Drug-loaded double-chamber liposome and preparation method and application thereof

Abstract

The present application relates to a drug-loaded double-chamber liposome, which comprises a double-chamber liposome and a drug loaded in the double-chamber liposome; the double-chamber liposome comprises a first liposome and a second liposome encapsulated in the first liposome, the first liposome and the second liposome have independent lipid bilayers, and the drug is loaded in the lipid bilayers of the independent first liposome and the second liposome; and the membrane material of the double-chamber liposome comprises phospholipid, cholesterol and essential oil molecules. By introducing essential oil molecules into lecithin, the essential oil molecules can be embedded in the lipid bilayer, the fluidity and microstructure of the phospholipid membrane bilayer are regulated, the bending and invagination of the lipid membrane are induced in the process of lipid membrane extrusion, and a unique liposome structure with a separated double-chamber in the interior is stably formed.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology and relates to a drug-loaded bicompartment liposome, its preparation method, and its application. Background Technology

[0002] Liposomes are hollow, closed vesicles composed of a phospholipid bilayer, capable of encapsulating hydrophilic or hydrophobic drugs. They possess advantages such as good biocompatibility and high modifiability, leading to their widespread application in drug delivery. Traditional liposomes are mostly single-chambered vesicles, meaning they contain only one hydrophilic cavity. In recent years, to improve the delivery efficiency of drug carriers and broaden their functionality, researchers have focused on developing more complex liposome structures, such as multilayered vesicles or vesicles with different internal structures. Among these, liposomes with two independent compartments offer new possibilities for controlling delivery mechanisms (such as controlling the release sequence). Theoretically, this structure can more effectively regulate drug release kinetics or achieve synergistic therapy. Existing methods for preparing complex liposome structures typically involve cumbersome steps, requiring the use of specific templates (such as reverse emulsions or microfluidic technology), complex phase modulation (such as multi-component systems), or special post-processing techniques. These methods often suffer from problems such as complex processes, poor reproducibility, high costs, or difficulty in large-scale production. Furthermore, obtaining liposomes with specific internal chambers stably through simple methods remains a technical challenge, especially in terms of precisely controlling the assembly behavior of the lipid membrane to form regular liposome structures.

[0003] Transdermal drug delivery, as a non-invasive method of drug administration, avoids the first-pass effect in the liver and gastrointestinal adverse reactions associated with oral administration, providing stable and sustained blood drug concentrations. However, due to the natural barrier effect of the stratum corneum, the transdermal absorption rate of most drugs is very low. Liposomes, as biocompatible carriers, can effectively fuse with lipids in the stratum corneum, promoting drug penetration. However, there is still room for improvement in the penetration-enhancing behavior of conventional single-compartment liposomes. Therefore, there is an urgent need to develop novel liposome carriers that are simple to prepare, low in cost, and can significantly improve the transdermal performance of drugs. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the present invention aims to provide a drug-loaded bicompartment liposome, its preparation method, and its application.

[0005] To achieve this objective, the present invention adopts the following technical solution: In a first aspect, the present invention provides a drug-loaded bicompartmental liposome, the drug-loaded bicompartmental liposome comprising a bicompartmental liposome and a drug loaded inside the bicompartmental liposome; the bicompartmental liposome comprises a first liposome and a second liposome encapsulated inside the first liposome, the first liposome and the second liposome having their own independent lipid bilayer, the drug being loaded inside the lipid bilayer of the respective independent first liposome and the second liposome; the membrane material of the bicompartmental liposome comprises phospholipids, cholesterol and essential oil molecules.

[0006] This invention creatively designs a drug-carrying bicompartment liposome. The liposome is prepared by introducing essential oil molecules into lecithin. These essential oil molecules can embed into the lipid bilayer, regulating the fluidity and microstructure of the phospholipid membrane. During lipid membrane extrusion, the membrane is induced to bend and indent, thereby stably forming a unique liposome structure with internally separated bicompartments. The prepared bicompartment liposomes are characterized by uniform particle size, adjustable membrane fluidity, and good biocompatibility. Compared with traditional single-compartment liposomes, the bicompartment liposomes provided by this invention exhibit superior transdermal delivery performance as drug carriers, particularly in promoting the skin penetration of hydrophobic drugs.

[0007] Preferably, the drug is embedded in the hydrophobic region of a lipid bilayer of a separate first liposome and a second liposome.

[0008] Preferably, the mass ratio of the phospholipids, cholesterol, and essential oil molecules is (5-15):(1-3):(1-5) (wherein, the specific values ​​of 5-15 can be 5, 6, 7, 9, 10, 12, 15, etc., the specific values ​​of 1-3 can be 1, 2, 3, etc., and the specific values ​​of 1-5 can be 1, 2, 3, 4, 5, etc.).

[0009] Preferably, the phospholipids include any one or a combination of at least two of soybean lecithin, hydrogenated lecithin, and egg yolk lecithin.

[0010] Preferably, the essential oil molecule is a monoterpenoid compound.

[0011] Preferably, the essential oil molecules include any one or a combination of at least two of linalool, geraniol, tetrahydrogeraniol, citronellol, citral, α-terpineol, 4-terpineol, menthol, camphor, and carvone.

[0012] Preferably, the drug is a lipid-soluble small molecule drug.

[0013] Preferably, the drug comprises any one or a combination of at least two of N,N,N',N'-tetra(2-pyridylmethyl)ethylenediamine, ruxotinib, quercetin, and resveratrol.

[0014] Preferably, the total mass ratio of the membrane material of the bicompartment liposome to the mass of the drug is (5-15):1 (e.g., it can be 5:1, 6:1, 7:1, 9:1, 10:1, 13:1, 15:1, etc.).

[0015] Preferably, the particle size of the drug-loaded bicompartment liposome is 100-200 nm (e.g., 100 nm, 120 nm, 140 nm, 160 nm, 180 nm, 200 nm, etc.).

[0016] In a second aspect, the present invention provides a method for preparing drug-loaded bicompartment liposomes as described in the first aspect, the method comprising: (1) Phospholipids, cholesterol, essential oil molecules, drugs and organic solvents are mixed, and the organic solvents are evaporated under reduced pressure to obtain a drug-containing lipid film; (2) The lipid film was hydrated by mixing with water and then extruded to obtain drug-loaded bicompartment liposomes.

[0017] This invention employs a vacuum evaporation and extrusion process, which can obtain liposome structures without the need for complex templates or special reaction conditions. The operation is simple and reproducible. By introducing essential oils to regulate the fluidity of the lipid membrane, the transformation of liposomes from monolayer vesicles to liposome structures can be achieved, and the structure formation process is controllable.

[0018] Preferably, the mixing temperature in step (1) is 20-30℃ (e.g., 20℃, 22℃, 24℃, 26℃, 28℃, 30℃, etc.), and the time is 3-20 min (e.g., 3 min, 5 min, 10 min, 15 min, 20 min, etc.).

[0019] Preferably, the temperature of the reduced pressure evaporation in step (1) is 30-40℃ (for example, it can be 30℃, 32℃, 34℃, 36℃, 38℃, 40℃, etc.).

[0020] Preferably, the organic solvent in step (1) includes any one or a combination of at least two of dichloromethane, chloroform, n-hexane, and cyclohexane.

[0021] Preferably, after obtaining the drug-containing lipid film in step (1), a drying step is further included, and the drying time is 10-24h (for example, it can be 10h, 12h, 14h, 16h, 18h, 20h, 24h, etc.).

[0022] Preferably, the hydration temperature in step (2) is 30-40℃ (e.g., 30℃, 32℃, 34℃, 36℃, 38℃, 40℃, etc.), and the time is 1-3 h (e.g., 1 h, 2 h, 3 h, etc.).

[0023] All other specific point values ​​not listed above within the numerical ranges mentioned above can be selected and are all within the protection scope of this invention. For the sake of brevity, they will not be described in detail here.

[0024] Thirdly, the present invention provides the use of drug-loaded bicompartment liposomes as described in the first aspect in the preparation of products for transdermal drug delivery.

[0025] Fourthly, the present invention provides the use of drug-loaded bicompartment liposomes as described in the first aspect in the preparation of products for anti-aging.

[0026] Compared with the prior art, the present invention has the following beneficial effects: This invention creatively designs a drug-loaded bicompartmental liposome. The liposome is prepared by introducing essential oil molecules into lecithin. These essential oil molecules can embed into the lipid bilayer, regulating the fluidity and microstructure of the phospholipid membrane. During lipid membrane extrusion, the membrane is induced to bend and indent, thereby stably forming a unique liposome structure with internally separated bicompartments. The prepared bicompartmental liposomes are characterized by uniform particle size, adjustable membrane fluidity, and good biocompatibility. Compared with traditional single-compartmental liposomes, the bicompartmental liposomes provided by this invention exhibit superior transdermal delivery performance as drug carriers, particularly excelling in promoting the skin penetration of hydrophobic drugs. This bicompartmental liposome can serve as a functional carrier for encapsulating different types of active substances, demonstrating excellent application potential. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the preparation process of the bicompartment liposomes of the present invention; Figure 2 The figures show the average particle size and polydispersity index (PDI) test results of the bicompartmental liposomes prepared in Example 1 of this invention and the single-compartmental liposomes obtained in Comparative Example 1; the left side of the figure shows the average particle size test results, and the right side shows the PDI test results. Figure 3 The images show the cryo-transmission electron microscopy observation results of the bicompartmental liposomes prepared in Example 1 of this invention and the single-compartmental liposomes obtained in the comparative preparation example 1. The left image is a cryo-transmission electron microscopy image of the bicompartmental liposomes, and the right image is a cryo-transmission electron microscopy image of the single-compartmental liposomes. Figure 4 The results of drug permeability tests for the drug-loaded bicompartment liposomes obtained in Example 1 and the drug-loaded monocompartment liposomes obtained in Comparative Example 1 are shown below. Figure 5 The results of β-galactosidase senescence staining evaluation of the drug-loaded bicompartment liposomes obtained in Example 1 and the drug-loaded monocompartment liposomes obtained in Comparative Example 1 are shown. Figure 6The contents of inflammatory factors IL-6 and IL-1β in the drug-loaded bicompartmental liposomes obtained in Example 1 and the drug-loaded monocompartmental liposomes obtained in Comparative Example 1 were measured to evaluate their anti-aging effects. Detailed Implementation

[0028] To further illustrate the technical means and effects of the present invention, the following describes the technical solution of the present invention in conjunction with preferred embodiments of the present invention. However, the present invention is not limited to the scope of the embodiments.

[0029] Preparation Example 1 This preparation provides a bicompartmental liposome, and the preparation method is as follows: (1) At 25°C, weigh 100 mg of soybean lecithin, 20 mg of cholesterol and 30 mg of linalool and dissolve them in 100 mL of chloroform. After sonication at 60 W for 5 minutes, a uniform pale yellow solution is formed. Evaporate the organic solvent at 37°C and under reduced pressure to form a lipid film on the inner wall of the container, and then dry for 12 hours for later use. (2) Add 100 mL of ultrapure water to the above lipid film and hydrate it at 37°C for 2 hours. Shake and vibrate every 5 minutes to obtain a liposome suspension. Extrude the liposome suspension through a 100 nm polycarbonate membrane to obtain a bicompartment liposome.

[0030] Comparative Preparation Example 1 This comparative preparation example provides a single-compartment liposome, prepared by the following method: (1) At 25°C, weigh 100 mg of soybean lecithin and 20 mg of cholesterol and dissolve them in 100 mL of chloroform. After sonication at 60 W for 5 minutes, a uniform pale yellow solution is formed. Evaporate the organic solvent at 37°C under reduced pressure to form a lipid film on the inner wall of the container, and then dry for 12 hours for later use. (2) Add 100 mL of ultrapure water to the above lipid film and hydrate it at 37°C for 2 hours. Shake and vibrate every 5 minutes to obtain a liposome suspension. Extrude the liposome suspension through a 100 nm polycarbonate membrane to obtain a single-chamber liposome.

[0031] Test Example 1 This test example characterizes the morphology of the bicompartmental liposomes prepared in Example 1 and the singlecompartmental liposomes prepared in Comparative Example 1.

[0032] Figure 2The graphs show the particle size distribution and polydispersity index (PDI) of the bicompartmental liposomes prepared in Example 1 and the monocompartmental liposomes prepared in Comparative Example 1. The results show that the prepared bicompartmental liposomes have a particle size distribution between 100 and 200 nm and a PDI less than 0.3, indicating that the bicompartmental liposomes have a uniform particle size distribution and good system homogeneity. The average particle size and PDI of the monocompartmental liposomes are slightly smaller than those of the bicompartmental liposomes.

[0033] Figure 3 The images show the results of cryo-transmission electron microscopy observation of the bicompartmental liposomes prepared in Example 1 of this invention and the single-compartmental liposomes prepared in Comparative Example 1. The images clearly show that the bicompartmental liposomes have a spherical or near-spherical structure, which is significantly different from the single-compartmental liposomes. The bicompartmental liposomes have obvious bicompartmental features inside, with the two compartments separated by a phospholipid bilayer, which confirms the structure of the bicompartmental liposomes.

[0034] Test Example 2 This test example measures the membrane fluidity of the bicompartmental liposomes prepared in Example 1 and the singlecompartmental liposomes prepared in Comparative Example 1.

[0035] Membrane fluidity was determined using a fluorescence anisotropy method. Using 1,6-diphenyl-1,3,5-hexadetriene (DPH) as a fluorescent probe, two-compartment liposomes from Preparation Example 1 and one-compartment liposomes from Comparative Preparation Example 1 were taken as samples and diluted with phosphate buffer (pH 7.4) to a phospholipid concentration of 1.0 mg / mL. 1.864 mL of each diluted liposome suspension was taken, and 2.5 mL of 2 μmol / L DPH aqueous solution was added. The volume was then adjusted to 5 mL with the above buffer and incubated at 25°C in the dark for 60 min.

[0036] After incubation, fluorescence spectrophotometers equipped with fluorescence polarization accessories were used for measurement. The excitation wavelength was set to 360 nm, the emission wavelength to 425 nm, and the slit width to 5 nm. The fluorescence intensity was measured under the following four polarization combinations: fluorescence intensity when both the excitation and emission polarizers were placed vertically (vertical / vertical polarization), fluorescence intensity when the excitation polarizer was vertical and the emission polarizer was horizontal (vertical / horizontal polarization), fluorescence intensity when the excitation polarizer was horizontal and the emission polarizer was vertical (horizontal / vertical polarization), and fluorescence intensity when both the excitation and emission polarizers were placed horizontally (horizontal / horizontal polarization).

[0037] Calculate the instrument correction factor G using the following formula: G = Horizontal / Vertical Polarization ÷ Horizontal / Horizontal Polarization.

[0038] Then calculate the fluorescence anisotropy value r using the following formula: r = (vertical / vertical polarization – G × vertical / horizontal polarization) ÷ (vertical / vertical polarization + 2 × G × vertical / horizontal polarization).

[0039] A higher anisotropy value r indicates lower membrane fluidity, while a lower r indicates higher membrane fluidity.

[0040] The test results are shown in Table 1: Table 1 The results showed that, compared with single-chambered liposomes, the addition of linalool to bichambered liposomes to form bichambered liposomes significantly improved the fluidity of the liposome membrane.

[0041] Example 1 This embodiment provides a drug-loaded N,N,N',N'-tetra(2-pyridylmethyl)ethylenediamine (chemical formula C... 26 H 28 The preparation method of N6,TPEN) bicompartmental liposomes is as follows: (1) At 25°C, weigh 100 mg of soybean lecithin, 20 mg of cholesterol, 20 mg of TPEN and 30 mg of linalool and dissolve them in 100 mL of chloroform. After sonication at 60 W for 5 minutes, a uniform pale yellow solution is formed. Evaporate the organic solvent at 37°C under reduced pressure to form a drug-containing lipid film on the inner wall of the container, and then dry for 12 hours for later use. 100 mL of ultrapure water was added to the drug-containing lipid film and hydrated at 37°C for 2 hours, with shaking every 5 minutes to obtain a liposome suspension. The liposome suspension was then extruded through a 100 nm polycarbonate membrane to obtain bicompartmental liposomes loaded with the drug TPEN.

[0042] Figure 1 This is a schematic diagram of the preparation process of the bicompartmental liposomes of the present invention.

[0043] Comparative Example 1 This comparative example provides a single-compartment liposome loaded with the drug TPEN, prepared by the following method: (1) At 25°C, weigh 100 mg of soybean lecithin, 20 mg of cholesterol, and 20 mg of TPEN and dissolve them in 100 mL of chloroform. After sonication at 60 W for 5 minutes, a uniform pale yellow solution is formed. Evaporate the organic solvent at 37°C under reduced pressure to form a drug-containing lipid film on the inner wall of the container. Then dry for 12 hours for later use. 100 mL of ultrapure water was added to the drug-containing lipid film and hydrated at 37°C for 2 hours, with shaking every 5 minutes to obtain a liposome suspension. The liposome suspension was then extruded through a 100 nm polycarbonate membrane to obtain single-chamber liposomes loaded with the drug TPEN.

[0044] Test Example 3 This test example measures the TPEN encapsulation efficiency of the two-compartment liposomes loaded with TPEN obtained in Example 1 and the one-compartment liposomes loaded with TPEN obtained in Comparative Example 1.

[0045] The TPEN loading and encapsulation efficiency (EE%) were verified using ultraviolet spectroscopy. The method was as follows: free TPEN in the two groups of samples was removed from the TPEN-encapsulated liposome suspension by centrifugation (centrifugal force 4000g). Subsequently, the liposome suspensions of each group were lysed with ethanol, and the absorption peak intensity at 262 nm of the lysate was measured by ultraviolet spectroscopy.

[0046] The formula for calculating EE% is: Where Wt is the mass of TPEN encapsulated in the liposomes, and W is the total mass of TPEN added to prepare the composite material.

[0047] Experimental results showed that the encapsulation efficiencies of bicompartmental and monocompartmental liposomes encapsulated with TPEN were 78.89 ± 0.55% and 69.48 ± 0.91%, respectively, indicating that bicompartmental vesicles had significantly higher encapsulation efficiencies.

[0048] Test Example 4 This test example demonstrates the transdermal performance of the two-compartment liposomes loaded with TPEN obtained in Example 1 and the single-compartment liposomes loaded with TPEN obtained in Comparative Example 1.

[0049] The TPEN-loaded bicompartmental liposomes obtained in Example 1 and the TPEN-loaded monocompartmental liposomes obtained in Comparative Example 1 were used as test samples. Using a Franz diffusion cell apparatus, mouse skin was fixed between the donor and recipient compartments. 1 mL of the test sample was added to the donor compartment, and 6.5 mL of PBS solution containing 30% ethanol was added to the recipient compartment. Transdermal experiments were conducted at 32°C over 48 hours. Samples were taken from the recipient compartment at 2, 4, 6, 8, 12, 18, 24, 36, and 48 hours, and the TPEN permeation was determined by ultraviolet spectrophotometry.

[0050] The results are as follows Figure 4 As shown. The results indicate that the drug permeability of the TPEN-loaded bicompartmental liposomes obtained in Example 1 of the present invention is good, and significantly higher than that of the TPEN-loaded monocompartmental liposomes in Comparative Example 1.

[0051] Test Example 5 This test case evaluates the anti-cellular aging effects of the two-compartment liposomes loaded with TPEN obtained in Example 1 and the one-compartment liposomes loaded with TPEN obtained in Comparative Example 1.

[0052] Establishment of a cell senescence model: Human dermal fibroblasts (HDF) were cultured in 96-well plates, with approximately 1 × 10⁶ cells seeded per well. 4 6 × 10⁶ cells have reached the logarithmic growth phase (approximately 6 × 10⁶ cells). 4 At a cell / well ratio of 1,000 cells, cells were divided into five groups: a control group, a bleomycin group, and two treatment groups: a TPEN-loaded single-compartment liposome group (Comparative Example 1) and a TPEN-loaded double-compartment liposome group (Example 1). Except for the control group, all other groups were treated with bleomycin (50 μg / mL) for 24 hours to induce cell senescence. After treatment, the drug-containing medium was discarded, and fresh DMEM complete medium was added for further culture for 6 days to establish a stable senescent phenotype.

[0053] During model establishment, cells in the treatment groups were treated with either TPEN-loaded single-compartment liposomes (Comparative Example 1) or TPEN-loaded double-compartment liposomes (Example 1), and the culture medium was changed every two days. Cells in the control group were treated with only an equal volume of drug-free complete culture medium, while the bleomycin group was treated with only bleomycin. After model establishment, subsequent detection of cell anti-aging related indicators was performed.

[0054] The senescence level of HDF cells was detected using β-galactosidase (SA-β-gal) staining. After treatment, the culture medium was discarded from each group of HDF cells, and the cells were gently washed twice with PBS buffer. 1 mL of fixative was added to each well, and the cells were fixed at room temperature for 15 minutes. The fixative was then discarded, and the cells were washed three times with PBS. Using the SA-β-gal staining kit (purchased from Beyotime), the staining working solution was prepared according to the manufacturer's instructions. 1 mL of the staining working solution was added to each well, and the edges of the 6-well plate were sealed with sealing film to prevent evaporation. The cells were incubated at 37°C in the dark and without CO2 for 12 hours. After staining, the staining solution was discarded, and the cells were washed with PBS. The staining was observed and photographed under an inverted optical microscope. Senescent cells showed a blue positive stain. Three fields of view were randomly selected from each group to calculate the positive cell rate.

[0055] Figure 5 The β-galactosidase aging staining evaluation was performed. The results showed that the TPEN-loaded bicompartmental liposomes of Example 1 of this invention could significantly reduce the β-galactosidase positivity rate of HDF cells, and its anti-aging effect was significantly better than that of TPEN-loaded monocompartmental liposomes.

[0056] The levels of inflammatory cytokines IL-6 and IL-1β in HDF cell culture supernatant were determined using enzyme-linked immunosorbent assay (ELISA). Cell culture supernatants from each group were collected, and human IL-6 and IL-1β ELISA kits (purchased from ELISA kit manufacturers) were used according to the manufacturer's instructions. Standards were serially diluted to plot a standard curve. 100 μL of standards and diluted samples were added to pre-coated antibody-impregnated ELISA plates, and incubated at 37°C for 2 hours. After washing, biotinylated detection antibody was added, and the plates were incubated at 37°C for 1 hour. After washing again, horseradish peroxidase-labeled streptavidin was added, and the plates were incubated at 37°C in the dark for 20 minutes. TMB chromogenic substrate was added, and the plates were incubated at 37°C in the dark for 15 minutes. Stop solution was added, and the absorbance (OD) of each well was measured at 450 nm. The concentrations of IL-1β and IL-6 in the samples were calculated based on the standard curve.

[0057] Figure 6 The levels of inflammatory factors IL-6 and IL-1β were measured to evaluate the anti-aging effect. The results showed that the TPEN-loaded bicompartmental liposomes of Example 1 of the present invention could significantly reduce the levels of inflammatory factors IL-1β and IL-6 in HDF cells, and its anti-aging effect was superior to that of TPEN-loaded monocompartmental liposomes.

[0058] The applicant declares that the technical solution of this invention is illustrated by the above embodiments, but this invention is not limited to the above embodiments, that is, it does not mean that this invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials for the products of this invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of this invention.

[0059] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0060] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. A drug-loaded bicompartment liposome, characterized in that, The drug-loaded bicompartmental liposome includes a bicompartmental liposome and a drug encapsulated within the bicompartmental liposome; The bicompartmental liposome includes a first liposome and a second liposome encapsulated within the first liposome. The first liposome and the second liposome have their own independent lipid bilayers, and the drug is encapsulated within the lipid bilayers of the respective first liposome and the second liposome. The membrane material of the bicompartmental liposome includes phospholipids, cholesterol, and essential oil molecules.

2. The drug-loaded bicompartment liposome according to claim 1, characterized in that, The drug is embedded in the hydrophobic region of the lipid bilayer of each of the independent first and second liposomes.

3. The drug-loaded bicompartment liposome according to claim 1 or 2, characterized in that, The mass ratio of the phospholipids, cholesterol, and essential oil molecules is (5-15):(1-3):(1-5).

4. The drug-loaded bicompartment liposome according to claim 3, characterized in that, The phospholipids include any one or a combination of at least two of soybean lecithin, hydrogenated lecithin, and egg yolk lecithin. Preferably, the essential oil molecule is a monoterpenoid compound; Preferably, the essential oil molecules include any one or a combination of at least two of linalool, geraniol, tetrahydrogeraniol, citronellol, citral, α-terpineol, 4-terpineol, menthol, camphor, and carvone.

5. The drug-loaded bicompartment liposome according to any one of claims 1-4, characterized in that, The drug is a lipid-soluble small molecule drug; Preferably, the drug comprises any one or a combination of at least two of N,N,N',N'-tetra(2-pyridylmethyl)ethylenediamine, ruxotinib, quercetin, and resveratrol; Preferably, the total mass ratio of the membrane material of the bicompartment liposome to the mass ratio of the drug is (5-15):

1.

6. The drug-loaded bicompartment liposome according to any one of claims 1-5, characterized in that, The particle size of the drug-loaded bicompartment liposomes is 100-200 nm.

7. The method for preparing drug-loaded bicompartment liposomes according to any one of claims 1-6, characterized in that, The preparation method includes: (1) Phospholipids, cholesterol, essential oil molecules, drugs and organic solvents are mixed, and the organic solvents are evaporated under reduced pressure to obtain a drug-containing lipid film; (2) The lipid membrane was hydrated by mixing with water and then extruded to obtain drug-loaded bicompartment liposomes.

8. The preparation method according to claim 7, characterized in that, The mixing temperature in step (1) is 20-30℃, and the time is 3-20 min; Preferably, the temperature of the reduced pressure evaporation in step (1) is 30-40°C; Preferably, the organic solvent in step (1) includes any one or a combination of at least two of dichloromethane, trichloromethane, n-hexane, and cyclohexane; Preferably, after obtaining the drug-containing lipid film in step (1), a drying step is further included, and the drying time is 10-24 h; Preferably, the hydration temperature in step (2) is 30-40℃ and the time is 1-3 h.

9. Use of the drug-loaded bicompartment liposome according to any one of claims 1-6 in the preparation of products for transdermal drug delivery.

10. The use of the drug-loaded bicompartment liposomes according to any one of claims 1-6 in the preparation of products for anti-aging.

Images