Liposome compositions and methods for their preparation

Abstract

The present application provides a method for preparing a liposome composition. In the method, a containing step is provided, including: providing precursor liposomes wrapping a platinum drug precursor; and culturing the precursor liposomes in a salt solution to convert the platinum drug precursor into a platinum drug to obtain the liposome composition. The precursor liposomes are obtained by the following steps: hydrating the platinum drug to obtain the platinum drug precursor; and adding the platinum drug precursor to a lipid bilayer carrier to obtain the precursor liposomes. The liposome composition prepared by the method has better coating rate and stronger drug loading capacity.

Description

Technical Field

[0001] This patent application claims the entire contents of U.S. Provisional Application No. 62 / 987366, filed March 10, 2020, which are incorporated herein by reference.

[0002] This invention relates to a liposome composition, and more particularly to a liposome composition encapsulating a platinum-based drug precursor and its preparation method. Background Technology

[0003] Cis-diaminedichloroplatinum (II), CDDP, also known as cisplatin, is a well-known and commonly used chemotherapy drug. However, this drug has drawbacks such as poor water solubility and high toxicity, which can lead to a variety of adverse side effects. Summary of the Invention

[0004] To improve the solubility of cis-diamine dichloroplatinum and reduce its toxicity, some embodiments of the present invention provide a method for preparing a liposome composition. This method includes the steps of: providing precursor liposomes encapsulating a platinum-based drug precursor; and culturing the precursor liposomes in a salt solution to convert the platinum-based drug precursor into a platinum-based drug, thereby forming the liposome composition.

[0005] Another embodiment of the present invention provides a method for preparing a liposome composition. This method includes the steps of: providing salt-encapsulated liposomes; and mixing the salt liposomes with a platinum-based drug precursor to allow the platinum-based drug precursor to enter the salt liposomes and react with the salt, thereby converting the platinum-based drug precursor into a platinum-based drug to form the liposome composition.

[0006] Another embodiment of the present invention provides a method for preparing a liposome composition. This method includes the steps of: providing precursor liposomes encapsulating a platinum-based drug precursor, and providing salt liposomes encapsulating a salt; and mixing the precursor liposomes and the salt liposomes to convert the platinum-based drug precursor into a platinum-based drug to form a liposome composition.

[0007] Another embodiment of the present invention provides a method for preparing a liposome composition. This method includes the steps of: providing a precursor core encapsulating a platinum-based drug precursor and providing a salt core encapsulating a salt; mixing the precursor core and the salt core to convert the platinum-based drug precursor into a platinum-based drug to form a liposome core; and mixing the liposome core with a first lipid formulation to form a liposome composition.

[0008] Another embodiment of the present invention provides a liposome composition. This liposome composition is prepared by any of the aforementioned preparation methods. The drug loading rate (%) of this liposome composition is at least 10%.

[0009] The liposome compositions according to any embodiment of the present invention provide an effective solution for improving the solubility of platinum-based drugs and the encapsulation rate of liposome particles. Through the preparation methods of the embodiments of the present invention, precursor liposomes can be conveniently and cost-effectively converted into platinum-based drugs encapsulated in liposomes. These preparation methods also provide an effective tool for improving the drug loading rate (%) of liposome compositions. Attached Figure Description

[0010] Figure 1 This is a schematic diagram of the chemical reaction for preparing a liposome composition according to an exemplary embodiment of the present invention.

[0011] Figure 2 This is a schematic diagram of the chemical reaction for the preparation of a cis-diamine dichloroplatinum precursor (CDDP precursor) of a liposome composition according to an exemplary embodiment of the present invention.

[0012] Figure 3 This is a schematic diagram of the chemical reaction for preparing a liposome composition according to another exemplary embodiment of the present invention.

[0013] Figure 4 This is a schematic diagram of the chemical reaction for preparing a liposome composition according to another exemplary embodiment of the present invention.

[0014] Figure 5 This is a schematic diagram of the chemical reaction for preparing a liposome composition according to another exemplary embodiment of the present invention.

[0015] Figure 6 This is a cryogenic electron microscopy (Cryo-EM) image of a liposome composition according to an exemplary embodiment of the present invention.

[0016] Figure 7 This is a diagram showing the size distribution of a liposome composition according to an exemplary embodiment of the present invention.

[0017] Figure 8 The figure shows the pharmacokinetic analysis results of the liposome composition in an animal model according to an exemplary embodiment of the present invention.

[0018] Figure 9 The figures show the tumor growth rate and tumor volume changes in a mouse model of xenografting H1975 adenocarcinoma cells of human non-small-cell lung cancer (NSCLC) after treatment with phosphate-buffered saline (PBS), cis-diamine dichloroplatin, and a liposome composition (hereinafter referred to as LipoCis) encapsulated in a lipid bilayer carrier.

[0019] Figure 10 Figures showing the tumor growth rate, tumor volume, and weight changes in a mouse model of A549 cell xenograft after treatment with phosphate-buffered saline and LipoCis, respectively.

[0020] Figure 11 The graph shows the tumor volume, body weight, tumor growth rate, and body weight changes in H460 cell xenograft mouse model after treatment with phosphate-buffered saline and LipoCis, respectively, in response to dosage changes.

[0021] Figure 12 The image shows the tumor volume changes in a mouse model of human oral squamous cell carcinoma (HOSCC) SAS cell xenograft after treatment with phosphate-buffered saline, cis-diamine dichloroplatin, and LipoCis, respectively.

[0022] Figure 13 This image shows the tumor shrinkage effect of metastatic SAS cells in a mouse model of human oral squamous cell carcinoma according to an exemplary embodiment of the present invention.

[0023] None of the attached figures are labeled. Detailed Implementation

[0024] The invention will be more fully understood through the following detailed description, which is for illustrative purposes only and not for limiting the invention.

[0025] Please see Figure 1 In a first embodiment of the present invention, a method for preparing a liposome composition is provided. This method may include the steps of: providing precursor liposomes encapsulating a platinum-based drug precursor; and culturing the precursor liposomes in a salt solution to convert the platinum-based drug precursor into a platinum-based drug to form a liposome composition. Specifically, the precursor liposomes may be prepared by the following steps: hydrating a platinum-based drug to form a platinum-based drug precursor; and adding the platinum-based drug precursor to a lipid bilayer carrier to form precursor liposomes.

[0026] Hydration of platinum-based drugs can be achieved by culturing them with silver nitrate (AgNO3), silver sulfate (Ag2SO4), silver phosphate (Ag3PO4), calcium nitrate (Ca(NO3)2), calcium sulfate (CaSO4), calcium phosphate (Ca3(PO4)2), magnesium nitrate (Mg(NO3)2), magnesium sulfate (MgSO4), and / or magnesium phosphate (Mg(H2PO4)2).

[0027] In some embodiments, platinum-based drugs may contain at least one platinum-halides bond (e.g., a platinum-fluorine bond, a platinum-chloride bond, a platinum-bromine bond, or a platinum-iodine bond). In some examples, platinum-based drugs may contain cisplatin, triplatin, phenanthriplatin, picoplatin, satraplatin, cis-diaminediiodoplatin(II), cis-diaminedifluoroplatin(II), and cis-diaminedibromoplatin(II).

[0028] Please see Figure 2 Platinum-based drug precursors can be monoaqua and / or diaqua platinum-based drugs; for example, cis -[Pt(NH3)2(H2O)2](NO3)2 or cis -[Pt(NH3)2(H2O)2] 2+ Due to their water-soluble properties, platinum-based drug precursors can be encapsulated by lipid bilayer carriers (such as liposome nanoparticles).

[0029] The lipid bilayer carrier can be prepared by mixing a lipid formulation with an organic solution, such as chloroform, cyclohexane, methanol, ethanol, or any combination thereof. The lipid formulation may comprise a composition consisting of choline phospholipids, cholesterol, and a PEG-based compound. Preferably, choline phospholipids may comprise neutral lipids, such as: 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and hexadecyl phosphocholine (hexadecyl phosphocholine). Phosphorylcholine (HePC), 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), 1,2-diphytanoyl-sn-glycero-3-phosphocholine (diPhyPC), or any combination thereof.Compounds containing polyethylene glycol can be distearoylphosphatidyl ethanolamine (DSPE)-PEG compounds, such as: N-(carbonyl-methoxypolyethylene glycol-200)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, polyethylene glycol 200-distearoylphosphatidyl ethanolamine (DSPE-PEG-200). Or DSPE-mPEG-200), polyethylene glycol 400-distearylphosphatidylethanolamine (DSPE-PEG-400 or DSPE-mPEG-400), polyethylene glycol 800-distearylphosphatidylethanolamine (DSPE-PEG-800 or DSPE-mPEG-800), polyethylene glycol 1000-distearylphosphatidylethanolamine (DSPE-PEG-1000 or DSPE-mPEG-1000), polyethylene glycol 2000-distearylphosphatidylethanolamine (DSPE-PEG-2000 or DSPE-mPEG-2000), polyethylene glycol 2500-distearylphosphatidylethanolamine (DSPE-PEG-2500 or DSPE-mPEG-2500), polyethylene glycol 3000-distearylphosphatidylethanolamine (DSPE-PEG-3000), Alternatively, the polyethylene glycol (PEG) compound may be selected from DSPE-mPEG-3000, polyethylene glycol 4000-distearylphosphatidylethanolamine (DSPE-PEG-4000, or DSPE-mPEG-4000), polyethylene glycol 5000-distearylphosphatidylethanolamine (DSPE-PEG-5000, or DSPE-mPEG-5000), polyethylene glycol 6000-distearylphosphatidylethanolamine (DSPE-PEG-6000, or DSPE-mPEG-6000), polyethylene glycol 10000-distearylphosphatidylethanolamine (DSPE-PEG-10000, or DSPE-mPEG-10000), or any combination thereof. In some embodiments, the polyethylene glycol (PEG)-containing compound may be selected from DSPE-PEG-aminoethyl-p-methoxybenzamide (DSPE-PEG-aminoethyl-p-methoxybenzamide). anisamide, DSPE-PEG-AEAA, DSPE-PEG-monoclonal antibody (DSPE-PEG-mAb), and DSPE-PEG with other ligand moieties.

[0030] The lipid formulation can be a self-assembling lipid bilayer carrier in an aqueous environment via hydrophobic interactions and / or van der Waals interactions. In one or more preferred embodiments, the neutral nature of the lipid formulation provides the minimum energy required to bond with the encapsulated active pharmaceutical ingredient (API) or its precursor, thereby promoting drug release in vivo. Furthermore, because the neutral lipid bilayer carrier does not interact with charged precursors, the drug conversion process occurring therein is not affected or hindered.

[0031] In some embodiments, the volume ratio of the lipid bilayer carrier to the cis-diamine dichloroplatinum precursor in the liposome composition is in the range of 1:1 to 20:1. The molar ratio of the cis-diamine dichloroplatinum precursor to the lipid bilayer carrier is in the range of 0.1:1 to 1:1. The cis-diamine dichloroplatinum precursor is added to the lipid bilayer carrier, and its volume ratio (i.e., the oil to water ratio) is in the range of 1:0.01 to 1:0.8. The molar concentration of the platinum drug precursor in the lipid bilayer carrier or in the precursor liposomes is in the range of 25 mM to 600 mM, preferably in the range of 1.5 mM to 5 mM.

[0032] To convert a platinum-based drug precursor into a platinum-based drug, precursor liposomes can be cultured in a salt solution to allow salt to enter the precursor liposomes. In this embodiment, the salt solution may contain other salts of fluoride, chloride, bromide, iodide, or halogen groups. The volumetric molar concentration of the salt solution is in the range of 0.2 M to 4 M; specifically, when sodium chloride is used as the salt in the aforementioned conversion, the volumetric molar concentration of sodium chloride can be in the range of 0.4 M to 3.9 M; when potassium chloride is used as the salt in the aforementioned conversion, the volumetric molar concentration of potassium chloride can be in the range of 0.4 M to 3.0 M. In some embodiments, the precursor liposomes may be cultured in a salt solution at 4-65°C for 1-24 hours to allow salt to enter the precursor liposomes and to convert the dihydrate cis-diaminedichloroplatinum precursor into cis-diaminedichloroplatinum. For example, precursor liposomes can be cultured overnight in a salt solution at 4-7°C, or cultured in a salt solution at 10-50°C for 2-15 hours and then cooled to stabilize the structure of the liposome composition.

[0033] In one or more embodiments, the high concentration of salt solution generates osmotic pressure that irreversibly pushes halide ions through the lipid bilayer carrier, while retaining them within the precursor liposomes without affecting the stability of the liposome structure. Because the halide ions within the precursor liposomes are consumed for the conversion of the active ingredient into the drug, more halide ions continuously diffuse into the precursor liposomes. This osmotic-based method provides a cost-effective and time-efficient pathway for driving drug conversion within precursor liposomes.

[0034] In the first embodiment, to prepare a liposome composition (hereinafter referred to as LipoCis) consisting of a lipid bilayer carrier composed of distearylphosphatidylcholine, cholesterol, and polyethylene glycol 2000-distearylphosphatidylethanolamine and encapsulating cis-diamine dichloroplatin as a platinum-based drug, the cis-diamine dichloroplatin precursor can be prepared by dissolving 0.2-0.4 mmol of cis-diamine dichloroplatin in 0.3-0.4 mmol of an aqueous solution of silver nitrate (AgNO3). 3(aq) The mixture is prepared by incubating at 25°C for 16-18 hours or at 60°C for 3-4 hours. Next, at 30-60°C and 100-400 rpm, distearylphosphatidylcholine, cholesterol, and polyethylene glycol 2000-distearylphosphatidylethanolamine are mixed at a weight ratio of 40-50:25-50:10-30 w / w% for 10-60 minutes to form a lipid bilayer carrier. Then, the cis-diamine dichloroplatinum precursor is added to the lipid bilayer carrier at a volume ratio of oil to water of 1:0.01 to 1:0.8. This addition can be done using a microdropper at a rate of 1 mL / min, or by hand shaking or mixing with a stir bar for 15-30 minutes to form precursor liposomes. Then, the aforementioned liposomes encapsulating the cis-diamine dichloroplatinum precursor were homogenized by 1-10 cycles to obtain liposomes with a size of 60-250 nm. Finally, the homogenized precursor liposomes were cultured in 0.2-3.9 M potassium chloride or sodium chloride solution at 25-50 °C with uniform stirring for 2-24 hours to convert the cis-diamine dichloroplatinum precursor in the liposomes into cis-diamine dichloroplatinum. Then, excess salt was removed using a tangential flow filtration (TFF) system to purify the product LipoCis. This product was then stored in a buffer solution containing 10 mM HEPE and 5% glucose (pH 6.5-7.6), a buffer solution containing 10 mM HEPE and 0.9% saline (pH 6.5-7.6), a solution containing 0.9% saline and 5% glucose, or deionized water. The resulting product, LipoCis, has a drug-to-lipid (D / L) ratio that can reach 0.05-0.8 per mole.

[0035] Please see Figure 3In a second embodiment, another method for preparing a liposome composition is provided. This method includes the steps of: providing salt-encapsulated liposomes; and culturing the salt liposomes and a platinum-based drug precursor to allow the platinum-based drug precursor to enter the salt liposomes and react with the salt, thereby converting the platinum-based drug precursor into a platinum-based drug to form a liposome composition. Specifically, the salt liposomes can be prepared by adding salt to a lipid bilayer carrier. The details of the components and steps used in the preparation method of the second embodiment are similar to those described in the first embodiment; please refer to the related description above.

[0036] Please see Figure 4 In a third embodiment, another method for preparing a liposome composition is provided. This method includes the steps of: providing precursor liposomes encapsulating a platinum-based drug precursor, and providing salt liposomes encapsulating a salt; and mixing the precursor liposomes and salt liposomes to convert the platinum-based drug precursor into a platinum-based drug to form a liposome composition. Specifically, the precursor liposomes can be prepared by the following steps: hydrating the platinum-based drug to form a platinum-based drug precursor; and adding the platinum-based drug precursor to a lipid bilayer carrier to form the precursor liposomes. Similarly, the salt liposomes can be prepared by adding a salt to a lipid bilayer carrier to form salt liposomes. The details of the components and steps used in the preparation method of the third embodiment are similar to those described in the first embodiment; please refer to the relevant description above.

[0037] Please see Figure 5 In the fourth embodiment, another method for preparing a liposome composition is also provided. This method includes the steps of: providing a precursor core encapsulating a platinum-based drug precursor and providing a salt core encapsulating a salt; mixing the precursor core and the salt core to convert the platinum-based drug precursor into a platinum-based drug to form a liposome core; and mixing the liposome core with a first lipid formulation to form a liposome composition. Specifically, the precursor core can be obtained by the following steps: hydrating the platinum-based drug to form a platinum-based drug precursor; and adding the platinum-based drug precursor to a lipid bilayer carrier to form the precursor core. Similarly, the salt core can be obtained by the step of adding salt to a lipid monolayer carrier to form a salt core. The details of the components and steps used in the preparation method of the fourth embodiment are similar to those described in the first embodiment; please refer to the relevant description above.

[0038] In some embodiments, the first lipid formulation may comprise cholesterol and a polyethylene glycol-containing compound. The first lipid formulation may be dissolved in an organic solution (e.g., chloroform, ethanol) and then mixed with the liposome core at 25-45°C for 25-60 minutes. For example, such as... Figure 5 As shown, after the addition of the lipid formulation, cholesterol stabilizes the monolayer liposome core, and polyethylene glycol 2000-distearatephosphatidylethanolamine coats the outside of this liposome core, creating a bilayer liposome composition.

[0039] Lipid monolayer carriers can be prepared by mixing a second lipid formulation dissolved in an organic solution (e.g., chloroform, ethanol). This second lipid formulation may contain distearate phosphatidylcholine and / or other choline phospholipids. When using chloroform or other oil solutions, the lipid monolayer carrier can form immediately in these solutions. In water-miscible systems (e.g., ethanol), heating to 45-60°C for 15-30 minutes may be required to form the lipid monolayer carrier.

[0040] As demonstrated in Table 1, the high conversion rate and drug loading (%) of the aforementioned preparation method of the present invention can effectively encapsulate and convert platinum-based drug precursors into platinum-based drugs. Accordingly, the liposome composition prepared by the preparation method of the present invention can achieve a calculated drug loading (%) as high as 62%.

[0041] Table 1. Drug loading (DL) of LipoCis in the examples (%)

[0042]

[0043] Please see Figure 6 and Figure 7 In one example, cis-diamine dichloroplatinum is encapsulated and precipitated within a lipid bilayer composed of distearylphosphatidylcholine, cholesterol, and polyethylene glycol 2000-distearylphosphatidylethanolamine, forming LipoCis nanoparticles (NPs). These LipoCis nanoparticles can be identified using various methods. Figure 6 and Figure 7In the example shown, the particle size and zeta potential of LipoCis nanoparticles were measured using a nanoparticle size and potential analyzer (a Zetasizer Nano series instrument manufactured by Malvern, Inc.). The morphology of the LipoCis nanoparticles was observed using cryo-electron microscopy. The amount of cis-diamine dichloroplatinum was measured using high-performance liquid chromatography (HPLC). The platinum content in the LipoCis nanoparticles was measured using inductively coupled plasma-atomic emission spectroscopy (ICP-AES) or inductively coupled plasma-optical emission spectroscopy (ICP-OES). The excipient concentration was measured using HPLC volatile light scattering detectors (ELSD). Figure 6 As shown, the LipoCis nanoparticles captured by cryo-electron microscopy exhibit complete and uniform monodispersity, with an estimated particle size in the range of 80-150 nm. This result is consistent with the measurement results obtained by dynamic light scattering (DLS). Figure 7 As shown, all interaction polymer chromatography (IPC) values ​​of LipoCis nanoparticles were measured.

[0044] Please see Figure 8The pharmacokinetics of LipoCis prepared according to the first embodiment of the present invention were analyzed in a rat animal model. As shown in Table 2, LipoCis exhibits low clearance (CL), high area under curve (AUC), and long circulation time in vivo (i.e., the volume of distribution (Vz) and steady-state volume of distribution (Vss) of LipoCis are lower than those of the active ingredient). Based on the measurements of drug half-life and mean residence time (MRT), there was no statistically significant difference between LipoCis and the active ingredient. These pharmacokinetic results indicate that LipoCis possesses sustained-release properties in vivo.

[0045] Table 2

[0046]

[0047] To evaluate the inhibitory potential of LipoCis on tumor growth, a 21-day xenograft experiment will be conducted, with daily observation of the xenograft animals. In the experiment, human cancer cell lines (1x10⁻¹²) will be used. 6 1 cell / 200 μL of phosphate-buffered saline-Martigel 1:1 solution was subcutaneously injected into the right hind leg of Balb / c nude mice. After a clearly sized tumor appeared, the tumor size was measured daily or every other day and calculated using the formula (length x width x height) / 2. When the tumor size reached a predetermined size (e.g., 100-210 mm), the tumor was considered complete. 3 The mice in the LipoCis group were given intravenous injections of the drug once a week for 3 weeks.

[0048] Please see Figures 9 to 11 Three lung cancer cell lines (human non-small cell lung cancer H1975 and A549 cells, and human large cell carcinoma H460 cells) were used in experiments to detect the in vivo efficiency of LipoCis nanoparticles. Figure 9 As shown, in a mouse model of xenografting lung adenocarcinoma H1975 cells, the LipoCis treatment prepared according to the embodiments of the present invention exhibited a significant apoptosis response (based on immunostaining results), and compared with the results of cis-dichloroplatin treatment, the LipoCis treatment showed a stronger tumor-suppressive effect. Figures 10 to 11As shown, similar experimental results can be observed in both xenograft mouse models of lung adenocarcinoma A549 cells and xenograft mouse models of lung large cell carcinoma H460 cells.

[0049] Please refer to Figure 12 and Figure 13 To establish a human oral squamous cell carcinoma (HOSCC) xenograft animal model. Each 200 μL of Martigel (Martigel cell culture medium manufactured by Corning Life Sciences, Inc.) contained 5 x 10⁸ cells. 6 One hundred and sixty-six human oral cancer SAS cells were extracted and subcutaneously injected into 7- to 9-week-old male nude mice (strain name BALB / cAnN.Cg-) using a 28-gauge needle. Foxn1 nu The tumor was purchased from the Taipei Laboratory Animal Center in Taiwan, China. Mice with SAS cell xenografts were randomly divided into three groups and treated with the following drugs: (i) phosphate-buffered saline solution; (ii) cis-diamine dichloroplatin; and (iii) LipoCis nanoparticles. All drug treatments were administered intravenously. Cis-diamine dichloroplatin and LipoCis nanoparticles were both administered at a dose of 3.0 mg / kg. When the tumor size reached 200.1 mm... 3 ±3.5 (or 195-210mm) 3 Drug administration was only performed when the tumor was within a certain range. Tumor size was calculated using the formula: length x width x height x 0.5. Mice in each group were sacrificed on day 12 for data collection. The excised tumors and organs were sectioned and fixed in 10% formalin for subsequent experiments.

[0050] To verify the efficiency of LipoCis nanoparticles in vivo, tumors with a volume of 200.1 ± 3.5 mm were used. 3 Mice undergoing xenografting of SAS cells were randomly divided into three groups: (i) a group treated with phosphate buffered saline solution; (ii) a group treated with cis-diamine dichloroplatin; and (iii) a group treated with LipoCis nanoparticles. Each group received two drug treatments, with an interval of 6 days between each treatment. (Similar to...) Figure 9 and Figure 10 The experimental results shown indicate that LipoCis also has the potential to inhibit tumor growth in SAS cells.

[0051] According to the embodiments of the present invention described above, LipoCis provides an effective solution that can improve the solubility of platinum-based drugs and the encapsulation rate of liposome particles. Through the preparation methods of the embodiments of the present invention, precursor liposomes can be conveniently and cost-effectively converted into platinum-based drugs encapsulated in liposomes. These preparation methods also provide an effective tool for improving the drug loading (%) of liposome compositions.

[0052] While the technical content of the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the invention. Conversely, any modifications and similar refinements made without departing from the scope and spirit defined in the appended claims should be covered within the scope of the present invention. The scope defined herein should be interpreted in the broadest possible sense to encompass such modifications and similar refinements.

Claims

1. A method for preparing a liposome composition, characterized in that, Include: Provides a precursor liposome encapsulating a platinum-based drug precursor; and The precursor liposomes are cultured in a salt solution to convert the platinum-based drug precursor into a platinum-based drug, thereby forming the liposome composition; the salt solution contains fluoride, chloride, bromide, or iodide; the platinum-based drug contains at least one platinum halide bond. The precursor liposomes are prepared through the following steps: The platinum-based drug is hydrated to form the platinum-based drug precursor; The lipid formulation is mixed to form a lipid bilayer carrier; and The platinum-based drug precursor is added to the lipid bilayer carrier to form the precursor liposomes. The step of hydrating the platinum drug involves culturing the platinum drug with at least one compound, wherein the at least one compound is selected from the group consisting of silver nitrate, silver sulfate, silver phosphate, calcium nitrate, calcium sulfate, calcium phosphate, magnesium nitrate, magnesium sulfate, and magnesium phosphate. The lipid formulation comprises distearylphosphatidylcholine, cholesterol, and one selected from the group consisting of polyethylene glycol 2000-distearylphosphatidylethanolamine, polyethylene glycol 3000-distearylphosphatidylethanolamine, polyethylene glycol 4000-distearylphosphatidylethanolamine, polyethylene glycol 5000-distearylphosphatidylethanolamine, and polyethylene glycol 10000-distearylphosphatidylethanolamine.

2. The method as described in claim 1, characterized in that, The lipid formulation is mixed in an organic solution containing chloroform or ethanol.

3. The method as described in claim 1, characterized in that, In the step of adding the platinum-based drug precursor to the lipid bilayer carrier, the volume ratio of the lipid bilayer carrier to the platinum-based drug precursor is in the range of 1:0.01 to 1:0.

8.

4. The method as described in claim 1, characterized in that, The platinum-based drugs are selected from the group consisting of cisplatin, triplatin, phenanthreneplatin, pyrplatin, and ceterplatin.

5. The method as described in claim 1, characterized in that, The platinum drug precursor is at least one of the monohydrate form of the platinum drug and the dihydrate form of the platinum drug.

6. The method as described in claim 1, characterized in that, The volumetric molar concentration of the salt solution used to culture the precursor liposomes is in the range of 0.2 M to 4 M.

7. The method as described in claim 1, characterized in that, The precursor liposomes were cultured in the salt solution at 4-65°C for 1-24 hours.

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