sequentially adding EDC and NHS, activating at room temperature, dripping the activated HA solution into PBS dispersion liquid of LMP@MSN, and stirring for reaction in a dark place to obtain the drug carrier for suppurative arthritis.
10. 10. The method according to claim 8, wherein the preparation method of the drug carrier for suppurative arthritis specifically comprises the following steps: adding liquid metal and PVP into an alcohol-water mixed solution, placing the mixed solution into an ice-water bath for ultrasonic treatment, centrifugally collecting sediment, and dispersing the sediment into water to obtain LMP stock solution; mixing LMP stock solution, ethanol, ammonia water and CTAB at 25-35 ℃, dropwise adding TEOS, and reacting to obtain LMP@MSN; dissolving HA in MES buffer solution, sequentially adding EDC and NHS, activating at room temperature, dripping the activated HA solution into PBS dispersion of LMP@MSN, and stirring for reaction in the absence of light to obtain the drug carrier for suppurative arthritis.

Description

Medicine carrier for suppurative arthritis and preparation method thereof Technical Field The invention relates to the technical field of medicine carriers, in particular to a medicine carrier for suppurative arthritis and a preparation method thereof. Background Suppurative Arthritis (SA) is an acute infectious disease common in orthopaedics, with high incidence and high disability rate in childhood populations. According to epidemiological studies, pediatric SA accounts for 21% of all bone joint infections, with staphylococcus aureus being the predominant pathogen, accounting for up to 85%. The lack of an intelligent response system aiming at SA pathological characteristics in the prior art is mainly caused by the existence of characteristic pathological microenvironment in the SA joint cavity, wherein the concentration of hyaluronidase (HAase) is 10-100 times of the normal level, the pH of joint fluid is reduced to 6.0-6.8 by lactic acid accumulation in an acidic pH environment, and the high expression of macrophage CD44 receptor and the increase of the expression level under inflammatory stimulus are 3-5 times. Meanwhile, the prior art lacks an efficient and safe antimicrobial metal ion delivery system. Gallium ions (Ga 3+) have a unique antibacterial mechanism, interfere with bacterial iron metabolism through an iron simulation strategy, are not easy to induce bacterial drug resistance, and have good biocompatibility (the FDA has approved gallium nitrate for clinical use). However, in the prior art, free Ga 3+ has a short half-life in vivo (less than 30 minutes), lacks a carrier system that would target Ga 3+ to the site of infection, and lacks an optimal regimen for co-administration of Ga 3+ with an antibiotic. Therefore, the prior art faces core technical problems of how to effectively penetrate macrophage membranes, kill intracellular latent bacteria to reduce SA recurrence rate, how to design a system with multiple antibacterial mechanisms, reduce drug-resistant bacteria generation and improve curative effects on drug-resistant bacteria such as MRSA, and how to construct a drug delivery system with high biocompatibility and low toxicity, and is suitable for long-term use of children patients. Disclosure of Invention The invention aims to provide a drug carrier for suppurative arthritis and a preparation method thereof, which aim to solve at least one technical problem in the prior art. The first aspect of the present invention provides a pharmaceutical carrier for suppurative arthritis, comprising: Liquid metal nanoparticles, wherein the liquid metal is gallium (Ga), gallium indium alloy (GaIn), or ternary or multi-element alloys containing gallium, indium, tin; A shell layer of mesoporous material coating the liquid metal nano particles, wherein the mesoporous material is at least one of mesoporous silicon dioxide, mesoporous titanium dioxide and mesoporous carbon, and And the hyaluronic acid modification layer is used for coating the mesoporous material shell layer. In the invention, the liquid metal nano-particles are inner cores, and the liquid metal nano-particles serve as physical support and delivery carriers of the whole system and serve as a reservoir of antibacterial ions Ga 3+. In the inflammatory acidic microenvironment of the joint cavity, the liquid metal nanoparticle core can undergo hydrolysis reaction, continuously and controllably release Ga 3+, and exert the unique 'iron competition' antibacterial effect. The outer surface of the liquid metal nanoparticle is completely coated by the intermediate layer (mesoporous material shell layer) to form a stable core-shell interface, so that aggregation and premature leakage of the liquid metal are prevented. The degradation kinetics of the core is directly regulated by the response of the outer layer structure to the microenvironment (e.g., pH decrease). The mesoporous material shell layer is coated outside the liquid metal nanoparticle core to form an inorganic shell layer with uniform nano pore channels (mesopores), and the function of the mesoporous material shell layer is that a large number of antibiotic molecules (such as clindamycin) are loaded by physical adsorption or capillary action by utilizing the high specific surface area and pore volume of the mesoporous material shell layer in a loading stage, and the pore channels are taken as a medicine diffusion channel in a release stage, and the surface of the mesoporous material shell layer can be taken as an anchoring site modified by outer hyaluronic acid. The mesoporous material shell layer is tightly attached to the liquid metal nanoparticle core through chemical bonds (such as Si-O-M, M is metal) and physical actions. The pore size and surface chemistry of the shell layer determine the loading and release rate of the antibiotic. The hyaluronic acid modification layer covers the outer surface of the Yu Jiekong material shell layer through chemical bonding (such as amide bond and