Drug loading system of COF nano-drug carrier and preparation method of drug loading system

Abstract

The invention discloses a drug loading system of a COF nano-drug carrier and a preparation method of the drug loading system. The method comprises the following steps: 1, synthesizing COF nanoparticles; furthermore, synthesis is performed through the following steps: S11, mixing TAPB and DMTPA, and adding a mixed solvent of mesitylene and 1, 4-dioxane, which is sufficient for dissolving TAPB and DMTPA; s12, adding an acetic acid catalyst, and sealing the reaction container; s13, under the condition of constant temperature and humidity, solvothermal reaction is carried out for 72 hours, and by optimizing the COF synthesis condition and the drug loading process, the high drug loading capacity is achieved, so that the effective utilization degree of the drug is improved; the COF nano-drug carrier prepared by the invention has controllable drug release performance, and the release rate and duration of the drug can be adjusted according to treatment requirements.

Description

Technical Field

[0001] The present invention relates to a drug-loading system of a COF nano-drug carrier and a preparation method thereof, belonging to the field of... Background Art

[0002] In drug delivery systems, nano-drug carriers have received extensive attention due to their unique physical and chemical properties, as well as their ability to improve drug solubility, stability, and bioavailability. Traditional nano-drug carriers, such as liposomes, polymer nanoparticles, and inorganic nanoparticles, have achieved significant success clinically. However, these carriers still face some challenges in aspects such as drug loading capacity, biocompatibility, and controllable drug release.

[0003] Covalent organic frameworks (COFs), as a class of emerging nanomaterials, have regular pore structures, high specific surface areas, and excellent chemical stability, which make them potential drug carriers. COFs can be formed by covalent bonds between precisely designed organic monomers, allowing for fine-tuning of pore size and shape to match different drug molecules. In addition, the porous structure of COFs provides the possibility of high drug loading capacity, and the functional groups on their surfaces can be used for targeted drug delivery and controllable release.

[0004] However, despite the great potential of COFs as drug carriers, research on their practical applications, especially in drug-loading systems and preparation methods, is still limited. Therefore, developing a COF-based nano-drug carrier and its drug-loading system and optimizing its preparation method to improve drug loading efficiency and stability have important research significance and practical application value. Summary of the Invention

[0005] Aiming at the deficiencies of the existing technology, the purpose of the present invention is to provide a drug-loading system of a COF nano-drug carrier and a preparation method thereof to solve the problems.

[0006] To achieve the above purpose, the present invention is realized through the following technical solutions: A drug-loading system of a COF nano-drug carrier and a preparation method thereof, including the following steps:

[0007] Step 1: Synthesize COF nanoparticles;

[0008] Further, it is synthesized through the following steps:

[0009] S11: Mix TAPB and DMTPA, and add a mixed solvent of mesitylene and 1,4-dioxane that is sufficient to dissolve TAPB and DMTPA;

[0010] S12: Add an acetic acid catalyst and seal the reaction vessel;

[0011] S13. Conduct a solvothermal reaction for 72 hours under constant temperature and humidity conditions.

[0012] S14. After the reaction, collect the product by centrifugation and wash it repeatedly with absolute ethanol and deionized water to remove unreacted raw materials and impurities.

[0013] S15. Dry the product in a vacuum drying oven to obtain porous COF nanoparticles.

[0014] Step Two. Prepare an adriamycin drug-loading system.

[0015] Further, it is prepared through the following steps:

[0016] S21. Dissolve adriamycin in phosphate buffer to form a drug solution.

[0017] S22. Disperse the COF nanoparticles prepared in Step One in another portion of phosphate buffer to form a uniform suspension.

[0018] S23. Mix the drug solution prepared in S21 with the COF nanoparticle suspension prepared in S22 and gently shake it in a constant temperature shaker to allow adriamycin molecules to be loaded onto the COF nanoparticles by physical adsorption.

[0019] S24. After the loading is completed, collect the drug-loading system by centrifugation and wash it with phosphate buffer to remove unloaded adriamycin.

[0020] S25. Dry the drug-loading system in a vacuum drying oven to obtain an adriamycin drug-loading system of COF.

[0021] Preferably, in Step S11, 1,3,5-tris(4-aminophenyl)benzene is selected as TAPB, and 2,5-dimethoxyterephthalaldehyde is selected as DMTPA as organic monomers for constructing COF nanoparticles.

[0022] Preferably, TAPB and DMTPA are mixed in a molar ratio of 1:2.

[0023] Preferably, in Step S11, the volume ratio of mesitylene to 1,4-dioxane is 1:1.

[0024] Preferably, in Step S12, the concentration of the acetic acid catalyst is 6M.

[0025] Preferably, in Step S13, the conditions of constant temperature and humidity are that the temperature is controlled at 25 °C and the relative humidity is controlled at 50%.

[0026] Preferably, in Step S21, the loading amount of adriamycin accounts for 5% to 20% of the mass of the COF nanoparticles.

[0027] Preferably, in step S24, washing is performed through the following steps:

[0028] S241. Use a phosphate buffer solution with a pH of 7.4 to redisperse the drug-loaded system precipitate obtained by centrifugation in PBS to form a suspension;

[0029] S242. Gently shake or oscillate the suspension to promote the release and diffusion of the non-loaded doxorubicin into the phosphate buffer solution;

[0030] S243. Perform centrifugal separation again to separate the washed drug-loaded system from the phosphate buffer solution;

[0031] S244. Repeat steps S241 - S243 multiple times, centrifuge to collect the washed drug-loaded system, and then perform vacuum drying to remove residual moisture and solvents.

[0032] The present invention also provides a drug-loaded system of a COF nanodrug carrier prepared by the above method.

[0033] Beneficial effects

[0034] By optimizing the synthesis conditions of COF and the drug loading process, the present invention achieves a high drug loading amount, thereby improving the effective utilization rate of the drug; the COF nanodrug carrier prepared by the present invention has controllable drug release performance, and the drug release rate and duration can be adjusted according to treatment requirements. Specific embodiments

[0035] To make the technical means, creative features, achieved purposes and effects of the present invention easy to understand, the present invention will be further described below in conjunction with specific embodiments.

[0036] Example 1

[0037] Prepare the following materials: 1.0 g of TAPB, 2.0 g of DMTPA, 50 ml of mesitylene, 50 ml of 1,4-dioxane, 10 ml of acetic acid (concentration 6 M), and an appropriate amount of doxorubicin (calculated according to 10% of the mass of the COF nanoparticles).

[0038] Preparation process: 1. Mix TAPB and DMTPA, and add them to the mixed solvent of mesitylene and 1,4-dioxane, and stir evenly.

[0039] 2. Add an acetic acid catalyst and seal the reaction vessel.

[0040] 3. Carry out a solvothermal reaction for 72 hours under the conditions of 25 °C and 50% relative humidity.

[0041] 4. After the reaction is completed, the product is collected by centrifugation and washed repeatedly with absolute ethanol and deionized water to remove unreacted raw materials and impurities.

[0042] 5. The product is dried in a vacuum drying oven to obtain porous COF nanoparticles.

[0043] 6. Doxorubicin is dissolved in phosphate buffer (PBS) to form a drug solution.

[0044] 7. The COF nanoparticles are dispersed in another portion of PBS to form a homogeneous suspension.

[0045] 8. The drug solution is mixed with the COF nanoparticle suspension and gently shaken in a thermostatic shaker to load doxorubicin molecules onto the COF nanoparticles.

[0046] 9. After the loading is completed, the drug-loaded system is collected by centrifugation and washed with PBS to remove unloaded doxorubicin.

[0047] 10. The drug-loaded system is dried in a vacuum drying oven to obtain a COF-based doxorubicin drug-loaded system.

[0048] Preparation conditions: temperature 25 °C, relative humidity 50%, solvothermal reaction time 72 hours.

[0049] Results: A COF-based doxorubicin drug-loaded system was successfully prepared with high drug loading efficiency and controllable drug release.

[0050] Comparative Example 1

[0051] The difference from Example 1 is that 2.0 g of DMTPA is changed to 1.5 g of DMTPA;

[0052] The preparation process and conditions are the same as those in Example 1.

[0053] Results: Although the drug-loaded system can be successfully prepared, the drug loading efficiency is slightly lower than that in Example 1 due to the change in the COF structure caused by the reduction in the amount of DMTPA used.

[0054] Comparative Example 2

[0055] The difference from Example 1 is that 50 ml of mesitylene is changed to 75 ml and 50 ml of 1,4-dioxane is changed to 25 ml.

[0056] The preparation process and conditions are the same as those in Example 1.

[0057] Results: The preparation process of the drug-loaded system is affected by the solvent ratio, resulting in a decrease in drug loading efficiency and a slight decrease in the dispersibility and stability of the COF nanoparticles.

[0058] Comparative Example 3

[0059] The difference from Example 1 is that the concentration of acetic acid is adjusted to 3M.

[0060] The preparation process and conditions are the same as those in Example 1.

[0061] Result: The synthesis of COF nanoparticles is affected by the concentration of acetic acid, resulting in a decrease in the drug loading efficiency and stability of the drug delivery system, and the COF structure is not complete enough.

[0062] The following Table 1 shows exemplary experimental data:

[0063]

[0064] Remarks:

[0065] Expected drug loading: The expected drug loading amount calculated based on the mass of COF nanoparticles and the preset drug loading percentage.

[0066] Actual drug loading: The actual drug loading amount measured through existing test experiments.

[0067] Drug loading efficiency: The percentage ratio of the actual drug loading amount to the expected drug loading amount, indicating the efficiency of successfully loading the drug into COF nanoparticles.

[0068] Drug release stability: Under simulated physiological conditions, after a certain period of time (such as 24 hours), the stability percentage of the drug released from COF nanoparticles. This is calculated by measuring the ratio of the amount of drug remaining in the nanoparticles after release to the initial loading amount.

[0069] The foregoing has shown and described the basic principles, main features and advantages of the present invention. For those skilled in the art, it is obvious that the present invention is not limited to the details of the above-described exemplary embodiments, and without departing from the spirit or basic characteristics of the present invention, the present invention can be implemented in other specific forms. Therefore, in any aspect, the embodiments should be regarded as exemplary and non-limiting. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, it is intended to embrace all changes falling within the meaning and scope of the equivalent elements of the claims in the present invention. Any reference signs in the claims should not be regarded as limiting the claimed claim.

[0070] In addition, it should be understood that although this specification is described in terms of embodiments, not every embodiment only contains an independent technical solution. This narrative manner of the specification is only for clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A preparation method of a drug-loading system of a COF nano-drug carrier, characterized in that: It includes the following steps: Step 1, synthesize COF nanoparticles; Further, it is synthesized through the following steps: S11. Mix TAPB and DMTPA, and add a mixed solvent of mesitylene and 1,4-dioxane sufficient to dissolve TAPB and DMTPA; S12. Add an acetic acid catalyst and seal the reaction vessel; S13. Under the conditions of constant temperature and humidity, carry out a solvothermal reaction for 72 hours; S14. After the reaction, collect the product by centrifugation, and wash it repeatedly with anhydrous ethanol and deionized water to remove unreacted raw materials and impurities; S15. Dry the product in a vacuum drying oven to obtain porous COF nanoparticles; Step 2, prepare an adriamycin drug-loading system; Further, it is prepared through the following steps: S21. Dissolve adriamycin in phosphate buffer to form a drug solution; S22. Disperse the COF nanoparticles prepared in Step 1 in another portion of phosphate buffer to form a uniform suspension; S23. Mix the drug solution prepared in S21 with the COF nanoparticle suspension prepared in S22, and gently shake it in a constant temperature shaker to load adriamycin molecules onto the COF nanoparticles by physical adsorption; S24. After the loading is completed, collect the drug-loading system by centrifugation, and wash it with phosphate buffer to remove unloaded adriamycin; S25. Dry the drug-loading system in a vacuum drying oven to obtain an adriamycin drug-loading system of COF.

2. The preparation method of a drug-loading system of a COF nanodrug carrier according to claim 1, characterized in that: In Step S11, 1,3,5-tris(4-aminophenyl)benzene is selected as TAPB, and 2,5-dimethoxyterephthalaldehyde is selected as DMTPA as organic monomers for constructing COF nanoparticles.

3. The preparation method of a drug-loading system of a COF nano-drug carrier according to claim 2, wherein: TAPB and DMTPA are mixed in a molar ratio of 1:

2.

4. The preparation method of a drug-loading system of a COF nano-drug carrier according to claim 1, characterized in that: In Step S11, the volume ratio of mesitylene to 1,4-dioxane is 1:

1.

5. The preparation method of a drug-loading system of a COF nano-drug carrier according to claim 1, characterized in that: In Step S12, the concentration of the acetic acid catalyst is 6M.

6. The preparation method of a drug-loading system of a COF nano-drug carrier according to claim 1, characterized in that: In Step S13, the conditions of constant temperature and humidity are that the temperature is controlled at 25°C and the relative humidity is controlled at 50%.

7. The preparation method of a drug-loading system of a COF nanodrug carrier according to claim 1, characterized in that: In Step S21, the loading amount of adriamycin accounts for 5% to 20% of the mass of COF nanoparticles.

8. The preparation method of a drug-loading system of a COF nanodrug carrier according to claim 1, characterized in that: In Step S24, the washing is carried out through the following steps: S241. Use phosphate buffer with pH 7.4 to redisperse the centrifuged drug-loading system precipitate in PBS to form a suspension; S242. Gently shake or oscillate the suspension to promote the release and diffusion of unloaded adriamycin into the phosphate buffer; S243. Centrifuge again to separate the washed drug-loading system from the phosphate buffer; S244. Repeat Steps S241 - S243 multiple times, centrifuge to collect the washed drug-loading system, and then carry out vacuum drying to remove residual moisture and solvent.

9. A drug-loading system of a COF nanodrug carrier prepared by the method according to any one of claims 1 to 8.

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