Multifunctional honokiol nanoparticles as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of nano-drugs, and particularly relates to multifunctional honokiol nano-particles and a preparation method and application thereof.The honokiol nano-particles are prepared by using rhamnolipid modified chitosan as a carrier and loading honokiol; according to the nano-particles, an amido bond formed between rhamnolipid and chitosan can be subjected to targeted decomposition under the acidic condition of a bacterial infection part, and the released rhamnolipid can destroy a bacterial biofilm; further, permeation of the natural antibacterial agent honokiol and chitosan at the infected part is enhanced, and synergistic sterilization is realized; meanwhile, the planktonic bacteria re-adhesion resistance characteristic of rhamnolipid can inhibit the re-formation of a biofilm, the full-stage sterilization of'destroying the biofilm, killing bacteria in the film and inhibiting the re-adhesion of residual bacteria 'of the nanoparticles is finally realized, and the multifunctional honokiol nano platform is suitable for preventing and treating infectious diseases such as wound infection and bacterial peritonitis.

Description

Technical Field

[0001] This invention belongs to the field of nanomedicine technology, specifically relating to a multifunctional honokiol nanoparticle, its preparation method, and its application. Background Technology

[0002] Bacterial infections can lead to various diseases and complications, seriously threatening global public health security. The overuse and abuse of antibiotics have resulted in the continuous emergence of drug-resistant strains. Among them, methicillin-resistant Staphylococcus aureus (MRSA) exhibits multidrug resistance and high pathogenicity, and is a major pathogen causing skin infections, pneumonia, sepsis, and hospital-acquired infections. More seriously, MRSA readily forms biofilms, which not only restricts antibiotic penetration, allowing bacteria to evade the host and immune response, but also leads to recurrent infections and difficulty in treatment due to the continuous release of airborne bacteria. Clinically, vancomycin and other drugs are commonly used for treatment; however, with the increased use of antibiotics, the risk of drug resistance has increased dramatically. Furthermore, the development of new antibiotics lags far behind the development of bacterial resistance, making the prevention and treatment of MRSA in clinical practice extremely challenging. Therefore, there is an urgent need to develop new treatment strategies to effectively eradicate MRSA and its biofilms.

[0003] Plant-derived natural antibacterial drugs have received widespread attention in recent years due to their diverse antibacterial mechanisms and low risk of drug resistance. Furthermore, many natural antibacterial agents also possess anti-inflammatory and antioxidant pharmacological effects, further enhancing their effectiveness in treating bacterial infections. Honokiol (HNK), a bisphenol compound extracted from the traditional Chinese medicine Magnolia officinalis, exhibits significant anti-MRSA activity. However, HNK's low water solubility, poor stability, and low bioavailability hinder its clinical development and application.

[0004] Multifunctional nanoparticle drug delivery systems can address issues such as low drug solubility, poor stability, and low bioavailability. Furthermore, targeted drug delivery can be achieved through structural design, representing a promising new strategy for antibacterial drug development. In particular, bacterial microenvironment-responsive nanoparticles (pH-responsive, redox-responsive, and enzyme-responsive, etc.) are considered a new trend in antibacterial nanoparticle formulation development, enabling targeted drug delivery to the infection site. However, chemically synthesized antibacterial materials suffer from stringent synthesis conditions and poor biocompatibility. Natural antibacterial nanomaterials have received widespread attention in recent years due to their excellent biocompatibility and safety. Among them, chitosan (COS), a natural cationic polysaccharide, exhibits good biocompatibility and excellent antibacterial and anti-inflammatory properties, and has been widely used in drug delivery systems. Rhamnolipid (RHL), an anionic biosurfactant, possesses excellent anti-biofilm activity. It can disrupt MRSA biofilms by damaging extracellular polymers and inhibiting the re-adhesion of planktonic bacteria, thereby increasing antibacterial drug penetration.

[0005] In summary, given the challenges in treating MRSA and its biofilm-borne infections in clinical practice, and in order to overcome the problems of poor solubility, low bioavailability, and difficulty in drug development of traditional Chinese medicine monomers and magnolol, it is urgent to develop new antibacterial agents with good biocompatibility, high safety, and low risk of inducing drug resistance. Summary of the Invention

[0006] This invention proposes a multifunctional honokiol nanoparticle, its preparation method, and its application. The formulation uses rhamnolipid-modified chitosan as a carrier, loading a small molecule natural antibacterial drug and honokiol (HNK@RHL-COS). This drug-loaded system can decompose in the low pH environment of the bacterial infection site, releasing rhamnolipids to disrupt the biofilm, thereby increasing the penetration of the natural antibacterial agent, honokiol, and chitosan at the infection site, achieving synergistic bactericidal action against MRSA. Simultaneously, rhamnolipids can inhibit the adhesion of residual bacteria, ultimately achieving a comprehensive bactericidal process integrating "biofilm disruption - killing bacteria within the biofilm - inhibiting re-adhesion of residual bacteria."

[0007] The technical solution provided by this invention is as follows:

[0008] The first objective of this invention is to provide a multifunctional honokiol nanoparticle, wherein the honokiol nanoparticle is prepared by loading honokiol onto chitosan modified with rhamnolipid as a carrier.

[0009] A second objective of this invention is to provide a method for preparing the aforementioned magnolol nanoparticles, comprising the following steps:

[0010] (1) Add sodium polyphosphate and rhamnolipin solution dropwise to chitosan solution and stir;

[0011] (2) Add glutaraldehyde solution dropwise to the mixed solution obtained in step (1) and stir to crosslink; dialyze the resulting solution in PBS at pH 7.4 to obtain rhamnolipin-chitosan solution;

[0012] (3) Add the honokiol solution dropwise to the rhamnolipin-chitosan solution obtained in step (2), stir, and sonicate with a probe; and dialyze in PBS at pH 7.4 to remove unencapsulated drug, thus obtaining honokiol nanoparticles.

[0013] Preferably, the volume ratio of chitosan, rhamnolipid, and sodium polyphosphate in step (1) is 1:(0.17-1):(0.1-0.5), and the dropping rate is 1 drop / s.

[0014] Preferably, the volume ratio of the glutaraldehyde solution in step (2) to the mixed solution obtained in step (1) is 1:(50-100), and the dropping rate is 1 drop / s.

[0015] Preferably, in step (3), the volume ratio of magnolol solution to rhamnolipin-chitosan solution is 1:(2-15); the ultrasonic power is 10-50kHz and the ultrasonic time is 1-5min.

[0016] A third objective of this invention is to provide the application of the described magnolol nanoparticles or the magnolol nanoparticles prepared by the described preparation method in the preparation of antibacterial drugs.

[0017] A fourth objective of this invention is to provide the application of the described magnolol nanoparticles or the magnolol nanoparticles prepared by the described preparation method in the preparation of drugs for treating inflammatory / infectious diseases.

[0018] Preferably, the inflammatory / infectious disease includes one or more of wound infection, bacterial pneumonia, and peritonitis.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] (1) High biofilm penetration and efficient sterilization throughout the entire process: This invention discloses for the first time a multifunctional honokiol nanoparticle, which uses rhamnolipid-modified chitosan as a carrier to load natural antibacterial small molecules and honokiol to prepare nanoparticles (HNK@RHL-COS). The nanoparticles first undergo targeted decomposition at the site of bacterial infection under acidic conditions (pH 5.5). Then, the released rhamnolipids destroy the biofilm by dispersing extracellular polysaccharides and proteins, thereby enhancing the penetration of natural antibacterial agents, honokiol and chitosan at the site of infection, achieving synergistic sterilization. The anti-plankton re-adhesion properties of rhamnolipids inhibit biofilm reformation, ultimately achieving sterilization throughout the entire process.

[0021] (2) pH-responsive targeted sterilization: The amide bonds formed by the carboxyl groups of rhamnolipin and the amino groups of chitosan in the nanoparticles of this invention can be broken under acidic conditions at the site of infection, thereby achieving pH-responsive targeted drug release.

[0022] (3) Good biocompatibility and low risk of drug resistance: The nanoparticles of this invention are prepared from chitosan, rhamnolipid, and magnolol, all of which are natural small molecules with diverse antibacterial mechanisms, greatly improving the safety of the formulation and making them less likely to induce drug resistance compared to traditional antibiotics. The nanoparticles have rich pharmacological effects, not only possessing antibacterial functions but also anti-inflammatory functions, providing a novel strategy for the prevention and treatment of infectious diseases caused by bacteria. Attached Figure Description

[0023] Figure 1 This is a schematic diagram illustrating the preparation process and mechanism of action of the present invention;

[0024] Figure 2 The above are the characterization results of multifunctional and magnolol nanoparticles in the embodiments of the present invention;

[0025] Note: (A) TEM results of RHL-COS nanoparticles; (B) TEM results of HNK@RHL-COS nanoparticles; (C) Nanoparticle size determination results; (D) Nanoparticle potential determination results; (EG) Stability test results of nanoparticles at 4℃, room temperature and 50% FBS; (H) FT-IR determination results; (I) Raman spectroscopy determination results; (J) In vitro release results;

[0026] Figure 3 The results of the in vitro antibacterial activity and biofilm formation of multifunctional and magnolol nanoparticles in the embodiments of the invention;

[0027] Note: (A, B) OD values ​​of different concentrations of HNK@RHL-COS, RHL-COS, and HNK co-incubated with MRSA for 12 h. 600 Values ​​and plate count images; (C, D) OD values ​​measured every 2 hours after co-incubation of different concentrations of HNK@RHL-COS with MRSA. 600 Values ​​and plate count images; (E) Effects of HNK@RHL-COS, RHL-COS and HNK on MRSA biofilm formation; (F) Effects of HNK@RHL-COS, RHL-COS and HNK on mature MRSA biofilm. Figure 4 The results of safety tests on multifunctional and magnolol nanoparticles in the embodiments of the invention are shown.

[0028] Note: (A, B) Results of nanoparticle hemolysis assay; (C, D) Results of nanoparticle cytotoxicity assay; (E) Results of H&E staining of mouse heart, liver, spleen, lung, and kidney in vivo safety assay for nanoparticles.

[0029] Figure 5 The invention provides an example of the therapeutic effect of multifunctional and magnolol nanoparticles on a mouse wound model infected with MRSA.

[0030] Note: (A) Schematic diagram of the MRSA-infected mouse wound model experiment; (B, C) Changes in the wound area of ​​mice during treatment; (D, E) Results of wound bacterial load measurement during treatment; (F) Results of bacterial count in wound skin tissue after treatment; (G) Results of Masson and H&E staining of wound skin tissue after treatment; (HK) Serum levels of inflammatory factors IL-1β, IL-6, TNF-α and NO after treatment;

[0031] Figure 6 This invention demonstrates the therapeutic effect of multifunctional and magnolol nanoparticles on a mouse model of MRSA-infected bacterial peritonitis.

[0032] Note: (A) Schematic diagram of the experimental process of MRSA-infected mouse bacterial peritonitis model; (BD) Results of bacterial load measurement in ascites fluid, extracellular bacteria and intracellular bacteria in each group of mice; (E) H&E staining results of heart, liver, spleen, lung and kidney in each group of mice (green represents: cell necrosis; yellow represents: erythroid cell increase; blue represents: granulocyte increase; black represents: fibroblast proliferation; dark green represents: alveolar epithelial cell proliferation; purple represents: cell degeneration); (FI) Serum levels of inflammatory factors NO, IL-1β, IL-6 and TNF-α after treatment; Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described clearly and completely below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art, and the materials, reagents, etc., used in the following embodiments are commercially available unless otherwise specified.

[0034] In the following examples, sodium polyphosphate is abbreviated as TPP, rhamnolipid as RHL, chitosan as COS, RHL-COS is rhamnolipid-modified chitosan, glutaraldehyde solution is abbreviated as GA, and magnolol is abbreviated as HNK.

[0035] Example 1: A method for preparing multifunctional magnolol nanoparticles

[0036] Includes the following steps:

[0037] (1) Preparation of RHL-COS nanoparticles:

[0038] 1 mL of sodium tripolyphosphate (TPP) and 2.5 mL of rhamnolipid (RHL, 1 mg / mL) were added dropwise to 5 mL of chitosan solution (0.1 mg / mL), and stirred overnight for 12 h. Then, 100 μL of glutaraldehyde solution (GA, 0.5 wt%) was added dropwise to the mixture, and stirring was continued for 12 h. The formulation was then dialyzed in pH 7.4 phosphate buffer for 24 h to obtain RHL-COS nanoparticles.

[0039] (2) Preparation of HNK@RHL-COS nanoparticles:

[0040] HNK solution (1 mg / mL) was added dropwise to RHL-COS obtained in (1), stirred for 24 h, and sonicated with a probe; and dialyzed in PBS at pH 7.4 for 24 h to remove unencapsulated drug, thus obtaining nanoparticles.

[0041] Examples 2-5

[0042] Except for the different COS:TPP addition ratio, the other preparation conditions are the same as in Example 1.

[0043] Table 1 Results of TPP addition ratios at different COS:

[0044]

[0045] The results of different addition ratios are shown in Table 1. As the COS:TPP ratio increases, the HNK drug loading and encapsulation first decrease, and then increase.

[0046] Examples 6-9

[0047] Except for the different COS:RHL addition ratio, the other preparation conditions are the same as in Example 1.

[0048] Table 2 Prescriptions for Examples 6-9

[0049]

[0050] The results of different COS:RHL addition ratios are shown in Table 2. As the COS:RHL ratio increases, the HNK drug loading gradually increases.

[0051] Examples 10-12

[0052] Except for the different COS:GA addition ratio, the other preparation conditions are the same as in Example 1.

[0053] Table 3 Results of different COS:GA addition ratios

[0054]

[0055] The results of different COS:GA addition ratios are shown in Table 3. As the COS:GA ratio increases, the HNK drug loading and encapsulation efficiency gradually decrease.

[0056] Examples 13-16

[0057] Except for the different COS:HNK addition ratio, the other preparation conditions are the same as in Example 1.

[0058] Table 4 Results of HNK addition ratios at different COS levels

[0059]

[0060] The results of the HNK addition ratio are shown in Table 4. As the COS:HNK ratio increases, the HNK drug loading gradually decreases, and the encapsulation first increases and then decreases.

[0061] The following experiments will be conducted to prepare nanoparticles in Example 1 according to the present invention;

[0062] 1. Characterization Analysis

[0063] The present invention characterizes the nanoparticles prepared in Example 1. Specifically, the morphology of the nanoparticles was examined using transmission electron microscopy (TEM); the particle size and potential of the nanoparticles were detected using a Malvern nanoparticle size analyzer; the particle size changes of the nanoparticles at 4°C, room temperature, and 10% FBS were examined to assess the stability of the nanoparticles; the interaction between RHL and COS in the nanoparticles was analyzed using infrared spectroscopy and Raman spectroscopy; and the in vitro release behavior of the nanoparticles under different pH conditions was examined.

[0064] Figure 2 These are the results of the nanoparticle characterization study. TEM results show that both RHL-COS and HNK@RHL-COS are uniformly spherical, and the particle size of HNK@RHL-COS is larger. Figure 2 A, B). Particle size analysis showed that the particle size of RHL-COS was approximately 163 ± 32 nm. After loading HNK, the nanoparticle size increased to 194 ± 45 nm (PDI = 0.117 ± 0.027), which is consistent with the TEM results. Figure 2 C). Simultaneously, the potential of the nanoparticles changed from -10.9 mV to -28.5 mV after loading HNK. Figure 2 D). Stability studies showed that the nanoparticles exhibited good stability within the first 21 days at 4°C and room temperature, but aggregated or dissociated between days 21 and 28. Figure 2 E, F). In a simulated serum environment, the nanoparticle size did not change significantly within 24 hours, indicating that the nanoparticles have good blood stability and can reach the treatment site intact and stably. Figure 2G). Furthermore, the formation of amide bonds between chitosan and rhamnolipids was verified by infrared and Raman spectroscopy. RHL-COS and HNK@RHL-COS at 1665 cm⁻¹ -1 A distinct infrared bending vibration peak was observed, and a clear amide bond Raman peak was also observed in the Raman spectrum. Subsequently, the chemical structure of HNK@RHL-COS treated in an acidic environment was characterized using infrared and Raman spectroscopy. FTIR analysis showed that the intensity of the characteristic absorption peak representing the amide bond significantly decreased after acid treatment. Raman spectroscopy further confirmed the structural change, with the corresponding amide bond characteristic Raman peak almost undetectable. Figure 2 H, I). In vitro release assay results showed that HNK@RHL-COS was rapidly released in vitro, releasing over 40% of HNK within the first 2 hours under acidic pH 5.5 conditions, while releasing only about 20% under pH 7.4 conditions. Figure 2 In summary, these results indicate that HNK@RHL-COS exhibits significant pH-responsive characteristics.

[0065] 2. Evaluation of in vitro antibacterial and anti-biofilm properties

[0066] This invention investigated the in vitro anti-MRSA and biofilm effects of the nanoparticles prepared in Example 1. Specifically, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the nanoparticles were determined using the microbroth dilution method and plate counting method; the bactericidal curve of the nanoparticles was also determined; then, the effect of the nanoparticles on the formation of MRSA biofilm and their scavenging effect on mature MRSA biofilm were investigated using the crystal violet assay.

[0067] Figure 3 The results show the in vitro antibacterial and antibiofilm properties of the nanoparticles. In vitro antibacterial tests revealed that the MIC (micronizable value) of free HNK against MRSA was 16 μg / mL, while the MICs of RHL-COS and HNK@RHL-COS against MRSA were 10 μg / mL and 2 μg / mL, respectively. Similarly, the MBC (metabolizable biofilm) assay results showed a similar trend, with MBC values ​​of 3 μg / mL, 15 μg / mL, and 25 μg / mL for HNK@RHL-COS, RHL-COS, and HNK against MRSA, respectively. Figure 3 A, B). These results indicate that the antibacterial activity of HNK@RHL-COS is significantly enhanced, which may be attributed to the synergistic antibacterial effect between HNK and chitosan. Subsequently, the OD values ​​of different concentrations of HNK@RHL-COS, RHL-COS, and HNK were measured every 2 hours. 600The bacterial count was performed on agar plates to further monitor the growth of MRSA. Results showed that at MIC, 2×MIC, and 4×MIC concentrations, the antibacterial effect of HNK@RHL-COS against MRSA increased with prolonged exposure time. Figure 3 (C, D). HNK@RHL-COS at the MIC concentration exhibited the best antibacterial effect within 12 hours, while HNK@RHL-COS at concentrations of 2×MIC and 4×MIC achieved significant antibacterial effects within 8 hours. These results indicate that HNK@RHL-COS has a significant inhibitory effect on the growth of MRSA.

[0068] The results of the study on the effect of nanoparticles on biofilm formation showed that, in the concentration range of 1 / 4×MIC to 4×MIC, the OD of HNK@RHL-COS was [data missing]. 570 The value was significantly lower than that of the control group (p<0.05), indicating that it has a significant inhibitory effect on biofilm formation. Figure 3 E). In contrast, the RHL-COS and HNK groups showed limited inhibitory effects on MRSA biofilm formation. The results of the nanoparticle effect assay on mature biofilms showed that, within the concentration range of 1 / 2×MIC to 4×MIC, HNK@RHL-COS exhibited a significant dose-dependent inhibitory effect on mature biofilms. Figure 3 F). A slight anti-biofilm effect was observed only in the RHL-COS and HNK groups at concentrations ≥MIC. In conclusion, HNK@RHL-COS not only inhibits biofilm formation in vitro but also disrupts mature biofilms.

[0069] 3. In vitro and in vivo safety assessment

[0070] This invention conducted in vitro and in vivo safety assessments on the nanoparticles prepared in Example 1, and further investigated their biocompatibility. The blood safety of the nanoparticles was examined through a hemolysis test; the in vitro cytotoxicity of the nanoparticles was examined through a CCK8 assay; and the in vivo safety was assessed by intravenous injection of the nanoparticles into mice and H&E staining analysis of their major organs.

[0071] Figure 4 These are the results of in vitro and in vivo safety tests of the nanoparticles. The hemolysis test results showed that at the MIC concentration, the hemolysis rate of HNK@RHL-COS was less than 5%, indicating that HNK@RHL-COS has good biocompatibility. Figure 4 A, B). The CCK-8 assay results showed that when the HNK@RHL-COS concentration was below 2×MIC, the cell viability of L929 cells was greater than 80%, while after treatment with both HNK and RHL-COS, the cell viability was below 50%. Figure 4C, D). H&E staining results of mouse tissues and organs showed that after treatment with HNK@RHL-COS, RHL-COS, and HNK, no significant pathological changes were observed in the heart, liver, lungs, kidneys, and spleen of mice. Figure 4 E). In summary, these results indicate that HNK@RHL-COS exhibits good biocompatibility both in vivo and in vitro.

[0072] 4. Evaluation of in vivo antibacterial properties

[0073] The present invention evaluated the in vivo antibacterial properties of the nanoparticles prepared in Example 1. First, the therapeutic effect of the nanoparticles on a mouse model of MRSA wound infection was investigated; then, the therapeutic effect of the nanoparticles on a mouse model of peritonitis was investigated.

[0074] Figure 5 To investigate the therapeutic effect of multifunctional magnolol nanoparticles on a mouse wound model of MRSA infection, a mouse skin infection model was first constructed. Figure 5 A). The results showed that the mice in the HNK@RHL-COS group had the fastest wound healing rate, with the wound area reduced to less than 50% of the initial wound area by day 2. Figure 5 (B, C). In the RHL-COS group, the wound area decreased to 50% of its original size by day 5. Compared with the HNK group, the wound healing rate in the HNK@RHL-COS group was significantly faster, which may be due to its improved permeability and synergistic antibacterial effect. Bacterial load assay results showed that the bacterial load in the model group was significantly higher than that in other groups throughout the treatment period (p<0.05). Figure 5 D, 5E). The bacterial load in the HNK@RHL-COS, RHL-COS, and HNK groups was significantly lower than that in the model group (p<0.05). In particular, the HNK@RHL-COS group showed the fastest decrease in bacterial load, and after 7 days of treatment, the HNK@RHL-COS group had the lowest bacterial load. Figure 5 F). In summary, HNK@RHL-COS can significantly kill bacteria at the site of infection and promote wound healing.

[0075] Masson staining results showed that the model group mice had less collagen content at the wound site, and the collagen arrangement was significantly loose. Figure 5 G). In the HNK@RHL-COS group, the collagen in the wounds of mice was darker, more abundant, and more neatly arranged and denser. This indicates that the skin structure in the HNK@RHL-COS group was reconstructed and improved. H&E staining of the wound tissue showed that the model group had a large number of inflammatory cell infiltrations, while the treatment group showed a significant reduction in inflammatory cell infiltrations at the infection site. Figure 5G). ELISA results showed that the serum levels of inflammatory factors IL-6, IL-1β, TNF-α, and NO in the model group mice were significantly higher than those in the control group (p<0.05). After HNK@RHL-COS treatment, the levels of inflammatory factors were significantly downregulated (p<0.001). Figure 5 (HK). In summary, HNK@RHL-COS can effectively relieve inflammation caused by MRSA infection and promote wound healing.

[0076] Next, a bacterial peritonitis model was constructed to evaluate the therapeutic effect of HNK@RHL-COS on systemic MRSA infection. Figure 6 A). The results showed that the total bacterial load, extracellular bacteria, and intracellular bacteria count in the ascites fluid of mice in each group were significantly reduced, and significantly lower than those in the model group (p<0.001). Figure 6 (B, C, and D), among which HNK@RHL-COS showed the best antibacterial effect. H&E staining results showed that in the model group and the RHL-COS group, some hepatocytes showed necrosis, and a few renal tubular epithelial cells showed degeneration and necrosis. Figure 6 E). Both the model group and the HNK group showed increased alveolar epithelial cells and aggravated pulmonary interstitial fibrosis. In contrast, no significant pathological changes were observed in the HNK@RHL-COS group and the control group. ELISA results showed that, compared with the control group, the serum levels of inflammatory factors IL-6, IL-1β, TNF-α, and NO in the model group mice were significantly increased (p<0.001), while the HNK@RHL-COS, RHL-COS, and HNK treatment groups significantly reduced these inflammatory factors (p<0.001). Figure 6 (FI). In summary, HNK@RHL-COS effectively reduced inflammation and related inflammatory damage in mice with bacterial peritonitis.

[0077] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A multifunctional honokiol nanoparticle, characterized in that, The magnolol nanoparticles were prepared by loading magnolol onto rhamnolipid-modified chitosan as a carrier.

2. The method for preparing magnolol nanoparticles as described in claim 1, characterized in that, Includes the following steps: (1) Add sodium polyphosphate and rhamnolipin solution dropwise to chitosan solution and stir; (2) Add glutaraldehyde solution dropwise to the mixed solution obtained in step (1) and stir to crosslink; dialyze the resulting solution in PBS at pH 7.4 to obtain rhamnolipin-chitosan solution; (3) Add the honokiol solution dropwise to the rhamnolipin-chitosan solution obtained in step (2), stir, and sonicate with a probe; and dialyze in PBS at pH 7.4 to remove unencapsulated drug, thus obtaining honokiol nanoparticles.

3. The method for preparing magnolol nanoparticles as described in claim 2, characterized in that, The volume ratio of chitosan, rhamnolipid, and sodium polyphosphate in step (1) is 1:(0.17-1):(0.1-0.5), and the dropping rate is 1 drop / s.

4. The method for preparing magnolol nanoparticles as described in claim 2, characterized in that, In step (2), the volume ratio of glutaraldehyde solution to the mixed solution obtained in step (1) is 1:(50-100), and the dropping rate is 1 drop / s.

5. The method for preparing magnolol nanoparticles as described in claim 2, characterized in that, In step (3), the volume ratio of magnolol solution to rhamnolipin-chitosan solution is 1:(2-15); the ultrasonic power is 10-50kHz and the ultrasonic time is 1-5min.

6. The application of the magnolol nanoparticles as described in claim 1 or the magnolol nanoparticles prepared by the preparation method according to any one of claims 2-5 in the preparation of antibacterial drugs.

7. The use of the magnolol nanoparticles as described in claim 1 or the magnolol nanoparticles prepared by the preparation method according to any one of claims 2-5 in the preparation of drugs for treating inflammatory / infectious diseases.

8. The application as described in claim 7, characterized in that, The inflammatory / infectious diseases mentioned include one or more of wound infections, bacterial pneumonia, and peritonitis.

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