Targeted alveolar macrophage glycyrrhetinic acid liposome and preparation method thereof

Abstract

The invention discloses an alveolar macrophage glycyrrhetinic acid liposome and a preparation method thereof, and belongs to the field of biological medicines. The surface of glycyrrhetinic acid lipidosome is modified with alveolar macrophage targeting molecules, so that the lipidosome can specifically target M1 alveolar macrophages induced by lipopolysaccharide serving as a main component of the outer wall of gram-negative bacteria, entrapped glycyrrhetinic acid is ingested by the alveolar macrophages, M2 polarization is specifically induced, and the specific targeting effect is achieved. Lung inflammatory injury caused by gram-negative bacteria is reduced, lung tissue injury and fibrosis caused by excessive inflammation are prevented, and great significance is achieved for pneumonia caused by gram-negative bacteria.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, specifically to a glycyrrhetinic acid liposome targeting alveolar macrophages and its preparation method. Background Technology

[0002] Gram-negative bacterial pneumonia is a serious respiratory infection caused by Gram-negative bacteria, including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii, with high morbidity and mortality rates. Due to their complex cell wall structure and the presence of an outer membrane, Gram-negative bacteria are naturally resistant to many antibiotics. In recent years, with the widespread use of broad-spectrum antibiotics and inadequate hospital infection control measures, the incidence of drug-resistant Gram-negative bacterial infections has increased significantly, especially in the elderly, immunocompromised individuals, hospitalized patients, and patients with chronic diseases. Excessive inflammation caused by Gram-negative bacteria can lead to severe lung tissue damage, and even systemic inflammatory syndrome and multiple organ failure, making it a key issue in clinical severe infections.

[0003] However, due to the resistance of Gram-negative bacteria to multiple antibiotics, treatment options are severely limited. Appropriate antibiotics must be selected based on drug sensitivity testing results, and single-antibiotic therapy is often ineffective. In recent years, various methods to overcome bacterial resistance have been reported, including the search for novel antibiotic targets and other alternative antibiotic therapies (such as phage therapy, antimicrobial peptides, and immunotherapy). Immunotherapy, in particular, enhances the host's immune system, enabling it to more effectively recognize, engulf, and kill bacteria, improving pathogen clearance capabilities while reducing antibiotic usage and avoiding the resistance problems caused by over-reliance on antibiotics. Furthermore, immunotherapy can modulate the host's inflammatory response, preventing lung tissue damage and fibrosis caused by excessive inflammation, and also secrete repair factors to promote the repair and healing of damaged lung tissue. Alveolar macrophages, as a type of immune cell residing in the alveoli, play a multifaceted role in pneumonia immunotherapy; however, there are currently no drugs specifically targeting alveolar macrophages.

[0004] Traditional Chinese medicine (TCM) has a long history and wide application in the treatment of pneumonia. Unlike Western medicine's single-target approach, TCM can exert its anti-inflammatory effects through multiple targets and pathways, including regulating the body's immune function, anti-inflammation, broad-spectrum antibacterial activity, and antipyretic and expectorant effects. Licorice is one of the most commonly used herbs in many TCM prescriptions. Its main active ingredients include glycyrrhizic acid, glycyrrhetinic acid, glycyrrhizin, glycyrrhizin flavonoids, and glycyrrhizin. In recent years, its active ingredients have been reported to have anti-inflammatory, antiviral, antibacterial, immunomodulatory, and antitumor effects. CN 120037240 discloses the application of glycyrrhetinic acid or glycyrrhetinic acid liposomes in the preparation of drugs to protect against abdominal aortic aneurysms, revealing that glycyrrhetinic acid can effectively improve mortality after aortic rupture induced by Ang II treatment in mice, significantly improve the degradation of the aortic elastic fiber layer induced by Ang II treatment, and promote lipopolysaccharide (LPS)-induced macrophage polarization towards the M2 type. However, due to the poor water solubility of licorice, its complex composition making dosage control difficult, low bioavailability, and poor targeting, its onset of action is slow and its efficacy is not significant, hindering its further development in modern clinical applications. Therefore, developing an immunotherapy delivery system based on traditional Chinese medicine is of great significance for improving the bioavailability of traditional Chinese medicine, reducing toxic side effects, improving the efficacy against Gram-negative bacterial pneumonia, and reducing drug resistance. CN 102512369 A discloses a glycyrrhetinic acid solid lipid nanoparticle whose main components include the active ingredient glycyrrhetinic acid, pharmaceutically acceptable phospholipids, lipid materials, and surfactants. It can be used for various routes of administration, including oral and injectable administration, and is suitable for treating various diseases such as hepatitis, liver cancer, lung cancer, ovarian cancer, gastritis, gastric cancer, leukemia, and AIDS. However, this nanoparticle lacks targeted action for the corresponding diseases, which may lead to slow onset of action and long treatment cycles during the disease treatment process. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a glycyrrhetinic acid liposome targeting alveolar macrophages and its preparation method. By combining the glycyrrhetinic acid liposome with macrophage-targeting molecules, it specifically induces alveolar macrophage polarization, reduces the secretion of inflammatory cytokines, enhances the body's immunity, and exerts anti-inflammatory effects, thereby overcoming the disadvantages of Gram-negative bacterial resistance, low bioavailability of traditional Chinese medicine, and difficulty in controlling dosage.

[0006] The glycyrrhetinic acid liposomes targeting alveolar macrophages provided by the present invention include glycyrrhetinic acid liposomes containing β-glycyrrhetinic acid and phospholipids, and the surface of the glycyrrhetinic acid liposomes is modified with alveolar macrophage targeting molecules.

[0007] Furthermore, the purity of the β-glycyrrhetinic acid is 98%~100%.

[0008] Furthermore, the alveolar macrophage targeting molecule is one of the glycosylated polymers.

[0009] Furthermore, the alveolar macrophage targeting molecule is one of the monosaccharide-based amphiphilic polymers.

[0010] Furthermore, the alveolar macrophage targeting molecule is one of distearylphosphatidylethanolamine-polyethylene glycol-mannose, polylactic acid-glycolic acid copolymer-polyethylene glycol-galactose, distearylphosphatidylethanolamine-polyethylene glycol-glucose, and distearylphosphatidylethanolamine-polyethylene glycol-fucose.

[0011] Furthermore, the phospholipid is a type of soybean lecithin.

[0012] Furthermore, the soybean lecithin contains 40% phosphatidylcholine, 16% phosphatidylethanolamine, and 11% phosphatidylinositol.

[0013] Furthermore, the liposomes have a particle size of 100–200 nm.

[0014] This invention also provides a method for preparing the above-mentioned glycyrrhetinic acid liposomes targeting alveolar macrophages, specifically including the following steps: S1. Weigh phospholipids and glycyrrhetinic acid according to the proportion, dissolve them fully in an organic solvent, and then evaporate the organic solvent completely by rotary evaporation. By controlling the low-speed rotation, a uniform lipid film is formed on the surface of the round-bottom flask. S2. Add 0.154 M NaCl solution to the round-bottom flask in the above proportion and shake. Then, sonicate the suspension with a probe or in a water bath, and then dialyze it to obtain glycyrrhetinic acid liposomes by using a molecular weight cutoff of MWCO=3500 Da. S3. Weigh the alveolar macrophage targeting molecules according to the proportion, dissolve them in an appropriate amount of organic solvent, slowly add them to the liposomes, and then perform stirring, purification and membrane extrusion treatment in sequence to obtain alveolar macrophage targeting liposomes with uniform particle size loaded with glycyrrhetinic acid.

[0015] Furthermore, the organic solvent is one or a mixture of chloroform, methanol, ethanol, and diethyl ether.

[0016] The glycyrrhetinic acid liposomes targeting alveolar macrophages provided by this invention are used in the preparation of drugs for pneumonia caused by Gram-negative bacteria.

[0017] The beneficial effects of this invention are reflected in the following aspects: (1) This invention uses a variety of algorithms and network analysis methods to comprehensively screen all active ingredients of licorice that are related to anti-inflammatory effects. It utilizes big data and artificial intelligence to anchor key molecules, reduce the scope of experimental screening, and lower screening costs.

[0018] (2) This invention modifies alveolar macrophage targeting molecules on the surface of glycyrrhetinic acid liposomes, enabling the liposomes to specifically target M1 alveolar macrophages, thereby allowing the encapsulated glycyrrhetinic acid to be taken up by alveolar macrophages, specifically inducing M2 polarization, enhancing the anti-inflammatory function of alveolar macrophages, reducing lung inflammatory damage caused by Gram-negative bacteria, and preventing lung tissue damage and fibrosis caused by excessive inflammation by regulating the host's inflammatory response. This is of great significance for pneumonia caused by Gram-negative bacteria.

[0019] (3) The present invention constructs and prepares glycyrrhetinic acid liposomes with alveolar cell targeting by nanotechnology, which greatly improves the solubility of glycyrrhetinic acid, increases the encapsulation rate of glycyrrhetinic acid and enhances the bioavailability of glycyrrhetinic acid. Compared with traditional oral preparations, it increases the effective drug concentration at the local lesion site and further increases the bioavailability of glycyrrhetinic acid. Attached Figure Description

[0020] Figure 1 This study explores the associations between the active components of licorice (glycyrrhetinic acid, glycyrrhizin, and isoglycyrrhizin) and various anti-inflammatory diseases (such as pulmonary fibrosis, periodontitis, and neurodegenerative diseases) and their targets.

[0021] Figure 2 To detect lipopolysaccharide-induced alveolar macrophages after administration of glycyrrhetinic acid α and β by flow cytometry, (a) expression of the M1 surface marker CD80 and (b) expression of the M2 surface marker CD163 were obtained.

[0022] Figure 3 Transmission electron microscopy image of glycyrrhetinic acid liposomes; Figure 4 The hydrated particle size distribution and polydispersity index of glycyrrhetinic acid liposomes are shown. Figure 5 A standard curve for the determination of glycyrrhetinic acid by high performance liquid chromatography; Figure 6 To detect the drug loading capacity of glycyrrhetinic acid liposomes; Figure 7 For the detection of drug loading in non-targeted glycyrrhetinic acid liposomes; Figure 8 To determine cell viability values ​​when glycyrrhetinic acid liposomes were cytotoxic to MH-S and HUVEC cells using the MTT assay; Figure 9 Flow cytometry and confocal microscopy results show the specific uptake of glycyrrhetinic acid liposomes by mouse macrophages MH-S. Figure 10 To express surface markers of M1-M2 polarization induced by glycyrrhetinic acid liposomes in mouse alveolar macrophages; Figure 11The expression levels of mRNAs of inflammation- and repair-related cytokines induced by glycyrrhetinic acid liposomes in mouse alveolar macrophages were determined. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. The specific embodiments described herein are for illustrative purposes only and are not intended to limit the invention.

[0024] Example 1: Analysis of the correlation between licorice active ingredients, targets, and inflammatory diseases The study employed various algorithms and network analysis methods, including data integration and correlation analysis, literature mining, and bioinformatics tools to analyze the potential associations between compounds and targets, and between targets and diseases. According to the literature analysis, over 30 studies have shown that glycyrrhetinic acid, glycyrrhizin, and isoglycyrrhizin are associated with various anti-inflammatory diseases, suggesting that they may function by regulating inflammatory and fibrotic signaling pathways such as TGF-β, NF-κB, and Nrf2. Figure 1 The network analysis shown reflects the potential therapeutic effects of licorice active ingredients on inflammatory diseases by regulating multiple targets. For example, the high connectivity of targets PTGS2 and HSP90AA1 indicates that they are key regulatory factors, potentially closely related to various diseases (such as pulmonary fibrosis and neurodegenerative diseases). Furthermore, the ternary relationship between compounds, targets, and diseases reveals the regulatory network of common signaling pathways. By employing force-directed algorithms (such as Fruchterman-Reingold) to optimize node arrangement and combining data support from bioinformatics databases such as CTD, PubChem, DrugBank, and KEGG, this provides an important biological reference for exploring the potential mechanisms and key targets of licorice active ingredients in inflammation-related diseases.

[0025] Example 2: Flow cytometry detection of glycyrrhetinic acid-induced polarization of MH-S cells (mouse alveolar macrophages) Lipopolysaccharide (LPS) is a component of the outer wall of Gram-negative bacterial cell walls and can, to some extent, substitute for lipopolysaccharide in bacterial pneumonia caused by Gram-negative bacteria. Logarithmic growth phase MH-S cells were prepared into a density of 3 × 10⁻⁶ cells / mL using RPMI-1640 complete medium (containing 0.05 mM β-mercaptoethanol). 5Cell suspensions of 10 cells / mL were seeded into 12-well plates at a rate of 1 mL per well and cultured overnight at 37°C in a 5% CO2 incubator. The original culture medium was discarded, and RPMI-1640 medium containing 0.1 μg / mL lipopolysaccharide was added for induction for 24 h. The medium was then discarded, and MH-S cells were treated with RPMI-1640 medium containing 3 μg / mL α- and β-glycyrrhetinic acid for 24 h, respectively. RPMI-1640 medium without the drug and untreated MH-S cells served as controls. After incubation, cell surface markers were stained with FITC-labeled anti-mouse CD80 antibody and APC-labeled anti-mouse CD163 antibody, and the expression of each marker was detected by flow cytometry. Figure 2 Figure 'a' shows that both types of glycyrrhetinic acid can lead to decreased expression of CD80, a surface marker of M1 (pro-inflammatory) macrophages. Figure 2 Figure b shows increased expression of the surface marker CD163 in M2 (anti-inflammatory) macrophages. Results showed that both α- and β-glycyrrhetinic acid (GAA) could polarize LPS-induced M1 alveolar macrophages towards M2 macrophages, with β-GAA showing a better effect. Compared to α-GAA, the expression of the M2 surface marker CD163 was increased by 5.72%. Differences between β-GAA and α-GAA were marked with "*", indicating statistical significance.

[0026] Example 3: Preparation of glycyrrhetinic acid liposomes targeting alveolar macrophages 100 mg of soybean lecithin and 4 mg of β-glycyrrhetinic acid were weighed and dissolved thoroughly in ethanol. The organic solvent was evaporated to the bottom of the flask using a rotary evaporator to form a uniform lipid film. 10 mL of 0.154 M NaCl solution was added to the lipid film and the mixture was sonicated in a water bath for 5 minutes to obtain a liposome suspension. The obtained liposome suspension was purified by dialysis (MWCO=3500 Da) to remove free glycyrrhetinic acid before targeted modification. 50 mg of purified liposomes were taken, and distearate phosphatidylethanolamine-polyethylene glycol-glucose (molecular weight: 2000 Da) dissolved in ethanol was added dropwise while stirring. After stirring for 30 minutes, the organic solvent was removed by dialysis. The obtained liposomes were extruded through a membrane to obtain alveolar macrophage-targeting glycyrrhetinic acid liposomes with uniform particle distribution.

[0027] The prepared liposomes were characterized by dynamic light scattering and transmission electron microscopy for particle size, potential, and morphology. The results are as follows: Figure 3 and Figure 4As shown, ipo represents untargeted glycyrrhetinic acid liposomes, while lipoglu represents targeted glycyrrhetinic acid liposomes. The results indicate that the glycyrrhetinic acid liposomes linked to the target molecule have a particle size of approximately 150 nm, are spherical, have a larger diameter, and a polydispersity index (PDI) of less than 0.3, which is smaller than that of the untargeted glycyrrhetinic acid liposomes. Compared to the untargeted glycyrrhetinic acid liposomes, they exhibit a more uniform particle size distribution and better dispersibility.

[0028] In the existing technology CN120037240A, soybean lecithin and glycyrrhetinic acid (a mixture of α and β glycyrrhetinic acid) are taken at a mass ratio of 25:1 and fully dissolved in anhydrous ethanol. The anhydrous ethanol is completely evaporated by rotary evaporation to obtain a uniform lipid film. 100 mg of the lipid film is added to 10 mL of 0.154 M NaCl solution and shaken to form a suspension. The suspension is placed in a 30°C water bath and sonicated at 200 W for 15 minutes to hydrate, forming small liposomes. The obtained liposomes are purified by dialysis using a dialysis membrane or dialysis bag with a molecular weight cutoff of 3500 Da to obtain purified liposomes. The purified liposomes are then subjected to membrane extrusion to obtain glycyrrhetinic acid liposomes with a particle size of 100-150 nm.

[0029] The structure of glycyrrhetinic acid liposomes was detected by transmission electron microscopy (TEM). The encapsulation efficiency was determined by high-performance liquid chromatography (HPLC), and the particle size distribution was analyzed by dynamic light scattering (DLS). The glycyrrhetinic acid liposomes were found to be spherical particles with a uniform lipid bilayer structure, approximately 100 nm in size. The particle size distribution was uniform and normally distributed, with a hydrated particle diameter of 140.33 ± 1.81 nm. The glycyrrhetinic acid liposomes exhibited good polymerization and dispersion ability (PDI: 0.121 ± 0.011). The encapsulation efficiency was 30.05 ± 0.41%, and the Zeta potential was -38.42 ± 0.38 mV.

[0030] Example 4: Determination of glycyrrhetinic acid loading and encapsulation efficiency Take 400 μL of the glycyrrhetinic acid liposomes prepared in Example 3, mix with 400 μL of methanol, and vortex for 2 minutes to fully disrupt the liposomes. Centrifuge at 6500 rpm for 10 minutes, collect the supernatant, and perform HPLC analysis using a C-18 column (4.6 mm * 250 mm) with a mobile phase of methanol:water:glacial acetic acid = 79:20:1 and a flow rate of 0.8 mL / min. The results are as follows. Figure 5 As shown, a standard curve was plotted using glycyrrhetinic acid standard. Figure 5 The encapsulation efficiency of untargeted glycyrrhetinic acid liposomes was 55.23%. Figure 6 The encapsulation efficiency of glycyrrhetinic acid liposomes after targeted modification was 77.94%. Figure 7 Because the targeting molecule contains the hydrophobic-hydrophilic polymer fragment DSPE-PEG. 2000 This helps soybean lecithin and glycyrrhetinic acid drug molecules containing a hydrophobic backbone to form a more uniform drug-lipid film. During ultrasonic hydration, the film bends to form liposomes that encapsulate the drug. At the same time, the hydrophobic-hydrophilic polymer fragments can further stabilize the lipid structure, resulting in a higher encapsulation rate of the targeted modified glycyrrhetinic acid liposomes.

[0031] Therefore, β-glycyrrhetinic acid is more easily encapsulated by phospholipids than a mixture of α and β-glycyrrhetinic acid, and has better polymerizing and dispersing ability and better dispersibility.

[0032] Example 5: Cytotoxicity experiment of glycyrrhetinic acid liposomes Mouse alveolar macrophages (MH-S) and human umbilical vein endothelial cells (HUVECs) were seeded at 5000 cells / well in 96-well plates. After incubation at 37 °C with 5% CO2 for 24 h, cells were treated with different concentrations (128, 64, 32, 16, 8, 4, 2, 1, 0 μg / mL) of targeted-modified glycyrrhetinic acid liposomes. The control groups consisted of unmodified glycyrrhetinic acid liposomes and free glycyrrhetinic acid. After co-incubation with the drug for 24 h, 0.5 mg / mL of MTT was added to each well, and incubation continued for 4 h. The culture medium was then removed, and 150 μL of DMSO was added to each well. After shaking for 10 min, the absorbance at 570 nm was measured using a microplate reader. The data were analyzed, and the IC50 value was calculated. The results are as follows: Figure 8 As shown in the figure, targeted modification has no significant effect on liposome cytotoxicity, and its toxicity to HUVECs is less than that to MH-S. Example 6: Targeting ability of glycyrrhetinic acid liposomes. Following the method in Example 3, coumarin-6 fluorescent molecules were added during liposome preparation to enable intracellular tracking of the liposomes. Logarithmic growth phase mouse alveolar macrophages (MH-S) were collected and cultured in RPMI-1640 complete medium (containing 0.05 mM β-mercaptoethanol) at a ratio of 3 × 10⁻⁶ cells / year. 5 Cells were seeded per well in 12-well plates. After 24 h, targeted-modified liposomes were added and incubated with the cells for 1, 2, and 4 h, respectively. Unmodified liposomes served as the control group. Cells were harvested at each time point for flow cytometry and confocal imaging. The specific targeted uptake of liposomes by alveolar macrophages was assessed by the intensity of intracellular coumarin-6 fluorescence. Results are as follows: Figure 9 As shown in the figure, the targeted modification of liposomes significantly enhances the specific uptake of MH-S.

[0033] Example 7: Detection of surface markers and cytokines of glycyrrhetinic acid liposome-induced polarization in mouse alveolar macrophages MH-S cells in the logarithmic growth phase were collected and cultured in RPMI-1640 complete medium (containing 0.05 mM β-mercaptoethanol) to a density of 3 × 10⁻⁶ cells / year. 5 Cell suspensions of 10 cells / mL were seeded into 12-well plates at a rate of 1 mL per well and cultured overnight at 37°C in a 5% CO2 incubator. The original culture medium was discarded, and RPMI-1640 medium containing 0.1 μg / mL lipopolysaccharide was added for induction for 24 h. The culture medium was then discarded, and the cells were treated with targeted liposomes containing 3 μg / mL β-glycyrrhetinic acid for 24 h. Unmodified glycyrrhetinic acid liposomes, liposomes containing a mixture of α and β-glycyrrhetinic acid from CN120037240A, and uninduced MH-S cells were used as controls. After incubation, cell surface markers were stained with FITC-labeled anti-mouse CD80 antibody and APC-labeled anti-mouse CD163 antibody, and intracellular markers were stained with PE-labeled anti-mouse CD206 antibody. The expression of each marker was detected by flow cytometry. The results are shown below. Figure 10 As shown, the results indicated that glycyrrhetinic acid liposomes induced the expression of surface markers in mouse alveolar macrophages after M1-to-M2 polarization, with a decrease in the expression of M1 surface markers. Simultaneously, CD163 expression in MH-S cells treated with targeted liposomes was significantly increased compared to those treated with untargeted liposomes. Total RNA was extracted from cells, and the mRNA levels of secreted proteins and cytokines (iNOS, IL-6, IL-10) in mouse alveolar macrophages were detected using real-time quantitative PCR. The results are shown below. Figure 11 As shown, the results indicate that glycyrrhetinic acid liposomes can reduce the mRNA expression levels of inflammatory cytokines IL-6 and iNOS, and increase the mRNA expression level of inflammatory cytokine IL-10.

[0034] The β-glycyrrhetinic acid-targeting liposomes and unmodified β-glycyrrhetinic acid liposomes of this invention induce M1-to-M2 polarization in mouse alveolar macrophages. The reduction in M1-type surface marker expression is significantly less than that of the α- and β-glycyrrhetinic acid mixture liposomes in prior art CN120037240A, while the increase in M2-type surface marker expression is significantly greater. The β-glycyrrhetinic acid-targeting liposomes of this invention reduce lung inflammatory damage caused by Gram-negative bacteria by modulating the host's inflammatory response, preventing excessive inflammation-induced lung tissue damage and fibrosis, which is of great significance for pneumonia caused by Gram-negative bacteria.

Claims

1. A glycyrrhetinic acid liposome targeting alveolar macrophages, characterized in that, This includes glycyrrhetinic acid liposomes containing β-glycyrrhetinic acid and phospholipids, with the surface of the glycyrrhetinic acid liposomes modified with alveolar macrophage targeting molecules.

2. The glycyrrhetinic acid liposome targeting alveolar macrophages according to claim 1, characterized in that, The purity of the β-glycyrrhetinic acid is 98%~100%.

3. The glycyrrhetinic acid liposome targeting alveolar macrophages according to claim 1, characterized in that, The alveolar macrophage targeting molecule is one of the glycosylated polymers.

4. The glycyrrhetinic acid liposome targeting alveolar macrophages according to claim 1, characterized in that, The alveolar macrophage targeting molecule is one of the monosaccharide-based amphiphilic polymers.

5. The glycyrrhetinic acid liposome targeting alveolar macrophages according to claim 1, characterized in that, The alveolar macrophage targeting molecule is one of the following: distearylphosphatidylethanolamine-polyethylene glycol-mannose, polylactic acid-glycolic acid copolymer-polyethylene glycol-galactose, distearylphosphatidylethanolamine-polyethylene glycol-glucose, and distearylphosphatidylethanolamine-polyethylene glycol-fucose.

6. The glycyrrhetinic acid liposome targeting alveolar macrophages according to claim 1, characterized in that, The phospholipid is a type of soybean lecithin.

7. The glycyrrhetinic acid liposome targeting alveolar macrophages according to claim 1, characterized in that, The liposomes have a particle size of 100–200 nm.

8. A method for preparing glycyrrhetinic acid liposomes targeting alveolar macrophages, characterized in that, Specifically, the following steps are included: S1. Weigh phospholipids and β-glycyrrhetinic acid according to the proportion, dissolve them fully in an organic solvent, and then evaporate the organic solvent completely by rotary evaporation. By controlling the low-speed rotation, a uniform lipid film is formed on the surface of the round-bottom flask. S2. Add NaCl solution to the round-bottom flask in the above proportion and shake. Then, sonicate the suspension with a probe or in a water bath, and then dialyze it to obtain glycyrrhetinic acid liposomes by using a molecular weight cutoff of MWCO=3500 Da. S3. Weigh the alveolar macrophage targeting molecules according to the proportion, dissolve them in an appropriate amount of organic solvent, slowly add them to the liposomes, and then perform stirring, purification and membrane extrusion treatment in sequence to obtain alveolar macrophage targeting liposomes with uniform particle size loaded with glycyrrhetinic acid.

9. The glycyrrhetinic acid liposomes targeting alveolar macrophages prepared according to claims 1-8, characterized in that, It is used in the preparation of drugs for pneumonia caused by Gram-negative bacteria.

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