A method for preparing large quantities of polymer vesicles with uniform particle size by hydrothermal method

Abstract

The present invention belongs to the field of polymer materials, and specifically relates to a polymer vesicle that can be formed in batches by self-assembly of an amphiphilic block copolymer with uniform particle size and stability, and a preparation method thereof, specifically comprising weighing an amphiphilic block copolymer, dissolving it in an organic reagent, mixing it evenly, adding water and heating it to obtain a uniform vesicle. The preparation process of the present invention is simple and feasible, has high production efficiency and good repeatability, and is suitable for large-scale promotion of a preparation method for polymer vesicles with uniform and controllable particle size.

Description

Technical Field

[0001] The present invention belongs to the field of polymer materials, and relates to a universal method for preparing polymer vesicles with uniform particle size distribution in batches, and specifically relates to a polymer vesicle with uniform particle size and stability formed in batches by self-assembly of an affinity block copolymer, and a preparation method thereof. Technical Background

[0002] With the rapid development and increasing maturity of nanotechnology, it has shown unprecedented application potential in the field of medicine. In recent years, nanomedicine has become a new hot spot in the field of medical research. Among them, the specific advantages of nanomedicine delivery have attracted more and more attention from medical workers. Therefore, with the development of nanotechnology and new drug research, a number of nanomedicines with special effects will be successfully developed, such as targeted drugs, sustained-release or controlled-release drugs, prolonging the drug action time, changing the mode of action or route of administration, reducing or avoiding adverse reactions, etc., which will provide a new direction for drug research.

[0003] As hollow spheres composed of amphiphilic molecules self-assembled, polymer vesicles are generally between tens of nanometers and tens of micrometers in size. Their "shell-core" nanostructure has higher stability, and the membrane structure is easier to modify and graft various functional groups to achieve functionalization and intelligence. In addition, polymer vesicles have similar functions to liposomes, and are biodegradable, water-soluble, biocompatible, biomimetic, and storage stable, making them ideal drug delivery materials. The surface can be easily modified into additional targets, which enables them to deliver drugs, proteins, and genetic materials to target tissues, playing an important role in cancer medicine, gene therapy, and diagnosis. They can load unstable biomacromolecules (including proteins, drugs, genes) and prevent degradation, and can be endocytosed by cells to complete drug molecule therapy. However, traditional methods include: emulsification (solvent replacement or diffusion), nanoprecipitation, ion gelation, and microfluidics. The particle size distribution of the prepared polymer vesicles is relatively wide, and subsequent biodrug loading and ensuring that the quality and performance of different batches of products are basically the same have become important issues that need to be solved.

[0004] Therefore, the large-scale, batch-scale engineering and controllable preparation of polymer vesicles with uniform particle size has always been a key research focus and market application in the field of drug carriers. Summary of the invention

[0005] The primary purpose of the present invention is to overcome the shortcomings and deficiencies of the existing preparation of polymer vesicles, and to prepare polymer vesicles with uniform and stable particle sizes in batches and on a large scale through a hydrothermal method, thereby providing a method for preparing uniform vesicles.

[0006] Another object of the present invention is to provide applications of the above-mentioned uniform vesicles.

[0007] The purpose of the present invention is achieved through the following technical solutions:

[0008] A method for preparing homogenized vesicles comprises the following steps:

[0009] The amphiphilic block copolymer is weighed and dissolved in an organic reagent and mixed evenly, and then water is added and heated to obtain uniform vesicles.

[0010] The amphiphilic block copolymer is one of PEGx-b-PCLy or PEGx-b-PLAy; wherein x is 3000 to 8000, y is 2000 to 95000, preferably PEG 5000 -b-PLA 12000 ;

[0011] The organic reagent in S1 is at least one of tetrahydrofuran (THF), 1,4-dioxane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), dichloromethane (DCM), chloroform (CHCl3), methylacetate, acetonitrile, ethanol, methyl isobutyl ketone (MIBK), hexafluoroisopropanol (HFIP), acetone and petroleum ether, preferably tetrahydrofuran (THF) and 1,4-dioxane. The volume ratio of tetrahydrofuran to 1,4-dioxane is 1 to 5: 1 to 5, preferably 3: 2.

[0012] The mass volume ratio of the amphiphilic block copolymer to the organic solvent is 0.1-50 mg:0.1-50 mL, preferably 10-50 mg:5-20 mL, and more preferably 50 mg:10 mL.

[0013] The uniform mixing is preferably performed by stirring at a rotation speed of 200-2000 rpm, preferably 700 rpm.

[0014] The volume ratio of water to organic solvent is 1-100:0.4-50, preferably 30-60:2-20, and more preferably 40-60:2-10.

[0015] The heating temperature is 50-200° C., preferably 80-150° C., more preferably 100° C. The heating time is 0.5-12 h, preferably 1-5 h, more preferably 2 h.

[0016] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0017] (1) The preparation process of the present invention is simple and feasible, with high production efficiency and good repeatability, and is suitable for large-scale promotion of the preparation method of polymer vesicles with uniform and controllable particle size.

[0018] (2) The preparation method of the present invention can be used for engineering and promotion of polymer vesicle nanocarriers, drug controlled release and nanoreactor related fields. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 is a transmission electron microscope image of the polymer vesicle corresponding to Example 1 of the present invention;

[0020] Example 1

[0021] 50 mg of amphiphilic block copolymer PEG 5000 -b-PLA 12000 Dissolve in 10mL of an organic solvent with a ratio of 3:2 of tetrahydrofuran and dipentane, then use a magnetic stirrer at a stirring rate of 700rpm to completely dissolve, and then transfer the solution to a hydrothermal reactor lined with polytetrafluoroethylene. Then add 50mL of ultrapure water and quickly put it into a drying oven preset at 100°C for hydrothermal reaction for 2h. After the reaction is completed, cool the hydrothermal reaction system to room temperature to obtain polymer vesicles with uniform particle size.

[0022] Example 2

[0023] 40 mg of amphiphilic block copolymer PEG 5000 -b-PLA 12000 Dissolve in 5 mL of an organic solvent with a ratio of tetrahydrofuran to dipentane of 3:2, then use a magnetic stirrer at a stirring rate of 700 rpm to completely dissolve, and then transfer the solution to a hydrothermal reactor lined with polytetrafluoroethylene. Then add 50 mL of ultrapure water, quickly put it into a drying oven preset at 80°C, and hydrothermally react for 4 hours. After the reaction is completed, the hydrothermal reaction system is cooled to room temperature to obtain polymer vesicles with uniform particle size, and the morphology is similar to that of Example 1.

[0024] Example 3

[0025] 40 mg of amphiphilic block copolymer PEG 5000 -b-PLA 12000 Dissolve in 10 mL of an organic solvent with a ratio of tetrahydrofuran to dipentane of 3:2, then use a magnetic stirrer at a stirring rate of 700 rpm to completely dissolve, and then transfer the solution to a hydrothermal reactor lined with polytetrafluoroethylene. Then add 50 mL of ultrapure water, quickly put it into a drying oven preset at 100°C, and hydrothermally react for 2 hours. After the reaction is completed, the hydrothermal reaction system is cooled to room temperature to obtain polymer vesicles with uniform particle size, and the morphology is similar to that of Example 1.

[0026] Example 4

[0027] 30 mg of amphiphilic block copolymer PEG 5000 -b-PLA 12000 Dissolve in 10 mL of an organic solvent with a ratio of tetrahydrofuran to dipentane of 3:2, then use a magnetic stirrer at a stirring rate of 700 rpm to completely dissolve, and then transfer the solution to a hydrothermal reactor lined with polytetrafluoroethylene. Then add 50 mL of ultrapure water, quickly put it into a drying oven preset at 120°C, and hydrothermally react for 1 hour. After the reaction is completed, the hydrothermal reaction system is cooled to room temperature to obtain polymer vesicles with uniform particle size, and the morphology is similar to that of Example 1.

[0028] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for preparing uniform vesicles, characterized in that The method comprises the following steps: weighing an amphiphilic block copolymer, dissolving it in an organic reagent and mixing it evenly, transferring the solution to a hydrothermal reactor lined with polytetrafluoroethylene, adding water and heating it to obtain uniform vesicles; The amphiphilic block copolymer is PEG 5000 -b-PLA 12000 ; The organic reagent is a mixture of tetrahydrofuran and dipentane, and the volume ratio of tetrahydrofuran to dipentane is 3:

2.

2. The method according to claim 1, characterized in that: The mass volume ratio of the amphiphilic block copolymer to the organic solvent is 0.1-50 mg:0.1-50 mL.

3. The method according to claim 1, characterized in that: The mass volume ratio of the amphiphilic block copolymer to the organic solvent is 10-50 mg:5-20 mL.

4. The method according to claim 1, characterized in that: The volume ratio of water to organic solvent is 1-100:0.4-50.

5. The method according to claim 1, characterized in that: The heating temperature is 50-200° C., and the heating time is 0.5-12 h.

6. The method according to claim 1, characterized in that: The uniform mixing is carried out by stirring at a rotation speed of 200-2000 rpm.

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