Disc-shaped nano-liposome carrying insoluble drug, and preparation method and application thereof

Abstract

The invention relates to a discoid nano-liposome carrying an insoluble drug, and a preparation method and application thereof. The invention belongs to the technical field of medicines, and provides a disc-shaped nano-liposome as well as a preparation method and application thereof. Cholesterol, 1-palmitoyl-2-oleoyl-lecithin, distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and (2, 3-dioleoyl-propyl)-trimethyl ammonium chloride are used as main materials, one or more insoluble drugs can be entrapped, and the drug carrier is suitable for treatment of cancer diseases and kidney diseases. The discoid nano-liposome can significantly improve the solubility of the drug and meet the purpose of passive targeting. In addition, the disc-shaped nano-liposome is high in stability, can effectively improve the bioavailability of the medicine and increase the safety of the medicine, and has a wide clinical application prospect.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and particularly relates to a method for preparing a discoid nanoliposome carrying a poorly soluble drug and its application in cancer diseases and kidney diseases. Background Art

[0002] Improving the solubility of poorly soluble drugs is a difficult and hot topic in the field of pharmacy. At present, the main methods to improve drug solubility are: 1. Making water-soluble prodrugs: The drug is modified into an ester or the molecular structure is modified to form a prodrug that is covalently bound to a hydrophilic macromolecule, thereby increasing the water solubility of the poorly soluble drug. 2. Making salts: Some poorly soluble weak acid or weak base drugs can be formed into soluble salts by adding acid or base to adjust the pH value of the drug solution. 3. Adding solubilizers, cosolvents or miscible solvents. 4. Making new preparations such as inclusion compounds, solid dispersions or liposomes.

[0003] Discoidal liposomes are an emerging nano drug delivery system, which are composed of phospholipid materials and skeleton materials, have a double-layer phospholipid membrane structure, and can be used as a carrier for poorly soluble drugs. Unlike traditional spherical nanoliposomes, discoidal nanoliposomes are in the shape of oblate discs, and have the following advantages in drug delivery: 1. High aspect ratio: discoidal nanoliposomes have the same high aspect ratio (high permeability) as rod-shaped nanoliposomes, and their overall shape is similar to spherical nanoliposomes (high retention), so discoidal nanoliposomes are expected to improve the targeting and penetration ability of drugs, thereby achieving the purpose of increasing the therapeutic effect of drugs; 2. Vascular wall tropism: The blood flow in the blood vessels is laminar, and there is a certain shear rate, which will pull the liposomes in the blood vessels back to the blood flow from close to the blood vessel wall. Compared with traditional spherical nanoliposomes, discoid nanoliposomes with high aspect ratio are more inclined to adhere to the surface of the blood vessel wall, thereby penetrating the blood vessel wall to reach the lesion site; 3. Bionics advantage: The appearance of discoid nanoliposomes is similar to red blood cells and platelets in the blood, which has certain bionic advantages and can effectively avoid being recognized by the reticuloendothelial system; and from the perspective of contact angle, only when the discoid nanoliposomes are rotated to a certain angle so that the long axis of the discoid nanoliposomes falls on the surface of the cell membrane, will they be engulfed by macrophages. Therefore, compared with spherical nanoliposomes, discoid nanoliposomes can effectively prolong the circulation time of liposomes in the blood and improve the bioavailability of drugs.

[0004] Solid tumor tissues are rich in blood vessels. Compared with normal tissues, the gaps between blood vessel walls are wider, the structural integrity is poor, and lymphatic return is absent. Discoid nanoliposomes have a high aspect ratio and can selectively penetrate and remain in tumor tissues. Similarly, in kidney tissues, due to the mechanical barrier of the glomerular filtration membrane, only particles with a particle size of less than 20nm can be filtered by the glomerulus. The short diameter of the discoid nanoliposomes in the present invention is about 10 to 15nm. Under the action of blood laminar flow, the short axis of the discoid nanoliposomes can be aligned with the pores of the glomerular filtration membrane, pass vertically and reach the renal tubules, thereby achieving the purpose of targeted therapy.

[0005] In summary, the discoid nanoliposomes described in the present invention have good targeting properties, can effectively improve the solubility of poorly soluble drugs, and are expected to provide a new strategy for the treatment of tumor diseases and kidney diseases, which is of great significance. Summary of the invention

[0006] One of the purposes of the present invention is to address the deficiencies in the prior art and to provide a method for preparing discoid nanoliposomes carrying poorly soluble drugs and their application in cancer and kidney diseases.

[0007] Studies have shown that when the molar ratio of the PEG component in the excipient is controlled at 10% to 25%, a disc-shaped nanoliposome structure can be formed. The present invention successfully prepares disc-shaped nanoliposomes with a particle size of 60 to 120 nm by controlling the molar content of the PEG component. The inventors have found that the disc-shaped nanoliposomes can encapsulate one or more poorly soluble drugs and have good stability, and have broad clinical application prospects.

[0008] One of the purposes of the present invention is to provide a disc-shaped nanoliposome carrying a poorly soluble drug, which comprises, based on weight, 1 part of the poorly soluble drug, 1 to 10 parts of cholesterol, 1 to 10 parts of 1-palmitoyl-2-oleoyl-phosphatidylcholine, 1 to 100 parts of distearoyl phosphatidylethanolamine-polyethylene glycol 2000, and 1 to 10 parts of (2,3-dioleoyl-propyl)-trimethylammonium chloride; preferably, 1 part of the poorly soluble drug, 1 to 5 parts of cholesterol, 1 to 5 parts of 1-palmitoyl-2-oleoyl-phosphatidylcholine, 1 to 50 parts of distearoyl phosphatidylethanolamine-polyethylene glycol 2000, and 1 to 5 parts of (2,3-dioleoyl-propyl)-trimethylammonium chloride.

[0009] The poorly soluble drug of the present invention is selected from one or more of silybin, triptolide, triptolide, acetaminophen, salbutamol, doxorubicin, dexamethasone, curcumin, resveratrol, honokiol, pirarubicin or teniposide.

[0010] The preparation of the present invention further contains other excipients or pharmaceutically acceptable preparations, wherein the excipients are selected from one or more of isotonicity regulators, antioxidants, preservatives, and pH regulators.

[0011] One of the purposes of the present invention is to provide a method for preparing discoidal nanoliposomes carrying poorly soluble drugs, characterized in that the method comprises the following steps:

[0012] A. Preparation of lipid solution: Dissolve poorly soluble drugs, cholesterol, 1-palmitoyl-2-oleoyl-phosphatidylcholine, distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and (2,3-dioleoyl-propyl)-trimethylammonium chloride in an organic solvent according to a certain mass ratio to obtain a lipid solution.

[0013] B. removing the organic solvent from the lipid solution by concentrating under reduced pressure using a rotary evaporator to obtain a lipid film;

[0014] C. adding a hydration solvent to the lipid film to obtain a lipid hydration solution;

[0015] D. Probe ultrasound or high-pressure homogenization is performed on the lipid hydration liquid to obtain disc-shaped nanoliposomes. The particle size of the disc-shaped nanoliposomes is 60 to 120 nm.

[0016] The organic solvent in step A is selected from a mixture of one or more of methanol, acetonitrile, chloroform, anhydrous ethanol, dichloromethane, and acetone, preferably chloroform; in step B, the temperature for reduced pressure concentration is 30 to 60° C., preferably 45° C.; and the hydration solvent in step C is selected from purified water, 0.9% saline, and 5% glucose solution.

[0017] One of the purposes of the present invention is to provide a discoidal nanoliposome loaded with poorly soluble drugs for use in preparing drugs for treating cancer and kidney diseases.

[0018] The cancer diseases include breast cancer, lung cancer, intestinal cancer, gastric cancer, thyroid cancer, prostate cancer, liver cancer, esophageal cancer and intestinal cancer. The kidney diseases include acute glomerulonephritis, chronic glomerulonephritis, nephrotic syndrome, IgA nephropathy, tubulointerstitial nephritis, renal tubular acidosis and tubulointerstitial fibrosis.

[0019] The present invention has the following advantages:

[0020] (1) The discoid nanoliposomes of the present invention have high drug loading capacity and good stability;

[0021] (2) The discoid nanoliposomes of the present invention have a certain sustained release effect;

[0022] (3) The discoid nanoliposomes of the present invention have a higher aspect ratio and have the advantages of both the high permeability of nanorods and the high retention of nanospheres. Compared with spherical nanoliposomes, they have stronger penetration ability and passive targeting.

[0023] (4) The discoid nanoliposomes of the present invention have tropism for the blood vessel wall and can efficiently penetrate the blood vessel wall to reach the lesion site;

[0024] (5) The discoid nanoliposomes of the present invention have an appearance similar to red blood cells and platelets in the blood, and have certain biomimetic advantages. They can effectively prolong the circulation time of liposomes in the blood and improve the bioavailability of drugs.

[0025] (6) The preparation method of the discoid nanoliposomes of the present invention is simple and suitable for large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The embodiments of the present invention are described in detail below with reference to the accompanying drawings, wherein:

[0027] Figure 1 This is a transmission electron micrograph of the discoid nanoliposomes in Example 2.

[0028] Figure 2 These are the in vitro stability test results of the discoid nanoliposomes in Example 2.

[0029] A is the in vitro stability test result of the discoid nanoliposomes in Example 2 at 4°C.

[0030] B is the in vitro stability test result of the discoid nanoliposomes in Example 2 at room temperature.

[0031] Figure 3 These are the in vitro release experimental results of the discoid nanoliposomes in Example 2.

[0032] Figure 4 Pharmacokinetic results of DiD-labeled discoid nanoliposomes.

[0033] Figure 5 The in vivo distribution results of DiD-labeled discoid nanoliposomes.

[0034] Figure 6 These are the pharmacodynamic evaluation results of the discoid nanoliposomes against tubulointerstitial fibrosis in Example 2.

[0035] A shows the changes in kidney appearance of mice in each group after drug administration.

[0036] B shows the changes in kidney weight of mice in each group after administration.

[0037] Figure 7This is the safety evaluation result of the discoid nanoliposomes in Example 2. DETAILED DESCRIPTION

[0038] The following examples are further explanations of the present invention, but are by no means limitations of the scope of the present invention. The present invention will be further described in detail below with reference to the examples, but it should be understood by those skilled in the art that the present invention is not limited to these examples and the preparation methods used. Moreover, those skilled in the art may carry out equivalent substitutions, combinations, improvements or modifications to the present invention based on the description of the present invention, but these will all be included within the scope of the present invention.

[0039] Example 1

[0040] 5 mg of silybin, 5 mg of cholesterol, 10 mg of 1-palmitoyl-2-oleoyl phosphatidylcholine, 50 mg of distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and 5 mg of (2,3-dioleoyl-propyl)-trimethylammonium chloride were dissolved in methanol and rotary evaporated in a 30°C water bath to form a film. A certain volume of purified water was added for hydration and probe sonication was performed to obtain disc-shaped nanoliposomes loaded with silybin with a particle size of 62 nm. They were injected intravenously for targeted treatment of breast cancer.

[0041] Example 2

[0042] 5 mg of celastrol, 15 mg of cholesterol, 20 mg of 1-palmitoyl-2-oleoyl phosphatidylcholine, 50 mg of distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and 15 mg of (2,3-dioleoyl-propyl)-trimethylammonium chloride were dissolved in chloroform, and the mixture was rotary evaporated in a 50°C water bath to form a film. A certain volume of 0.9% saline was added for hydration, and disc-shaped nanoliposomes loaded with celastrol were obtained after high-pressure homogenization. The particle size was 98 nm, and the liposomes were intravenously injected for the targeted treatment of tubular interstitial fibrosis.

[0043] Example 3

[0044] 5 mg of curcumin, 25 mg of cholesterol, 30 mg of 1-palmitoyl-2-oleoyl phosphatidylcholine, 100 mg of distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and 10 mg of (2,3-dioleoyl-propyl)-trimethylammonium chloride were dissolved in acetonitrile and rotary evaporated in a 60°C water bath to form a film. A certain volume of 5% glucose solution was added for hydration. After probe ultrasound, disc-shaped nanoliposomes loaded with curcumin were obtained with a particle size of 102 nm. They were injected intravenously for targeted treatment of lung cancer.

[0045] Example 4

[0046] 5 mg of doxorubicin, 30 mg of cholesterol, 50 mg of 1-palmitoyl-2-oleoyl phosphatidylcholine, 200 mg of distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and 5 mg of (2,3-dioleoyl-propyl)-trimethylammonium chloride were dissolved in anhydrous ethanol and rotary evaporated in a water bath at 30°C to form a film. A certain volume of purified water was added for hydration and probe sonication was performed to obtain disc-shaped nanoliposomes loaded with silybin with a particle size of 114 nm. They were injected intravenously for targeted treatment of gastric cancer.

[0047] Example 5

[0048] 5 mg of honokiol, 50 mg of cholesterol, 50 mg of 1-palmitoyl-2-oleoyl phosphatidylcholine, 250 mg of distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and 5 mg of (2,3-dioleoyl-propyl)-trimethylammonium chloride were dissolved in a mixed solvent of methanol and acetone, and the mixture was rotary evaporated in a water bath at 30°C to form a film. A certain volume of purified water was added for hydration, and after probe sonication, disc-shaped nanoliposomes loaded with silybin were obtained with a particle size of 115 nm, which were injected intravenously for targeted treatment of prostate cancer.

[0049] Example 6

[0050] 3 mg of resveratrol, 3 mg of doxorubicin, 25 mg of cholesterol, 50 mg of 1-palmitoyl-2-oleoyl phosphatidylcholine, 150 mg of distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and 10 mg of (2,3-dioleoyl-propyl)-trimethylammonium chloride were dissolved in dichloromethane and rotary evaporated in a 45°C water bath to form a film. A certain volume of 5% glucose solution was added for hydration. After probe ultrasound, disc-shaped nanoliposomes carrying silybin and tripterygium wilfordii were obtained with a particle size of 106 nm. They were injected intravenously for the targeted treatment of tubulointerstitial nephritis.

[0051] Example 7

[0052] 3 mg of curcumin, 3 mg of honokiol, 40 mg of cholesterol, 50 mg of 1-palmitoyl-2-oleoyl phosphatidylcholine, 200 mg of distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and 10 mg of (2,3-dioleoyl-propyl)-trimethylammonium chloride were dissolved in chloroform and rotary evaporated in a 45°C water bath to form a film. A certain volume of 5% glucose solution was added for hydration, and after probe ultrasound, disc-shaped nanoliposomes loaded with silybin and tripterygium wilfordii were obtained with a particle size of 110 nm. They were injected intravenously for targeted treatment of nephrotic syndrome.

[0053] Example 8

[0054] 3 mg of celastrol, 3 mg of curcumin, 50 mg of cholesterol, 50 mg of 1-palmitoyl-2-oleoyl phosphatidylcholine, 350 mg of distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and 15 mg of (2,3-dioleoyl-propyl)-trimethylammonium chloride were dissolved in anhydrous ethanol and rotary evaporated in a 45°C water bath to form a film. A certain volume of 5% glucose solution was added for hydration, and after probe ultrasound, disc-shaped nanoliposomes carrying silybin and celastrol were obtained with a particle size of 119 nm. They were injected intravenously for targeted treatment of lung cancer.

[0055] Experimental Example 1: Morphological Investigation of Drug-Loaded Discoid Nanoliposomes

[0056] Take an appropriate amount of the discoid nanoliposomes loaded with tripterygium wilfordii in Example 2, dilute with PBS solution to a suitable lipid concentration, then add 2% phosphotungstic acid for staining, and observe the morphology and size of the discoid nanoliposomes under a transmission electron microscope.

[0057] Figure 1 The transmission electron micrograph of tripterygium wilfordii discoid nanoliposomes. The results show that the electron micrograph of tripterygium wilfordii discoid nanoliposomes has two shapes: round and rod-shaped. It is speculated that they are the cross-section (round) and longitudinal section (rod-shaped) of the discoid nanoliposomes, respectively, indicating the successful preparation of the liposomes.

[0058] Experimental Example 2: Stability Study of Drug-Loaded Discoid Nanoliposomes

[0059] The present invention selected the discoid nanoliposomes loaded with tripterygium wilfordii in Example 2 as a model to study the stability of the preparation. The prepared discoid nanoliposomes were stored at 4°C and room temperature, and samples were taken at regular intervals to measure the particle size and record the change in particle size.

[0060] The stability results of drug-loaded discoid liposomes are shown in Figure 2 -A and Figure 2 It can be seen that under 4°C and room temperature conditions, the particle size and PDI of the discoid nanoliposomes did not change significantly within 14 days, and there was no drug precipitation, showing good stability.

[0061] Experimental Example 3: In vitro release study of drug-loaded discoid nanoliposomes

[0062] An appropriate amount of the discoid nanoliposomes loaded with tripterygium wilfordii prepared in Example 2 was placed in a dialysis bag with a molecular cutoff of 8000Da. The dialysis bag was then placed in 50mL of PBS solution containing 0.2% Tween 80, and shaken at a constant speed (100rpm) in a shaker at 37°C. Samples were taken at pre-set time points, and the content of tripterygium wilfordii in the release medium was determined by HPLC to calculate the cumulative release amount.

[0063] Figure 3The results of the in vitro release experiment of the discoid nanoliposomes loaded with tripterygium wilfordii in Example 2 show that the discoid nanoliposome group has a better sustained release effect in vitro than the tripterygium wilfordii original drug solution group, indicating that the liposomes of the present invention can be used for sustained release of drugs.

[0064] Experimental Example 4: Pharmacokinetic Study of Discoid Nanoliposomes

[0065] The discoid nanoliposomes were labeled with the lipophilic fluorescent dye DiD. DiD was added to an organic solvent together with a lipid material. The preparation method was similar to that in Example 2, specifically, 0.5 mg DiD, 15 mg cholesterol, 20 mg 1-palmitoyl-2-oleoyl phosphatidylcholine, 50 mg distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and 15 mg (2,3-dioleoyl-propyl)-trimethylammonium chloride were dissolved in acetonitrile, and the film was formed by rotary evaporation in a 50°C water bath. A certain volume of 0.9% physiological saline was added for hydration, and the discoid nanoliposomes loaded with DiD were obtained after high-pressure homogenization.

[0066] Healthy male SD rats were randomly divided into 3 groups, 6 rats in each group. DiD original drug and DiD-loaded discoid nanoliposomes were injected through the tail vein (the dosage was 200 μg / kg, calculated according to DiD). 300 μL of blood was collected from the orbit at 5, 15, 30 minutes and 1, 2, 4, 8, 12, 24, 36, 48, and 72 hours after administration, respectively, and placed in an EP tube containing 1% sodium heparin, and centrifuged at 6000 rpm for 5 minutes. 100 μL of supernatant was taken, 300 μL of methanol was added to precipitate protein, and after centrifugation at 13000 rpm for 10 minutes, the supernatant was taken, and the fluorescence intensity of DiD in plasma at each time point was measured using an enzyme marker.

[0067] Figure 4 The pharmacokinetic results of the discoid nanoliposomes loaded with DiD show that the fluorescence intensity of DiD in the plasma of rats in the discoid nanoliposome group is significantly stronger than that in the DiD original drug group, proving that the discoid nanoliposomes in the present invention can significantly prolong the circulation time of the drug in the body and improve the bioavailability of the drug.

[0068] Experimental Example 5: In vivo distribution study of discoid nanoliposomes

[0069] DiD-loaded discoid nanoliposomes were prepared according to the method described in Experimental Example 4. Mice with successful tubulointerstitial fibrosis modeling were randomly divided into two groups on the 10th day after modeling: a DiD original drug group and a DiD-loaded discoid nanoliposome group, with 3 mice in each group. After DiD original drug and DiD-loaded discoid nanoliposomes were injected through the tail vein (the dosage was 200 μg / kg, calculated according to DiD), the mice were killed at the 4h time point, the kidney tissue was removed, and the fluorescence intensity of the kidney tissue was semi-quantified using a live imaging device.

[0070] Figure 5 The results are the in vivo distribution results of the DiD-loaded discoid nanoliposomes. The results show that the fluorescence intensity of the DiD-loaded discoid nanoliposome group in the kidney of mice is significantly stronger than that of the DiD original drug group, proving that the liposomes of the present invention can be used as carriers for drug targeted therapy.

[0071] Experimental Example 6: Pharmacodynamic evaluation of drug-loaded discoid nanoliposomes

[0072] Fifteen mice with successful tubulointerstitial fibrosis modeling were randomly divided into three groups: saline group, tripterygium wilfordii original drug group, and tripterygium wilfordii discoid nanoliposome group. Healthy mice were taken as controls. The drug was administered on the third day after modeling, with a dose of 1 mg / kg, once every other day, for a total of 5 times. The mice were killed 24 hours after the last administration, and the kidneys were removed for observation and weighing.

[0073] The experimental results are as follows Figure 6 -A and Figure 6 -B shows that the kidney tissues of mice in the saline group and the original drug group of tripterygium wilfordii showed obvious swelling and effusion, the color of the kidneys became lighter, lost luster, and the toughness became worse; the swelling degree of the group loaded with tripterygium wilfordii discoid nanoliposomes was significantly reduced. The weighing results also showed that the treatment results of the drug-loaded discoid nanoliposome group were significantly better than those of the original drug group. In summary, the discoid nanoliposomes significantly improved the anti-renal interstitial fibrosis efficacy of tripterygium wilfordii.

[0074] Experimental Example 7: Safety evaluation of drug-loaded discoid nanoliposomes

[0075] Healthy male SD rats were randomly divided into 3 groups, 5 rats in each group. Physiological saline, celastrol original drug solution (1 mg / kg), and celastrol-loaded discoid nanoliposomes (1 mg / kg) were injected through the tail vein, respectively, once every two days, for 5 consecutive times. The rats were killed 24 hours after the last administration, and the heart, liver, spleen, lung, kidney and other organs were removed, and then H&E staining was performed, and the changes in the tissues and organs of each group of rats were observed under a microscope.

[0076] The experimental results are as follows Figure 7 As shown. It can be seen that compared with the saline group, the slice results of the tripterygium wilfordii original drug group showed cardiotoxicity and hepatotoxicity, which were specifically manifested as thinning and dissolution of myocardial fibers, atrophy of hepatocytes, thinning of hepatic cords and other pathological changes. The toxicity of the discoid nanoliposome group loaded with tripterygium wilfordii to various organs was significantly reduced, and there was no significant difference with the saline group. In summary, the discoid nanoliposome loaded with tripterygium wilfordii can effectively reduce the toxicity of drugs to various tissues and organs.

Claims

1. A discoidal nanoliposome loaded with a poorly soluble drug, characterized in that: Contains: poorly soluble drugs, cholesterol, 1-palmitoyl-2-oleoyl-phosphatidylcholine, distearoylphosphatidylethanolamine-polyethylene glycol 2000 and (2,3-dioleoyl-propyl)-trimethylammonium chloride. Based on weight parts, it contains 1 part of poorly soluble drugs, 1 to 10 parts of cholesterol, 1 to 10 parts of 1-palmitoyl-2-oleoyl-phosphatidylcholine, 1 to 100 parts of distearoyl phosphatidylethanolamine-polyethylene glycol 2000, and 1 to 10 parts of (2,3-dioleoyl-propyl)-trimethylammonium chloride.

2. The discoidal nanoliposome loaded with poorly soluble drugs according to claim 1, characterized in that: The invention comprises 1 part of poorly soluble drugs, 1 to 5 parts of cholesterol, 1 to 5 parts of 1-palmitoyl-2-oleoyl-phosphatidylcholine, 1 to 50 parts of distearoyl phosphatidylethanolamine-polyethylene glycol 2000, and 1 to 5 parts of (2,3-dioleoyl-propyl)-trimethylammonium chloride.

3. The discoidal nanoliposome loaded with poorly soluble drugs according to claim 1, characterized in that: The poorly soluble drug is selected from one or more of silybin, triptolide, triptolide, acetaminophen, salbutamol, doxorubicin, dexamethasone, curcumin, resveratrol, honokiol, pirarubicin or teniposide.

4. The discoidal nanoliposome loaded with poorly soluble drugs according to claim 1, characterized in that: The preparation further contains other excipients or pharmaceutically acceptable preparations, wherein the excipients are selected from one or more of isotonicity regulators, antioxidants, preservatives, and pH regulators.

5. A method for preparing discoidal nanoliposomes loaded with poorly soluble drugs according to any one of claims 1 to 4, characterized in that: The steps include: A. preparing a lipid solution: dissolving cholesterol, 1-palmitoyl-2-oleoyl-phosphatidylcholine, distearoyl phosphatidylethanolamine-polyethylene glycol 2000, (2,3-dioleoyl-propyl)-trimethylammonium chloride and a poorly soluble drug in an organic solvent according to a certain mass ratio to obtain a lipid solution; B. removing the organic solvent from the lipid solution by concentrating under reduced pressure using a rotary evaporator to obtain a lipid film; C. adding a hydration solvent to the lipid film to obtain a lipid hydration solution; D. The lipid hydration liquid is subjected to probe ultrasonication or high-pressure homogenization to obtain disc-shaped nanoliposomes, wherein the particle size of the disc-shaped nanoliposomes is 60 to 120 nm.

6. The preparation method according to claim 5, characterized in that: The organic solvent in step A is selected from a mixture of one or more of methanol, acetonitrile, chloroform, anhydrous ethanol, dichloromethane, and acetone; in step B, the temperature for reduced pressure concentration is 30-60° C.; and the hydration solvent in step C is selected from purified water, 0.9% saline, or 5% glucose solution.

7. The preparation method according to claim 5, characterized in that: In the step A, the organic solvent is selected from chloroform.

8. The preparation method according to claim 5, characterized in that: In the step B, the temperature for concentration under reduced pressure is 45°C.

9. Use of the discoid nanoliposome loaded with a poorly soluble drug according to any one of claims 1 to 4 or the discoid nanoliposome loaded with a poorly soluble drug prepared by the preparation method according to any one of claims 5 to 9 in the preparation of drugs for treating cancer diseases and kidney diseases.

10. The use according to claim 9, characterized in that: The cancer diseases include breast cancer, lung cancer, colon cancer, stomach cancer, thyroid cancer, prostate cancer, liver cancer, esophageal cancer and colon cancer.

11. The use according to claim 9, characterized in that: The kidney diseases include acute glomerulonephritis, chronic glomerulonephritis, nephrotic syndrome, IgA nephropathy, tubulointerstitial nephritis, renal tubular acidosis and tubulointerstitial fibrosis.

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