Drug-loaded liposome nano system, drug-loaded liposome particles, preparation method and application of drug-loaded liposome nano system and drug-loaded liposome particles in preparation of anti-inflammatory pain drugs

Abstract

The invention belongs to the technical field of biological nano-agents, and particularly relates to a drug-loaded liposome nano-system, particles, a preparation method and application of the drug-loaded liposome nano-system and the particles in preparation of drugs for resisting inflammatory pain. According to the nano system, lipidosome serves as a carrying tool, selenium-carbon quantum dots and raddeanin A are combined, the solubility and stability of the natural product raddeanin A can be effectively improved, and absorption and distribution of the natural product raddeanin A in vivo are enhanced. Meanwhile, the selenium-containing doped carbon quantum dots have catalytic activity similar to that of antioxidant enzymes, can catalytically decompose active oxygen substances, cannot be quickly depleted like natural products, and can continuously play an antioxidant role. The raddeanin A has remarkable anti-inflammatory activity and immunocompetence, the selenium-containing doped carbon quantum dots can simulate the activity of various enzymes and adjust the level of inflammatory reaction related substances, the raddeanin A and the selenium-containing doped carbon quantum dots are in synergistic interaction, efficient treatment of inflammatory pain is achieved, and the application prospect is good.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biological nanomedicine, and particularly relates to a drug-loaded liposome nanosystem, a particle, a preparation method and application thereof in preparation of an anti-inflammatory pain drug. BACKGROUND

[0002] Inflammatory pain is a common type of pain, which is caused by the inflammatory process triggered by tissue damage, infection, immune response, etc. When the body is stimulated or damaged by external factors, the local tissue releases a variety of inflammatory mediators, such as pro-inflammatory factors (interleukin-1β, interleukin-6, tumor necrosis factor-α, etc.), prostaglandins, histamine, etc., and is accompanied by accumulation of a large amount of reactive oxygen species (ROS) at the inflammatory site, which further leads to a vicious cycle of inflammatory mediators. These mediators can activate the receptors of nerve endings, leading to the transmission of pain signals, and at the same time cause inflammation reactions such as increased vascular permeability, plasma extravasation, leukocyte infiltration, etc., resulting in local symptoms such as redness, swelling, heat and pain.

[0003] Inflammatory pain not only brings physical pain to patients, but also has a serious impact on their quality of life and mental health. At present, the main method for dealing with inflammatory pain in clinical practice is still drug treatment. The main categories include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, opioid drugs, etc. However, for chronic inflammatory pain, long-term use of related drugs can cause serious side effects. For example, non-steroidal anti-inflammatory drugs can cause nausea, vomiting, ulceration of the gastrointestinal tract, and long-term use can also cause liver and kidney damage, and some patients may have allergic reactions such as skin rash and itching. Long-term use of glucocorticoid drugs can cause osteoporosis, femoral head necrosis, elevated blood sugar, elevated blood pressure, increased risk of infection, etc. Although opioid drugs have a significant analgesic effect, they are addictive and can cause drug dependence, and can also cause adverse reactions such as nausea, vomiting, constipation, respiratory depression, etc.

[0004] Natural molecules hold significant potential and numerous advantages in pain management. Their sources are widespread, including plants, animals, and microorganisms, and their diverse chemical structures provide abundant resources for drug development. Many natural molecules exhibit good biocompatibility and low toxicity, and are unlikely to induce drug resistance. However, while natural products hold significant potential in pain management, their application faces some limitations. Many natural products are hydrophobic, resulting in low solubility in aqueous environments, affecting drug absorption and bioavailability. This makes it difficult for drugs to reach target tissues or cells, reducing therapeutic efficacy. Traditional methods, such as using solubilizers or altering the route of administration, can improve solubility to some extent, but may introduce side effects or inconvenience issues. Furthermore, some natural products scavenge reactive oxygen species (ROS) through a depletion-type mechanism, limiting their ROS scavenging capacity. ROS play a crucial role in the pathogenesis of inflammatory pain, but natural products may be rapidly consumed at the site of inflammation due to high ROS concentrations or prolonged inflammation, failing to sustain their antioxidant and anti-inflammatory effects. This limits their efficacy in treating inflammatory pain.

[0005] Therefore, it is necessary to provide an anti-inflammatory pain medication that can effectively improve the bioavailability of natural drugs, enhance therapeutic effects, and prolong the duration of action. Summary of the Invention

[0006] To address the aforementioned problems, the present invention aims to provide a drug-loaded liposome nanosystem, particles, preparation method, and its application in the preparation of anti-inflammatory pain drugs. This drug-loaded liposome nanosystem combines efficient drug delivery, continuous scavenging of reactive oxygen species, elimination of inflammation, reduction of toxic side effects, and tolerance-free functions.

[0007] In a first aspect, the present invention provides a method for preparing a drug-loaded liposome nanosystem, the method comprising the following steps:

[0008] S1. A selenocysteine ​​solution with a pH of 8-10 is reacted at a temperature of 55-65℃. After the reaction is complete, the supernatant is obtained by centrifugation, yielding an aqueous solution containing selenium-doped carbon quantum dots (Se-CQDs).

[0009] S2. Lecithin, cholesterol, and polyethylene glycol are added to chloroform, followed by a methanol solution of cyperus rotundus extract A. The mixture is then evaporated under reduced pressure to form a lipid film. The resulting aqueous solution containing selenium-doped carbon quantum dots is then poured into the solution. The mixture is stirred at the phase transition temperature of polyethylene glycol to encapsulate the aqueous solution containing selenium-doped carbon quantum dots with the lipid film, thus obtaining the drug-loaded liposome nanosystem.

[0010] In some embodiments of the present invention, the polyethylene glycol is polyethylene glycol modified with distearate phosphatidylethanolamine and has a weight-average molecular weight of 2000.

[0011] In some embodiments of the present application, in step S2, the mass ratio of lecithin, cholesterol, polyethylene glycol and silafragrans A is (10-40):(5-25):(1-5):(0.5-20).

[0012] In some embodiments of the present application, in step S2, the total mass of lecithin, cholesterol, polyethylene glycol and silafragrans A to the feeding ratio of the aqueous solution of selenium-doped carbon quantum dots is (5-15) g:1 mL, and the content of selenium in the aqueous solution of selenium-doped carbon quantum dots is 0.05-0.3 mg / mL.

[0013] In some embodiments of the present application, the preparation method further comprises extruding the drug-loaded liposome nanosystem using a liposome extruder to make the particle size uniform.

[0014] In some embodiments of the present application, the pore size of the filter membrane of the liposome extruder is 80-150 nm.

[0015] In a second aspect of the present application, a drug-loaded liposome nanosystem is provided, which is prepared by the preparation method described above.

[0016] In a third aspect of the present application, a drug-loaded liposome nanoparticle is provided, which is obtained by freeze-drying the drug-loaded liposome nanosystem described above.

[0017] In a fourth aspect of the present application, the drug-loaded liposome nanosystem described above or the drug-loaded liposome nanoparticle described above is used in the preparation of an anti-inflammatory pain drug.

[0018] In some embodiments of the present application, the inflammatory pain is pain caused by tissue inflammation.

[0019] In a fifth aspect of the present application, an anti-inflammatory pain drug is provided, which comprises the drug-loaded liposome nanosystem described above or the drug-loaded liposome nanoparticle described above.

[0020] Compared with the prior art, the present application has the following beneficial effects:

[0021] (1) After being combined with Se-CQDs with enzyme activity and coated with liposomes, the technical effect of halofuginone A in treating inflammatory pain is significantly enhanced. The experimental results show that the liposome nanosystem not only greatly improves the dispersibility and stability of halofuginone A in the body, but also effectively overcomes the problems of low original bioavailability and poor targeting. The liposome coating further realizes the sustained release of halofuginone A and the directional enrichment of the inflammatory site and the central nervous system, significantly prolongs the effective action time of the drug in the lesion area. Ultimately, the composite system shows excellent effects of relieving inflammation and analgesia in a mouse model, providing an effective strategy for improving the clinical application of poorly soluble or low-efficiency natural drugs.

[0022] (2) The Se-CQDs in the drug-loaded liposome nanosystem provided by the application simulate the enzyme activities of superoxide dismutase, catalase and glutathione peroxidase, can continuously remove active oxygen at the inflammatory site, overcome the limitations of traditional natural products in depleting active oxygen, and provide more persistent and stable antioxidant support for the treatment of inflammatory pain, effectively relieving inflammation.

[0023] (3) The liposome nanosystem combined with natural molecules halofuginone A and Se-CQDs not only enhances the anti-inflammatory and analgesic effect, but also reduces the dose of single component, and reduces the potential toxic side effects. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 The transmission electron microscopy images and the hydrated particle size distribution graphs of Se-CQDs and the drug-loaded liposome nanosystem synthesized in Example 3 are shown in the following figure:

[0025] Figure 2 The enzyme activity detection results of Se-CQDs in Test Example 1 are shown in the following figure. The left graph is the absorbance at a wavelength of 340 nm over time curve when detecting the glutathione peroxidase activity of Se-CQDs. The right graph is the ultraviolet-visible spectrum graph of the superoxide dismutase activity detection;

[0026] Figure 3 The cytotoxicity results of the drug-loaded liposome nanoparticles synthesized in Example 3 on BV2 cells and primary microglial cells are shown in the following figure:

[0027] Figure 4 The real-time fluorescence quantitative PCR experiment results of the drug-loaded liposome nanoparticles synthesized in Example 3 in eliminating LPS-induced inflammation of primary microglial cells are shown in the following figure:

[0028] Figure 5 The fluorescence microscope images of the drug-loaded liposome nanosystem synthesized in Example 3 in eliminating the t-butyl hydroperoxide-induced BV2 cell oxidative stress model are shown in the following figure:

[0029] Figure 6 Figure 1 shows the treatment effect of the granules prepared in Examples 1-3 and Comparative Examples 1-2 on a mouse inflammatory pain model. Specific embodiments

[0030] The above content of the present application is further described in detail by the following specific examples, but does not represent the limitation of the present application by the examples.

[0031] The reagents, materials and instruments used in the following examples are as follows:

[0032] Reagents: selenocystine, lecithin, sodium hydroxide, cholesterol, polyethylene glycol, rhizanthopsin A, chloroform, methanol, cell culture medium, 2',7'-dichlorofluorescein diacetate, cell nucleus staining solution;

[0033] Materials: dialysis bag, glutathione peroxidase detection kit, superoxide dismutase activity detection kit, cell proliferation and toxicity kit;

[0034] Instruments: oil bath pot, high-speed centrifuge, inductively coupled plasma emission spectrometer, rotary evaporator, cell wall breaking machine, ultrasonic cleaner, liposome extruder, confocal microscope, transmission electron microscope, Malvern dynamic light scattering instrument.

[0035] Example 1

[0036] (1) Dissolve selenocystine in distilled water to prepare a 20 mg / mL solution. Add 0.5 mol / L sodium hydroxide solution dropwise, and adjust the pH of the mixed solution to 9. Pass nitrogen gas for 15 minutes to remove some air in the solution. Stir at room temperature for 1 hour, then transfer to an oil bath pot, and stir at 60°C for 24 hours. After the solution cools down, centrifuge at 12,000 rpm for 15 minutes. Collect the supernatant and dialyze the solution in a 500 Da dialysis bag. First, boil the 500 Da dialysis bag in boiling water for 10 minutes, then add the centrifuged supernatant to the dialysis bag, and dialyze in water for 48 hours, changing the water three times at 2, 6, and 24 hours, respectively, to obtain a water solution of selenium-doped carbon quantum dots. After freeze-drying, Se-CQDs granules are obtained.

[0037] (2) Mix 1 mL of lecithin chloroform solution (concentration of 5.5 mg / mL), 1 mL of cholesterol chloroform solution (concentration of 1.6 mg / mL), 1 mL of polyethylene glycol chloroform solution (concentration of 0.8 mg / mL), and 0.1 mL of rhizanthopsin A methanol solution (concentration of 10 mg / mL), and evaporate and filter under reduced pressure to form a lipid film.

[0038] (3) Take the selenium-doped carbon quantum dots prepared in step (1) dissolved in water, and prepare a solution with a Se element concentration of 0.2 mg / ml. Take 1 mL of the solution and add it to the lipid film obtained in step (2). Ultrasonic water bath at 37 degrees Celsius for 20 seconds at a power of 800 watts, then stir at 50 degrees Celsius for 5 minutes at a stirring temperature of 37 degrees Celsius and a stirring speed of 600 revolutions per minute, then ultrasonic dispersion for 30 seconds in a cell disruptor to form liposomes, and obtain a liposome dispersion. The working conditions of the cell disruptor are as follows: the ultrasonic probe has a diameter of 3 mm, the working power is 800 watts, and the working mode is intermittent mode with 5 seconds of work and 5 seconds of stop.

[0039] (4) The liposome dispersion obtained in step (3) is extruded through a liposome extruder and then dialyzed to obtain a drug-loaded liposome nanosystem containing liposomes with uniform particle size. The filter membrane used in the liposome extruder has a pore size of 100 nanometers, and the extrusion is performed twice. After freeze-drying, drug-loaded liposome nanoparticles are obtained.

[0040] The dialysis method is as follows: first, boil a 3500 dalton dialysis bag for 10 minutes, then add the liposome solution extruded by the liposome extruder to the dialysis bag, and dialyze in clean water for 48 hours, changing the water three times at the 2nd, 6th, and 24th hours.

[0041] The freeze-drying method is as follows: freeze the solution in liquid nitrogen for 1-3 minutes, then place it in a freeze dryer, set the freeze dryer to -50 degrees and the pressure to 20 Pa, and freeze-dry for 24 hours.

[0042] Example 2

[0043] The concentration of the methanol solution of ferulic acid in step (2) in Example 1 is modified to 15 mg / mL.

[0044] The other conditions remain unchanged.

[0045] Example 3

[0046] The concentration of the methanol solution of ferulic acid in step (2) in Example 1 is modified to 20 mg / mL.

[0047] The other conditions remain unchanged.

[0048] Comparative Example 1 (Se-CQDs alone)

[0049] Prepare Se-CQDs particles according to step (1) in Example 1.

[0050] Comparative Example 2 (ferulic acid alone)

[0051] Commercially available ferulic acid

[0052] The Se-CQDs and the drug-loaded liposome nanosystem synthesized in Example 3 were subjected to relevant characterization, and the characterization methods were as follows:

[0053] Test Example 1: Transmission electron microscopy and hydration particle size of Se-CQDs and the drug-loaded liposome nanosystem synthesized in Example 3

[0054] The Se-CQDs were dispersed in water and ultrasonically treated for 30 minutes to make them uniformly dispersed. An appropriate amount of the dispersion was dropped on a copper grid and naturally dried at room temperature for standby. The Se-CQDs-loaded liposome nanoparticles were subjected to negative staining with uranyl acetate for standby. TALOS transmission electron microscopy was used for characterization. The acceleration voltage was set to 200 kilovolts. The experimental results showed that the Se-CQDs were regular spherical, uniformly dispersed, and had a particle size of about 5.8 nanometers, without obvious agglomeration, indicating that the Se-CQDs had good monodispersity. The Se-CQDs were dispersed in deionized water to prepare solutions of different concentrations. Malvern dynamic light scattering was used to measure the hydration particle size. The temperature was set to 25 degrees Celsius, the detection angle was 90 degrees, each sample was measured 3 times, and the average value was taken. The Se-CQDs showed good stability at different concentrations, with an average hydration particle size of 8.5 nanometers and a narrow particle size distribution, indicating that the Se-CQDs had good solubility and stability in aqueous solution and could maintain their nanoscale particle size under physiological conditions. After the same treatment, the transmission electron microscopy of the liposome nanosystem loaded with Se-CQDs and rhizoxin A showed uniform particle size. The hydration particle size test results showed that the particle size was 160 nanometers, also with good stability, and could maintain its nanoscale particle size under physiological conditions, which was beneficial to its application in biological systems.

[0055] Test Example 2: Detection of glutathione peroxidase activity and superoxide dismutase activity of Se-CQDs solution

[0056] (1) Glutathione peroxidase activity test: a mixed system of glutathione, reduced nicotinamide adenine dinucleotide phosphate, glutathione reductase, and hydrogen peroxide was prepared, and different concentrations of Se-CQDs were added, and the reaction was carried out at 37 degrees Celsius. The total reaction volume was 500 microliters. In the reaction, the concentration of glutathione was 2 mM, the concentration of reduced nicotinamide adenine dinucleotide phosphate was 0.4 mM, the activity of glutathione reductase was 0.85 U / mL, and the concentration of hydrogen peroxide was 240 uM. The change in absorbance at 340 nm was detected by ultraviolet-visible spectrophotometer in dynamic mode. The results showed that the Se-CQDs solution exhibited good glutathione peroxidase activity.

[0057] (2) Superoxide dismutase activity detection: methionine and riboflavin, nitrogen blue tetrazolium and different concentrations of Se-CQDs solution were mixed, after light irradiation for 30 minutes, the absorbance value at 560 nm was measured, the results showed that Se-CQDs showed good superoxide anion scavenging capacity. In the reaction, the concentration of methionine was 10 mM, the concentration of riboflavin was 20 uM, and the concentration of nitrogen blue tetrazolium was 0.1 uM.

[0058] Test Example 3: Cytotoxicity experiment of the drug-loaded liposome nanosystem prepared in Example 3

[0059] Cell Counting Kit-8 cell proliferation and toxicity kit was used for cytotoxicity determination. BV2 cells were grown in 96-well plates with a seeding density of 10^4 cells / well. Exponentially growing cells and Example 3 were incubated for 24 hours, then incubated with CCK8 kit for 2 hours, and OD was measured at 450 nm to prove cell viability. Cell viability (%) = [OD (treatment group) - OD (blank group)] / [OD (control group) - OD (blank group)] x 100%. The results showed that the drug-loaded liposome nanoparticles SLR prepared in Example 3 had good biological safety.

[0060] Test Example 4: Real-time fluorescence quantitative PCR experiment to test the influence of the drug-loaded liposome nanosystem prepared in Example 3 on the expression amount of inflammatory factors in the LPS-induced microglial cell inflammation model

[0061] The BV2 cells were seeded in a six-well plate, and after the cells adhered, lipopolysaccharide (100 ng / mL) and drug-loaded liposome nanosystem (80 ug / mL) were added. After 24 hours of incubation, the RNA in the cells was extracted. The total RNA was reversely transcribed into cDNA using oligonucleotide primers. In addition, qPCR analysis was performed using SYBR Green I Dye Detection on a real-time detection system (Rotor-Gene 6000, QIAGEN, Hilden, Germany). The TNF-a, IL-1b, and GAPDH primer sequences were as follows: TNF-a forward, 5'-GTT CTA TGG CCC AGA CCC TCA C-3', and reverse, 5'-GGC ACC ACT AGT TGG TTG TCT TTG-3'; IL-1b forward, 5'-TCC AGG ATG AGG ACA TGA GCA C-3', and reverse, 5'-GAA CGT CAC ACA CCA GCA GGT TA -3'; GAPDH forward, 5'-AAA TGG TGA AGG TCG GTG TGA AC-3', and reverse, 5'-CAA CAA TCT CCA CTT TGC CAC TG-3'. PCR amplification was performed at 95 degrees Celsius for 30 seconds, followed by 40 cycles of 95 degrees Celsius for 5 seconds and 60 degrees Celsius for 45 seconds. GAPDH was used as an endogenous control to normalize the difference in mRNA. Quantification was performed using the GAPDH Ct (mRNA) normalized cycle threshold, and the 2−ΔΔCT method was used for analysis. The experimental results showed that the drug-loaded liposome nanomedicine prepared in Example 3 had the ability to reduce pro-inflammatory factors.

[0062] Test Example 5: Cell fluorescence imaging experiment to test the effect of the drug-loaded liposome nanosystem prepared in Example 3 on the content of reactive oxygen species in the t-butyl hydroperoxide-induced microglial cell oxidative stress model

[0063] The BV2 cells were seeded in a confocal culture dish, and after the cells adhered, the drug-loaded liposome nanosystem was co-incubated with the cells for 4 hours. Then, 40 micromoles per liter of t-butyl hydroperoxide was added to the model group and the liposome nanoparticle group for 1 hour to induce oxidative stress. At the same time, a blank control group was set. Finally, 10 micromoles per liter of 2',7'-dichlorodihydrofluorescein diacetate probe was used to stain for 30 minutes, and the fluorescence intensity of the probe was observed using a confocal microscope. The results showed that the drug-loaded liposome nanosystem could significantly reduce the level of reactive oxygen species in the t-butyl hydroperoxide-induced microglial cell oxidative stress model.

[0064] Test Example 6: Mouse behavior experiment

[0065] Adult male ICR mice with a body weight of 20 ~ 28 grams were raised in a humidity-controlled environment (26°C, 12-hour light-dark cycle) and freely fed. All animal experimental procedures were approved by the declaration of the Nantong University Experimental Animal Center. After the mice were anesthetized with isoflurane, 20 microliters of complete Freund's adjuvant was injected into the left hind paw to induce inflammatory pain and establish a mouse inflammatory pain model. After 3 days of complete Freund's adjuvant injection, different formulations were injected and mouse behavior tests were performed. Von Frey test was performed on mice, and before baseline testing, the animals were placed in a box on a metal mesh floor for at least 2 days, and given 30 minutes of adaptation time before testing. Next, the left hind paw was stimulated with a series of von Frey hair with logarithmic increasing hardness (0.02-2.56 g) to determine the 50% paw withdrawal threshold of the mice. The experimental results show that the application has long-acting treatment ability and good treatment effect on inflammatory pain compared with the comparative examples (1-2), and the effect of example 3 is the best.

[0066] The application provides a drug-loaded liposome nanosystem, a particle, a preparation method and an application idea of the drug-loaded liposome nanosystem in preparation of an anti-inflammatory pain medicine. The drug-loaded liposome nanosystem combines the functions of the enzyme activity of Se-CQDs, the liposome and the mimetic enzyme activity of rhizoma zedoariae element A, the regulation of inflammatory factors and long-acting delivery, realizes an inflammatory pain treatment scheme with the functions of efficient drug delivery, synergistic and continuous scavenging of active oxygen and reduction of toxic side effects, has good biocompatibility and clinical application prospect, and is expected to provide a new effective method for chronic inflammatory pain treatment. There are many methods and approaches to specifically realize the technical scheme, and the above description is only a preferred embodiment of the application, and it should be pointed out that, for ordinary skilled persons in the technical field, some improvements and refinements can be made without departing from the principle of the application, and these improvements and refinements should also be regarded as the protection scope of the application. The components not explicitly described in the embodiment can be realized by using the prior art.

Claims

1. A method for preparing a drug-loaded liposome nanosystem, characterized in that, The preparation method comprises the following steps: S1. A selenocystine solution with a pH value of 8-10 is reacted at a temperature of 55-65℃, and after the reaction is completed, the supernatant is obtained by centrifugation to obtain a water solution containing selenium-doped carbon quantum dots; S2. Egg phospholipid, cholesterol and polyethylene glycol are added to chloroform, and then a methanol solution of rhizoxin A is added, and the volatile is extracted by vacuum filtration, and after the formation of a lipid membrane, the water solution containing selenium-doped carbon quantum dots is poured into the water solution containing selenium-doped carbon quantum dots, and the lipid membrane is wrapped around the water solution containing selenium-doped carbon quantum dots by stirring at the phase transition temperature of the polyethylene glycol to obtain the drug-loaded liposome nanosystem.

2. The production method according to claim 1, characterized by, In step S2, the mass ratio of egg phospholipid, cholesterol, polyethylene glycol and rhizoxin A is (10-40):(5-25):(1-5):(0.5-20).

3. The production method according to claim 2, characterized by, In step S2, the total mass of egg phospholipid, cholesterol, polyethylene glycol and rhizoxin A to the feeding ratio of the water solution containing selenium-doped carbon quantum dots is (5-15) g:1 mL, and the content of selenium in the water solution containing selenium-doped carbon quantum dots is 0.05-0.3 milligrams per milliliter.

4. The production method according to claim 1, characterized by, The preparation method further comprises extruding the drug-loaded liposome nanosystem using a liposome extruder to make the particle size uniform.

5. The preparation method according to claim 4, characterized in that, The pore size of the filter membrane of the liposome extruder is 80-150 nanometers.

6. A drug-loaded liposome nanosystem, characterized in that, The drug-loaded liposome nanosystem is prepared by the preparation method according to any one of claims 1-5.

7. Drug-loaded liposome nanoparticles, characterized in that, The drug-loaded liposome nanoparticle is obtained by freeze-drying the drug-loaded liposome nanosystem according to claim 6.

8. The use of the drug-loaded liposome nanosystem according to claim 7 or the drug-loaded liposome nanoparticle according to claim 8 in the preparation of an anti-inflammatory pain medicine.

9. Use according to claim 8, characterized in that, The inflammatory pain is pain caused by tissue inflammation.

10. An anti-inflammatory analgesic medicament, characterized by, The anti-inflammatory pain medicine comprises the drug-loaded liposome nanosystem according to claim 7 or the drug-loaded liposome nanoparticle according to claim 8. The inflammatory pain is pain caused by tissue inflammation. The anti-inflammatory pain medicine comprises the drug-loaded liposome nanosystem according to claim 7 or the drug-loaded liposome nanoparticle according to claim 8.

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