A method for preparing hydrophilic drug nanoliposomes based on a microfluidic-low shear coupling double emulsion method and hydrophilic drug nanoliposomes
The preparation of nanoliposomes by microfluidic-low-shear coupling multiple emulsion method solves the problem of low encapsulation efficiency of water-soluble macromolecular drugs and achieves improved particle size uniformity and high encapsulation efficiency.
Patent Information
- Application Number
- CN202610710407.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-05-22
- Publication Date
- 2026-06-26
AI Technical Summary
Existing technologies are insufficient for efficiently encapsulating water-soluble macromolecular drugs such as Ganoderma lucidum polysaccharides. Traditional methods result in low encapsulation rates, uneven particle sizes, and easy damage to the drug structure.
The microjet-low-shear coupling double emulsion method was adopted. The oil phase was injected by micron-level jet and combined with low-speed stirring to form a uniform W/O primary emulsion, then a W/O/W double emulsion was formed, and finally the solvent was removed by vacuum evaporation to prepare nanoliposomes.
The particle size of Ganoderma lucidum polysaccharide nanoliposomes was controlled at 200-300 nm, with a polydispersity index of about 0.2 and an encapsulation efficiency of over 70%, which significantly improved the encapsulation efficiency and stability.
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Figure CN122272506A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical technology, specifically to a method for preparing hydrophilic drug nanoliposomes based on microfluidic-low shear coupling emulsification and the hydrophilic drug nanoliposomes themselves. Background Technology
[0002] Hydrophilic drugs, such as Ganoderma lucidum polysaccharides, are hydrophilic macromolecules with a molecular weight typically around 10. 3 -10 6 Between 100 and 1000 mg / day, after oral administration, it is difficult to cross the intestinal epithelial barrier, resulting in extremely low bioavailability, which has become a bottleneck problem restricting its clinical application.
[0003] Nanoliposomes, as vesicle carriers composed of phospholipid bilayers, possess unique hydrophilic cores and hydrophobic bilayer structures, enabling them to simultaneously encapsulate water-soluble and lipid-soluble drugs. They also offer advantages such as good biocompatibility, targeted delivery, and controlled release, making them ideal carriers for improving the bioavailability of natural active ingredients. Currently, the main methods for preparing nanoliposomes include thin-film hydration, reverse evaporation, organic solvent injection, and double emulsion. Among these, thin-film hydration is the most widely used due to its simplicity and absence of organic solvent residue.
[0004] Currently, ultrasound-assisted thin-film hydration is commonly used to prepare Ganoderma lucidum polysaccharide liposomes. First, soybean lecithin is dissolved in chloroform, then rotary evaporated to form a dried phospholipid membrane. Next, a Ganoderma lucidum polysaccharide solution is added and ultrasonically hydrated. Because the Ganoderma lucidum polysaccharide dissolves in the external aqueous phase, only a very small portion is encapsulated within the aqueous phase of the liposome, resulting in an encapsulation efficiency of only about 30%. Furthermore, this figure includes polysaccharides adsorbed on the liposome surface, making the actual encapsulation efficiency even lower. This limitation is an inherent problem with the thin-film hydration method for encapsulating water-soluble drugs—the proportion of the internal aqueous phase to the total volume is extremely small, naturally limiting drug loading efficiency.
[0005] Furthermore, the traditional shear homogenization method involves directly dripping the aqueous phase into the oil phase and breaking it down by stirring. This results in uneven particle size, unstable initial emulsion, and generally requires a shear rate of over 20,000 rpm, which can easily damage the structure of large molecule drugs. Shear rates below 20,000 rpm result in low emulsification efficiency, large particle size, and low encapsulation rate. Summary of the Invention
[0006] To address the aforementioned technical problems, the present invention aims to provide a method for preparing hydrophilic drug nanoliposomes based on microfluidic-low-shear coupling emulsification, and the hydrophilic drug nanoliposomes themselves. This method utilizes microfluidic pre-structuring to significantly reduce the energy threshold required for emulsification, achieving efficient nano-sizing at only 3000-7000 rpm, thus maximizing the protection of the structural integrity of the macromolecular drug (Ganoderma lucidum polysaccharide).
[0007] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing hydrophilic drug nanoliposomes based on microfluidic-low shear coupling emulsification, characterized in that the preparation is carried out according to the following method:
[0008] (1) Prepare aqueous solutions of hydrophilic drugs and chloroform solutions of soybean lecithin separately;
[0009] (2) Soybean lecithin chloroform solution was added to the chamber as the oil phase. Microtubes were arranged in the lower part of the chamber. Under low-speed stirring and shearing, the hydrophilic drug aqueous solution was injected into the oil phase in the low-shear stirring field through the microtubes in the form of micron-level jet. After the injection was completed, the stirring was turned off and the W / O colostrum sample was collected.
[0010] (3) The W / O pre-emulsion sample is used as the dispersed phase and injected into the external aqueous phase in the same way as in step (2). After two low-speed stirring and shearing emulsifications, a W / O / W double emulsion is formed.
[0011] (4) Remove chloroform by vacuum evaporation of W / O / W double emulsion to obtain hydrophilic drug nanoliposomes.
[0012] In the above scheme: the hydrophilic drug is Ganoderma lucidum polysaccharide.
[0013] Traditional methods involve directly dripping the aqueous phase into the oil phase and relying on stirring to break up the droplets, resulting in uneven particle size and unstable primary emulsion. This invention employs a microtube micron-level jet for precise injection, producing droplets with small initial size and large specific surface area. Uniform nanoscale W / O primary emulsions can be formed even at low rotation speeds, and the stability of the primary emulsion is significantly superior to conventional methods.
[0014] Furthermore, the droplets formed by low shear and microjets have uniform particle size, making them less prone to demulsification during rotary evaporation to remove solvent, resulting in high encapsulation efficiency and higher storage stability.
[0015] In the above scheme: In step (1), the operation of preparing the hydrophilic drug aqueous solution is as follows: accurately weigh the Ganoderma lucidum polysaccharide powder with a molecular weight of less than 100kDa that has been dried to constant weight, dissolve it with PBS buffer, prepare a 10 mg / mL Ganoderma lucidum polysaccharide solution, and store it at 4°C in the dark for later use.
[0016] In the above scheme, the concentration of soybean lecithin chloroform solution is 10-100 mg / mL.
[0017] In the above scheme, the concentration of soybean lecithin chloroform solution is 20-40 mg / mL.
[0018] In the above scheme: In step (2), the diameter of the microtube is 100-300 μm, the stirring shear rate is 1000-10000 rpm, and the hydrophilic drug aqueous solution is injected using a syringe pump with a flow rate of 0.1-1.0 μL / s. Preferably, the diameter of the microtube is 200 μm. The microtube generates a micron-sized jet, which achieves efficient fragmentation due to its huge specific surface area. Combined with a low shear field, it achieves nanoscale droplets without the need for high pressure and strong shear.
[0019] In the above scheme: the shear stirring speed in step (2) is 3000 rpm, and the injection pump flow rate is 0.2-0.5 uL / s. Ganoderma lucidum polysaccharide is a macromolecular water-soluble polysaccharide. This invention addresses the problems of high shear causing polysaccharide structure damage and low shear resulting in poor encapsulation. It employs low shear throughout the process, using microfluidics to achieve efficient emulsification, protecting the polysaccharide's activity and structural integrity, and improving the encapsulation rate.
[0020] In the above scheme: in step (3), the external aqueous phase is PBS buffer, and the speed of the second low-speed stirring and shearing is 3000-10000 rpm.
[0021] In the above scheme: the speed of the secondary low-speed stirring and shearing is 5000-7000 rpm. In step (4), the vacuum evaporation adopts a gradient vacuum method, and the rotary evaporation is carried out for 30 minutes at absolute pressures of 100 Pa, 75 Pa and 50 Pa respectively. Vacuum rotary evaporation is less likely to break the emulsion.
[0022] Hydrophilic drug nanoliposomes prepared by the method described above based on microfluidic-low shear coupling multiple emulsion.
[0023] Compared with existing technologies, this invention has the following advantages: the Ganoderma lucidum polysaccharide nanoliposomes prepared by this invention have a particle size controlled at 200-300 nm, a polydispersity index of approximately 0.2, and an encapsulation efficiency of over 70%, which is more than twice that of the traditional thin-film hydration method. The microfluidic-low-shear coupled re-emulsification method established in this study effectively solves the technical problem of low encapsulation efficiency of water-soluble macromolecular Ganoderma lucidum polysaccharides.
[0024] The microjets-low shear coupling strategy of this invention effectively reduces the energy threshold required for nanoemulsification. Unlike traditional high-shear homogenization methods that require speeds above 20,000 rpm, this method utilizes a 200 μm diameter microtube to inject the inner aqueous phase into the oil phase in the form of a micron-sized jet. The large specific surface area of the microjets allows for efficient fragmentation into nano-sized droplets at low speeds of 3,000-7,000 rpm, achieving low-damage encapsulation of Ganoderma lucidum polysaccharides. Attached Figure Description
[0025] Figure 1 This is a schematic diagram of the process of the present invention.
[0026] Figure 2The effect of the first injection flow rate on W / O colostrum particle size, PDI, and appearance is shown. (a) is a bar graph of particle size + PDI, and (b) is a photograph of the sample appearance.
[0027] Figure 3 The effect of stirring speed on W / O pre-emulsion particle size, PDI, and appearance is shown. (a) is a bar graph of particle size + PDI, and (b) is a photograph of the sample appearance.
[0028] Figure 4 The effect of stirring speed on particle size, PDI and appearance of W / O / W double emulsion. (a) is a bar graph of particle size + PDI, (b) is a photograph of the sample appearance.
[0029] Figure 5 The effect of SPC concentration on W / O colostrum particle size, PDI and appearance. (a) Changes in particle size and PDI of W / O colostrum at different SPC concentrations, (b) Photographs of sample appearance.
[0030] Figure 6 The effects of SPC concentration on the particle size, PDI, and appearance of Ganoderma lucidum polysaccharide nanoliposomes are shown. (a) The changes in particle size and PDI of nanoliposomes at different SPC concentrations are shown, and (b) is a photograph of the sample appearance.
[0031] Figure 7 Encapsulation efficiency and morphology characterization of Ganoderma lucidum polysaccharide nanoliposomes were determined. (a) shows the effect of different sample volumes on encapsulation efficiency; (b) is a transmission electron microscope image of Ganoderma lucidum polysaccharide nanoliposomes prepared with an SPC concentration of 20 mg / mL. Detailed Implementation
[0032] The present invention will now be further described with reference to the accompanying drawings and embodiments.
[0033] Example 1
[0034] A method for preparing hydrophilic drug nanoliposomes based on microfluidic-low shear coupling multiple emulsion, comprising the following steps:
[0035] Preparation of Ganoderma lucidum polysaccharide solution: Accurately weigh the dried Ganoderma lucidum polysaccharide powder (Shaanxi Zhenghui Biotechnology Co., Ltd., purity 80%, molecular weight less than 100kDa), dissolve it in PBS buffer (pH 7.4) to prepare a 10mg / mL Ganoderma lucidum polysaccharide stock solution, and store it at 4℃ protected from light for later use.
[0036] Preparation of soybean lecithin (SPC) chloroform solution: Weigh SPC according to the experimental design concentration, dissolve it in chloroform and make up to the corresponding volume, with concentrations of 10 mg / mL, 20 mg / mL, 30 mg / mL, 40 mg / mL, 50 mg / mL, 60 mg / mL, 80 mg / mL and 100 mg / mL.
[0037] A 3D printer was used to print the chamber mold. Polydimethylsiloxane (PDMS) and curing agent were thoroughly mixed at a 10:1 mass ratio. The PDMS mixture was poured into the mold and baked at 45°C for 2 hours. Demolding yielded a cylindrical chamber with a diameter of 1.7 cm, as shown in the figure. A microtube was inserted into the lower part of the chamber and sealed with liquid PDMS and baked to ensure a leak-proof interface. The diameter of the microtube was 200 μm. A 1 mL syringe was used to draw up an aqueous solution of Ganoderma lucidum polysaccharide, which was fixed to a microinjection pump and connected to the chamber microtube through a needle. The entire chamber was then fixed on a homogenized stirring platform, completing the construction of the microfluidic-low-shear coupled nanoliposome preparation platform.
[0038] The two-step emulsification process consists of two stages. The first step is to prepare the W / O colostrum: 3 mL of SPC chloroform solution is added to the chamber as the oil phase. The stirrer is turned on and the speed is set (1000-10000 rpm). After the speed stabilizes, the syringe pump is turned on and the Ganoderma lucidum polysaccharide solution is injected into the oil phase in a micron-sized jet form through a 200 μm diameter microtube in a low-shear stirring field at a set flow rate (0.1-1.0 μL / s). The injection volume is 50 μL (for optimization experiments) or 100 μL (for encapsulation efficiency determination studies). After the injection is completed, the stirrer is turned off and the W / O colostrum sample is collected.
[0039] The second step is to prepare W / O / W double emulsions: The W / O promulgated emulsion collected in the first step is used as the dispersed phase and injected into the external aqueous phase (PBS buffer solution, pH 7.4) in the same way. After low-shear emulsification, W / O / W double emulsions are formed. Finally, chloroform is removed by rotary evaporation (100 Pa for 30 min, 75 Pa for 30 min, 50 Pa for 30 min) to obtain Ganoderma lucidum polysaccharide nanoliposomes.
[0040] This invention relates to the determination of particle size and dispersibility.
[0041] Colostrum particle size was determined by diluting the sample with chloroform in glass cuvettes and measuring the average particle size and polydispersity index (PDI) using a Zetasizer Lab nanoparticle size analyzer. Each sample was measured three times and the average value was taken. The particle size and dispersibility of nanoliposomes were measured using PBS dilution.
[0042] 1. Effect of flow rate on W / O colostrum particle size and PDI
[0043] Following the steps outlined above, the SPC concentration was first determined to be 20 mg / mL, the first-stage emulsification speed was 3000 rpm, and the microjets were set to flow rates of 0.1 μL / s, 0.2 μL / s, 0.3 μL / s, 0.4 μL / s, 0.5 μL / s, 0.6 μL / s, 0.7 μL / s, 0.8 μL / s, 0.9 μL / s, and 1.0 μL / s for the experiments.
[0044] The results are as follows Figure 2 As shown, the particle size remains less than 200 nm over a wide flow rate range (0.1-1 μL / s). This reflects the effectiveness of this method in preparing uniform nanoparticles. Within the 0.1-1 μL / s range, the initial emulsion particle size is not significantly dependent on the injection rate, but there is an optimal PDI range (0.2-0.5 μL / s), where the PDI is less than 0.2. Microjets that are too weak or too strong are detrimental to the formation of uniform nanoparticles. Considering particle size and dispersibility, an injection rate controlled at 0.2-0.5 μL / s is preferred for further research. Figure 2 Figure b shows a photograph of the corresponding sample. As can be seen in the figure, within the range of 0.2-0.5 μL / s, the initial emulsion is a uniform milky white, indicating good emulsification. The second stage continues with the same flow rate.
[0045] 2. Effect of rotational speed on W / O primary emulsion particle size and PDI
[0046] With a fixed SPC concentration of 20 mg / mL and a first injection flow rate of 0.2 μL / sec, stirring speeds were set at 1000 rpm, 2000 rpm, 3000 rpm, 4000 rpm, 5000 rpm, 6000 rpm, 7000 rpm, 8000 rpm, 9000 rpm, and 10000 rpm.
[0047] Experimental results are as follows Figure 3 As shown, similar to the injection rate, the initial emulsion particle size remained less than 200 nm within the 1000-10000 rpm range. The PDI (particulate density) tended to decrease with increasing rotational speed, stabilizing above 3000 rpm. Therefore, we selected 3000 rpm for subsequent research. Figure 3 Figure b shows some actual images of the samples. As can be seen from the figure, the milky white color of the samples becomes more obvious as the rotation speed increases, indicating that the emulsification effect improves with the increase of rotation speed.
[0048] 3. Effect of rotational speed on nanoliposome particle size and PDI
[0049] In the second emulsification process, the stirring speed, as a core parameter controlling the shear strength of the system and determining the dispersion behavior of the W / O / W double emulsion, directly affects the particle size, uniformity, and bilayer structure stability of the double emulsion. In this experiment, under the conditions of a fixed SPC concentration of 20 mg / mL and a first injection flow rate of 0.3 μL / s, the stirring speed gradient for the second emulsion was set to 3000, 5000, 7000, and 10000 rpm. The results are as follows: Figure 4 As shown.
[0050] Unlike the colostrum, where the particle size is not significantly dependent on rotational speed, the particle size of the nanoliposomes after rotary evaporation decreases with increasing rotational speed, but remains generally between 200-300 nm. Conversely, unlike the nanoliposome particle size, the PDI (particulate density index) initially decreases and then increases with increasing rotational speed. This indicates that both excessively high and low rotational speeds are detrimental to the formation of uniform liposomes. A possible reason is that lower rotational speeds cannot provide sufficient shear force to promote the formation of uniform nanoliposomes; while higher rotational speeds create turbulence, which is also unfavorable for uniform liposome formation. Overall, 5000-7000 rpm is the optimal range for the second emulsification rotational speed.
[0051] 4. Effect of SPC concentration on W / O colostrum particle size and PDI
[0052] The first-stage emulsification injection flow rate was fixed at 0.2 μL / sec, and the first-stage stirring speed was 3000 rpm. The SPC concentrations were set to be 10 mg / mL, 20 mg / mL, 30 mg / mL, 40 mg / mL, 50 mg / mL, 60 mg / mL, 80 mg / mL, and 100 mg / mL, respectively.
[0053] The results are as follows Figure 5 As shown, SPC concentration directly affects the viscosity of the oil phase and the stability of the interfacial film, thus affecting the emulsification effect of the primary emulsion. Under a fixed stirring speed of 3000 rpm, the particle size of the primary emulsion did not show a significant dependence on SPC concentration, but the PDI of the primary emulsion showed a trend of first decreasing and then increasing. Figure 5 Figure b shows some sample images. As can be seen from the figure, the colostrum gradually changes from milky white to yellow as the SPC concentration increases. In summary, 20-40 mg / mL is the optimal SPC concentration range for preparing colostrum.
[0054] 5. Effect of SPC concentration on particle size and PDI of nanoliposomes
[0055] The injection rate was fixed at 0.2 μL / s for two injections, and the rotation speed was fixed at 3000 rpm and 7000 rpm for two injections, respectively. The effect of SPC concentration on the second emulsification was investigated. Figure 6 As shown, the SPC concentration within the investigated range has a limited effect on the final particle size of the formed nanoliposomes; however, it has a significant effect on the PDI, showing a trend of first decreasing and then increasing. Based on the trend of PDI variation, the optimal SPC concentration range is 20-40 mg / mL, at which point the PDI is around 0.2. (From the actual appearance image...) Figure 6 (b) No significant difference was observed. In summary, the SPC concentration had a consistent effect on the emulsification results in both studies, with the optimal concentration range being 20-40 mg / mL.
[0056] 6. Encapsulation efficiency determination
[0057] The encapsulation efficiency of Ganoderma lucidum polysaccharide nanoliposomes was determined using an ultrafiltration-centrifugation-phenol-sulfuric acid-enzyme-labeled immunosorbent assay (ELISA). The specific steps are as follows:
[0058] (1) Isolation of free Ganoderma lucidum polysaccharides
[0059] Take two 1 mL ultrafiltration centrifuge tubes (molecular weight cutoff 100 kDa), add 500 μL of Ganoderma lucidum polysaccharide nanoliposome suspension to each, and centrifuge at 10,000 rpm for 5 min. Add an appropriate amount of ultrapure water to the inner tubes and wash, then centrifuge again at 10,000 rpm for 5 min. Repeat the washing 3-5 times to ensure that the free Ganoderma lucidum polysaccharide is completely filtered into the lower supernatant. Collect all the lower supernatant and dilute to 2 mL with ultrapure water as the test solution for free polysaccharide.
[0060] (2) Determination of total Ganoderma lucidum polysaccharides
[0061] Take 1 mL of untreated Ganoderma lucidum polysaccharide nanoliposome sample, add 1 mL of 1% Triton X-100 solution, mix thoroughly, and place in a constant temperature water bath for 60 min to shake and break the emulsion, so that the liposomes are completely broken and the encapsulated Ganoderma lucidum polysaccharide is released.
[0062] (3) Color development and detection
[0063] Take the above-mentioned free polysaccharide test solution and the total sample solution after demulsification, respectively, and perform color development using the phenol-sulfuric acid method: add 5% phenol solution and concentrated sulfuric acid sequentially, vortex to mix, and incubate at 45℃ for 1 hour. After cooling, add 335 μL of each to a 96-well plate, and measure the absorbance at 490 nm using a microplate reader. Each group is set up in triplicate.
[0064] Encapsulation rate calculation
[0065] Encapsulation ratio calculation formula:
[0066] Encapsulation efficiency (EE)% = (total A − free A) / total A × 100%, where A represents the absorbance of the sample.
[0067] To ensure a complete reaction of Ganoderma lucidum polysaccharides and improve detection accuracy, different volumes (200, 400, 600, and 800 μL) of samples were taken from the filtrate and demulsifier for a sulfuric acid-phenol colorimetric experiment. The results are as follows: Figure 7 As shown, the calculated encapsulation efficiency increases with increasing processing volume, reaching a stable level (~70%) above 400 μL. Compared to Ganoderma lucidum polysaccharide nanoliposomes prepared by the traditional thin-film hydration method (encapsulation efficiency of approximately 30%), the nanoliposomes prepared by the microfluidic-low-shear coupling two-step emulsification method used in this study achieved an encapsulation efficiency that was more than twice as high.
[0068] In summary, the microjets-low shear coupling strategy of this invention effectively reduces the energy threshold required for nanoemulsification. Unlike traditional high-shear homogenization methods that require speeds above 20,000 rpm, this method utilizes a 200 μm diameter microtube to inject the internal aqueous phase into the oil phase as a micron-sized jet. The large specific surface area of the microjets allows for efficient fragmentation into nano-sized droplets at low speeds of 3,000-7,000 rpm, achieving low-damage encapsulation of Ganoderma lucidum polysaccharides. The initial injection flow rate has a limited effect on the promulgated particle size but a significant impact on dispersibility. Within a wide range of 0.1-1.0 μL / s, the promulgated particle size remains consistently less than 200 nm, but the PDI is optimal in the 0.2-0.5 μL / s range (<0.2), indicating that suitable microjets are crucial for obtaining uniform nanoparticles. The initial stirring speed and SPC concentration have a synergistic regulatory effect on product performance. The PDI (Potential Intensity Dissolved) decreased steadily during the first emulsification at speeds above 3000 rpm; the PDI of the nanoliposomes was lowest during the second emulsification at speeds between 5000-7000 rpm; and the PDI was optimal for both emulsifications when the SPC concentration was between 20-40 mg / mL. Encapsulation efficiency was significantly improved. Using ultrafiltration-centrifugation-phenol-sulfuric acid-enzyme-labeled immunosorbent assay (ELISA), the encapsulation efficiency of Ganoderma lucidum polysaccharide nanoliposomes under the optimized process reached over 70%, more than twice that of the traditional thin-film hydration method (approximately 30%), validating the effectiveness of the microfluidic-low-shear coupled double emulsification method for the efficient encapsulation of large molecular weight water-soluble drugs.
[0069] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.
Claims
1. A method for preparing hydrophilic drug nanoliposomes based on a microfluidic-low shear coupling double emulsion method, characterized by, Prepared according to the following method: (1) respectively prepare a hydrophilic drug aqueous solution and a soybean lecithin chloroform solution; (2) add the soybean lecithin chloroform solution as the oil phase in the chamber, and distribute microtubes in the lower part of the chamber; under low-speed stirring shear, inject the hydrophilic drug aqueous solution through the microtubes in the form of micron-level jet into the oil phase in the low shear stirring field; after injection, turn off the stirring, and collect the W / O initial milk sample; (3) use the W / O initial milk sample as the dispersed phase, and inject it into the external aqueous phase in the same way as in step (2), and form a W / O / W multiple emulsion through secondary low-speed stirring shear; (4) remove chloroform from the W / O / W multiple emulsion by evaporation under reduced pressure to obtain hydrophilic drug nanoliposomes.
2. The method for preparing hydrophilic drug nanoliposomes based on the microfluidic-low shear coupling double emulsion method according to claim 1, characterized in that: The hydrophilic drug is ganoderma polysaccharide.
3. The method for preparing hydrophilic drug nanoliposomes based on the microfluidic-low shear coupling double emulsion method according to claim 2, characterized in that, In step (1), the operation of preparing the hydrophilic drug aqueous solution is as follows: accurately weigh the ganoderma polysaccharide powder with a molecular weight less than 100 kDa dried to a constant weight, dissolve it with PBS buffer, prepare a 10 mg / mL ganoderma polysaccharide solution, and store it at 4°C away from light for standby use; the concentration of the soybean lecithin chloroform solution is 10-100 mg / mL.
4. The method for preparing hydrophilic drug nanoliposomes based on the microfluidic-low shear coupling double emulsion method according to claim 3, characterized in that: The concentration of the soybean lecithin chloroform solution is 20-40 mg / mL.
5. The method for preparing hydrophilic drug nanoliposomes based on the microfluidic-low shear coupling double emulsion method according to any one of claims 1-4, characterized in that: In step (2), the tube diameter of the microtube is 100-300 μm, the stirring shear speed is 1000-10000 rpm, the hydrophilic drug aqueous solution is injected by a syringe pump, and the flow rate of the syringe pump is 0.1-1.0 uL / s.
6. The method for preparing hydrophilic drug nanoliposomes based on the microfluidic-low shear coupling double emulsion method according to claim 5, characterized in that: In step (2), the shear stirring speed is 3000 rpm, and the flow rate of the syringe pump is 0.2-0.5 uL / s.
7. The method for preparing hydrophilic drug nanoliposomes based on the microfluidic-low shear coupling double emulsion method according to claim 6, characterized in that: In step (3), the external aqueous phase is PBS buffer, and the secondary low-speed stirring shear speed is 3000-10000 rpm.
8. The method for preparing hydrophilic drug nanoliposomes based on the microfluidic-low shear coupling double emulsion method according to claim 7, characterized in that: The secondary low-speed stirring shear speed is 5000-7000 rpm.
9. The method for preparing hydrophilic drug nanoliposomes based on the microfluidic-low shear coupling double emulsion method according to claim 8, characterized in that: In step (4), the gradient reduced pressure evaporation is used, and the absolute pressure is 100 Pa, 75 Pa, and 50 Pa, respectively, for 30 minutes of rotary evaporation.
10. Hydrophilic drug nanoliposomes prepared by the method of claim 1-9.