A kind of garcinia acid freeze-dried emulsion and its preparation method and application

Abstract

The invention discloses a lyophilized emulsion of garcinia acid and a preparation method and application thereof. The lyophilized emulsion of garcinia acid is prepared from garcinia acid, an oil phase, chitosan, water, glacial acetic acid, sodium hydroxide and a lyophilization protective agent. The lyophilized emulsion of garcinia acid prepared by the invention solves the problem of poor water solubility of garcinia acid, improves drug solubility, and can reduce toxic and side effects on normal tissues, improve oral bioavailability, and improve drug efficacy through the drug release characteristics of Pickering emulsion.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to a lyophilized emulsion of garcinia acid and a preparation method and application thereof. Background Art

[0002] Garcinia acid is a caged xanthone compound extracted from the dry resin of the natural plant Garcinia cambogia, and is one of the main active ingredients of Garcinia. Garcinia acid has strong anti-cancer activity and has certain therapeutic effects on cancers such as gastric cancer, lung cancer, breast cancer, lymphoma, and skin cancer, while having no effect on the normal hematopoietic system and leukocytes. However, the water solubility of garcinia acid is extremely poor. Although the water solubility is enhanced under alkaline conditions, excessive pH values ​​will lead to the hydrolysis of garcinia acid. At the same time, garcinia acid itself is not stable and is easily decomposed by conditions such as temperature, humidity, and solvents, which brings many obstacles to production and clinical application.

[0003] The heterogeneous liquid dispersion system formed by mixing two immiscible liquids, in which one phase of liquid is dispersed in the other phase of liquid in the form of droplets, is called an emulsion. The absorption of highly lipid-soluble drugs can be significantly improved after being prepared into emulsions, thereby improving the bioavailability of the drugs. Garcinia acid is extremely lipophilic, with a LogP of up to 7.24, and has good solubility in a variety of oil phases. Therefore, it is possible to consider dissolving Garcinia acid in an oil phase to prepare an emulsion to improve its oral bioavailability and improve the efficacy.

[0004] Pickering emulsion is a new type of emulsion that uses nanometer or micrometer solid particles to replace traditional organic surfactants to stabilize the emulsion system. Unlike traditional surfactants, solid particles mainly rely on their adsorption at the oil-water interface and the spatial barriers formed by the interaction between particles to stabilize the emulsion. Pickering emulsion has its unique advantages, which can greatly reduce the amount of traditional emulsifiers and save costs; the toxic effect of solid particles on the human body is far less than that of surfactants; it is environmentally friendly and has strong interface stability.

[0005] Although Pickering emulsions have high stability, they will inevitably encounter problems such as stratification, oil separation, and Oswald ripening during long-term storage. At the same time, the stability of gambogic acid is also poor under various environmental conditions.

[0006] Therefore, the present application designs to prepare the gambogic acid into an O / W Pickering emulsion, and solidifies it into a dry emulsion to overcome the above-mentioned defects. Summary of the invention

[0007] The purpose of the present invention is to provide a garcinia acid freeze-dried emulsion and a preparation method and application thereof.

[0008] In order to achieve the above object, the present invention adopts the following technical solutions:

[0009] A lyophilized emulsion of garcinia acid, which is prepared from garcinia acid, an oil phase, chitosan, water, glacial acetic acid, sodium hydroxide and a lyophilization protective agent;

[0010] The oil phase is selected from medium chain triglycerides, castor oil, soybean oil or monolinolein;

[0011] The lyophilization protective agent is selected from mannitol, lactose, maltodextrin, trehalose, sucrose and glucose.

[0012] Furthermore, the oil phase is medium chain triglyceride, and the freeze-drying protective agent is maltodextrin.

[0013] The preparation method of the above-mentioned garcinia acid freeze-dried emulsion comprises the following steps:

[0014] Step 1, dissolving chitosan in glacial acetic acid solution to obtain a chitosan solution;

[0015] Step 2, adjusting the pH of the chitosan solution as the aqueous phase of the emulsion;

[0016] Step 3, dissolving gambogic acid in the oil phase to obtain a gambogic acid oil solution;

[0017] Step 4, adding the gambogic acid oil solution to the aqueous phase of the emulsion, preparing a crude emulsion by high-speed shearing, and homogenizing the crude emulsion by microfluidization to obtain a gambogic acid Pickering emulsion;

[0018] Step 5, adding a lyophilization protective agent to the garcinia acid Pickering emulsion, and freeze-drying to obtain a garcinia acid lyophilized emulsion.

[0019] Furthermore, the mass percentage concentration of the chitosan solution in step 1 is 0.1% to 2%.

[0020] Furthermore, in step 2, the pH of the chitosan solution is adjusted to 6.0-7.0.

[0021] Furthermore, in step 4, the high-speed shearing speed is 2000-20000 rpm, the shearing time is 2-10 minutes, the homogenizing pressure is 5000-25000 psi, and the homogenizing times are 1-10 times.

[0022] Furthermore, in the gambogic acid Pickering emulsion, the mass percentage concentration of gambogic acid is 0.1% to 5%, the volume percentage concentration of the oil phase is 5% to 50%, and the mass percentage concentration of chitosan is 0.05% to 2%.

[0023] Furthermore, in step 5, the usage ratio of the garcinia acid Pickering emulsion and the lyophilization protective agent is 100 mL: 5-30 g.

[0024] Application of the above-mentioned garcinia acid freeze-dried emulsion in the preparation of garcinia acid oral preparations.

[0025] Application of the above-mentioned garcinia acid freeze-dried emulsion in the preparation of tumor treatment drugs.

[0026] The invention deprotonates the amino groups of chitosan by adjusting pH, reduces the surface charge, shrinks the molecular chains, and self-aggregates into nanoparticles. The nanoparticles can be quickly adsorbed on the oil-water interface to emulsify the oil phase loaded with gambogic acid into a Pickering emulsion.

[0027] Compared with the existing oral carrier system for delivering garcinia acid, the advantages of the present invention are:

[0028] (1) The Pickering freeze-dried emulsion of garcinia acid prepared by the present invention solves the problem of poor water solubility of garcinia acid and improves the solubility of the drug. Through the drug release characteristics of the Pickering emulsion, it can reduce the toxic and side effects on normal tissues, improve oral bioavailability, and improve drug efficacy.

[0029] (2) Chitosan is a widely available, low-cost, safe and non-toxic linear polysaccharide, and its biocompatibility and degradability are far superior to traditional surfactants. The preparation of chitosan self-aggregated nanoparticles that stabilize Pickering emulsions only requires adjusting the pH, which is a green process and simple to operate.

[0030] (3) Freeze-dried emulsion is a good preparation form. It retains the advantages of emulsion and removes the water in the emulsion, improves stability, and facilitates transportation and storage. Freeze-dried Pickering emulsion can also be prepared into solid dosage forms such as granules, hard capsules or tablets. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 is a particle size distribution diagram of the freeze-dried Pickering emulsion of garcinia acid after reconstitution in Example 1;

[0032] Figure 2 This is a microstructure diagram of the freeze-dried Pickering emulsion of garcinia acid after reconstitution in Example 1;

[0033] Figure 3 This is the release curve of the lyophilized Pickering emulsion of garcinia acid in Example 1 in the release medium. DETAILED DESCRIPTION

[0034] Since the water solubility of gambogic acid is extremely low, its oral absorption is poor and its bioavailability is low; however, the lipophilicity of gambogic acid is strong, so the present invention is designed to dissolve it into the oil phase and develop it into a Pickering emulsion. Although the Pickering emulsion has high stability, it will inevitably encounter problems such as stratification, oil separation, and Oswald ripening during long-term storage. At the same time, the stability of gambogic acid is not good under various environmental conditions. Therefore, the present invention further designs a freeze-drying method to enhance the stability of the Pickering emulsion.

[0035] After preliminary exploration and experiments, it was found that the solubility of garcinia acid in medium-chain triglycerides is relatively high. The Pickering emulsion prepared with medium-chain triglycerides as the oil phase has good appearance and small particle size. At the same time, medium-chain triglycerides have good stability and low viscosity, so medium-chain triglycerides were selected as the oil phase.

[0036] At the same time, chitosan is a linear polysaccharide with wide sources, low price, safety and non-toxicity, good biocompatibility and degradability, and the preparation of self-aggregated nanoparticles that stabilize Pickering emulsions only requires adjusting the pH of the chitosan solution, which is a green process and simple to operate. Therefore, chitosan was selected as the solid particle to stabilize the Pickering emulsion.

[0037] The formulation process of Garcinia acid Pickering emulsion is explored as follows:

[0038] 1. Screening of oil phase types

[0039] 1.1 Drug loading

[0040] Measure 1 mL of each of medium-chain triglycerides, soybean oil, castor oil, and monolinoleylglycerol in the oil phase into a centrifuge tube, add a quantitative amount of the gambogic acid API at room temperature (25°C), and place the tube on a test tube rotary mixer to continue mixing. Observe the dissolution of gambogic acid in each oil phase. If the solution is clear and transparent, continue to add a quantitative amount of the gambogic acid API and repeat the above operation.

[0041] The results are shown in Table 1.

[0042] 1.2 Milk-forming ability

[0043] (1) Prepare 18 mL of 0.75% (w / v) glacial acetic acid solution. Under stirring at room temperature, weigh 90 mg of chitosan powder and add it to the glacial acetic acid solution to prepare a chitosan solution with a concentration of 0.5% (w / v). The mass ratio of chitosan to glacial acetic acid is 2:3. Stir continuously at room temperature to completely hydrate and dissolve the chitosan. Then, vacuum filter the chitosan solution to remove insoluble impurities.

[0044] (2) The pH value of the chitosan solution was adjusted to 6.6 with sodium hydroxide solution to prepare an aqueous phase containing self-aggregated chitosan nanoparticles.

[0045] (3) Take 18 mL of the aqueous phase obtained in step (2), add 2 mL of medium chain triglyceride, soybean oil, castor oil, and monolinoleyl glyceride respectively. Mix the oil phase and the aqueous phase uniformly by high-speed shearing to prepare a crude emulsion, the high-speed shearing speed is 10,000 rpm, and the shearing time is 5 min; put the crude emulsion into a microfluidizer for homogenization, the homogenization pressure is 15,000 rpm, and the homogenization times are 5 times to obtain a Pickering emulsion stabilized by self-aggregated chitosan nanoparticles.

[0046] Observe the appearance of Pickering emulsions prepared with different types of oil phases, including color, odor, fluidity, etc. Take 0.1 mL of the emulsion and dilute it 1000 times with purified water, then use a nanoparticle size analyzer dynamic light scattering to measure its particle size.

[0047] The results are shown in Table 1.

[0048] Table 1 Drug loading and emulsification capacity of different types of oil phases

[0049]

[0050] As shown in Table 1, medium chain triglycerides have a high drug loading capacity, good emulsion appearance and a relatively small average particle size, so medium chain triglycerides are selected as the oil phase of the Pickering emulsion.

[0051] 2. pH of chitosan solution

[0052] Prepare multiple 18 mL portions of 0.5% chitosan solution according to the method in 1.2, and adjust the solution pH to 6.0, 6.6, 6.7, 6.8, 6.9, and 7.0 with sodium hydroxide solution. Add 2 mL of medium-chain triglycerides and prepare Pickering emulsion according to the process in 1.2. Take 0.1 mL of the emulsion and dilute it 1000 times with purified water, and then use a nanoparticle size analyzer dynamic light scattering to measure its particle size.

[0053] Table 2 Particle size of emulsions prepared with different chitosan solution pH

[0054] Chitosan solution pH Average particle size (nm) 6.0 988.78 6.6 842.08 6.7 838.25 6.8 748.67 6.9 786.14 7.0 /

[0055] It can be seen from Table 2 that when the pH of the chitosan solution reaches 6.8, the emulsion particle size has a minimum value, so the optimal pH of the chitosan solution is 6.8.

[0056] 3. Chitosan solution concentration

[0057] Prepare 18 mL of chitosan solution with chitosan concentrations of 0.3%, 0.4%, 0.5%, 0.6%, and 0.7% according to the method under 1.2, and adjust the solution pH to 6.8 with sodium hydroxide solution. Add 2 mL of medium-chain triglycerides and prepare Pickering emulsion according to the process under 1.2. Take 0.1 mL of the emulsion and dilute it 1000 times with purified water, and then use a nanoparticle size analyzer dynamic light scattering to measure its particle size.

[0058] Table 3 Particle size of emulsions prepared with chitosan solutions of different concentrations

[0059] Chitosan solution concentration (%) Average particle size (nm) 0.3 1193.61 0.4 882.81 0.5 748.67 0.6 748.63 0.7 749.50

[0060] It can be seen from Table 3 that when the chitosan concentration is 0.5%, the emulsion particle size reaches the minimum value, so the optimal chitosan concentration is 0.5%.

[0061] 4. Process screening

[0062] 4.1 High speed shearing speed

[0063] Prepare 18mL of 0.5% chitosan solution according to the method under 1.2, and adjust the solution pH to 6.8 with sodium hydroxide solution. Add 2mL of medium-chain triglyceride, and prepare Pickering emulsion according to the process under 1.2, setting the high-speed shear time to 5min, the microfluidization pressure to 15,000psi, the homogenization times to 5 times, and the high-speed shear speeds to 5,000rpm, 10,000rpm, and 15,000rpm, respectively. Take 0.1mL of the emulsion and dilute it 1000 times with purified water, and then use the nanoparticle size analyzer dynamic light scattering to measure its particle size.

[0064] 4.2 High-speed shearing time

[0065] Prepare 18mL of 0.5% chitosan solution according to the method under 1.2, and adjust the solution pH to 6.8 with sodium hydroxide solution. Add 2mL of medium-chain triglyceride, prepare Pickering emulsion according to the process under 1.2, set the high-speed shear speed to 10,000rpm, the microfluidization homogenization pressure to 15,000psi, the homogenization times to 5 times, and the high-speed shear time to 2min, 5min, 8min, and 10min respectively. Take 0.1mL of emulsion and dilute it 1000 times with purified water, and then use nanoparticle size analyzer dynamic light scattering to measure its particle size.

[0066] 4.3 Microfluidization homogenization pressure

[0067] Prepare 18mL of 0.5% chitosan solution according to the method under 1.2, and adjust the solution pH to 6.8 with sodium hydroxide solution. Add 2mL of medium-chain triglyceride, and prepare Pickering emulsion according to the process under 1.2, set the high-speed shear speed to 10,000rpm, the high-speed shear time to 8min, the microfluidizer homogenization times to 5 times, and the homogenization pressures to 10,000psi, 15,000psi, and 20,000psi, respectively. Take 0.1mL of the emulsion and dilute it 1000 times with purified water, and then use the nanoparticle size analyzer dynamic light scattering to measure its particle size.

[0068] 4.4 Microfluidization homogenization times

[0069] Prepare 18mL of 0.5% chitosan solution according to the method under 1.2, and adjust the solution pH to 6.8 with sodium hydroxide solution. Add 2mL of medium-chain triglyceride, and prepare Pickering emulsion according to the process under 1.2, set the high-speed shear speed to 10,000rpm, the high-speed shear time to 8min, the microfluidization homogenization pressure to 15,000psi, and the homogenization times to 2 times, 5 times, and 8 times, respectively. Take 0.1mL of the emulsion and dilute it 1000 times with purified water, and then use the nanoparticle size analyzer dynamic light scattering to measure its particle size.

[0070] Table 4 Particle size of emulsions prepared under different process conditions

[0071]

[0072] According to the data in Table 4, the high-speed shear speed for preparing the Pickering emulsion was determined to be 10,000 rpm, the high-speed shear time was 8 min, the microfluidization homogenization pressure was 15,000 psi, and the number of times was 5 times.

[0073] The present invention is further described in detail below in conjunction with the accompanying drawings and specific examples, but it should not be construed as limiting the present invention. Without departing from the spirit and substance of the present invention, the modification or replacement of the method, steps or conditions of the present invention all belong to the scope of the present invention. The experimental methods and reagents without specifying the specific conditions in the examples are all in accordance with the conventional conditions in the art.

[0074] Example 1

[0075] Garcinia acid freeze-dried Pickering emulsion 1

[0076] Its composition and content are as follows:

[0077]

[0078] The preparation method of this embodiment is as follows

[0079] (1) Prepare 18 mL of 0.75% (w / v) glacial acetic acid solution, weigh 90 mg of chitosan powder and add it to the glacial acetic acid solution while stirring at room temperature to prepare a chitosan solution with a concentration of 0.5% (w / v); stir continuously at room temperature to completely hydrate and dissolve the chitosan; then vacuum filter the chitosan solution to remove insoluble impurities.

[0080] (2) The pH value of the chitosan solution was adjusted to 6.8 with sodium hydroxide solution to prepare an aqueous phase containing self-aggregated chitosan nanoparticles.

[0081] (3) Accurately weigh 400 mg of gambogic acid into 2 mL of oil phase medium chain triglyceride and stir at room temperature until the gambogic acid is completely dissolved to form a clear single-phase solution, thereby obtaining a 200 mg / mL gambogic acid oil solution.

[0082] (4) Take 18 mL of the aqueous phase obtained in step (2), add 2 mL of the oil phase loaded with gambogic acid. Mix the oil phase and the aqueous phase uniformly by high-speed shearing to prepare a crude emulsion, the high-speed shearing speed is 10000 rpm, and the shearing time is 8 min; put the crude emulsion into a microfluidizer for homogenization, the homogenization pressure is 15000 rpm, the number of times is 5, and the Pickering emulsion stabilized by self-aggregated chitosan nanoparticles is obtained.

[0083] (5) Weigh 20% (w / v) maltodextrin into the gambogic acid Pickering emulsion obtained in step (4), place it in a freeze dryer cold trap for pre-freezing, and then freeze-dry for 24 hours to completely remove moisture, thereby obtaining a gambogic acid freeze-dried Pickering emulsion.

[0084] Example 2

[0085] Garcinia acid freeze-dried Pickering emulsion 2

[0086] Its composition and content are as follows:

[0087]

[0088] The preparation method of this embodiment is the same as that of embodiment 1.

[0089] Example 3

[0090] Garcinia acid freeze-dried Pickering emulsion 3

[0091] Its composition and content are as follows:

[0092]

[0093] The preparation method of this embodiment is the same as that of embodiment 1.

[0094] Test Example 1

[0095] The samples of the freeze-dried Pickering emulsion of garcinia acid prepared in Examples 1 to 3 were evaluated, and the evaluation indexes were appearance, redispersibility, and particle size change rate. The evaluation criteria were as follows:

[0096] ① Appearance: No collapse, no shrinkage, no sticking to the wall, can be removed in one piece, uniform color, no spots, fine texture is preferred.

[0097] ② Redispersibility: Take an appropriate amount of the freeze-dried Pickering emulsion of each example, add water as required, and shake to disperse. If the emulsion can be quickly dispersed after shaking, the redispersibility is good; if multiple shaking, ultrasound, or vortexing is required, the redispersibility is poor.

[0098] ③ Particle size change rate: Take an appropriate amount of the freeze-dried Pickering emulsion of each example, add water as required, shake and disperse, measure its particle size d1 by dynamic light scattering, compare it with the particle size d0 of the emulsion before freeze drying, and calculate the particle size change rate (%) according to the formula:

[0099]

[0100] The results are shown in the table below:

[0101] Table 5 Freeze-dried emulsions prepared with different freeze-dried protective agents

[0102] name Appearance Redispersibility Particle size change rate (%) Mannitol White loose powder Poor 255.12 lactose Spotted, partially adherent good 106.9 Maltodextrin Yellow loose powder good 99.70

[0103] From the above results, it can be seen that when maltodextrin is selected as the freeze-drying protective agent, the appearance, redispersibility and particle size change rate of the freeze-dried Pickering emulsion of garcinia acid are relatively good.

[0104] Test Example 2

[0105] Take 0.2 g of the lyophilized Pickering emulsion of garcinia acid prepared in Example 1, add 1 mL of purified water, hydrate and shake to restore to an emulsion, dilute 1000 times with purified water, and use a nanoparticle size analyzer to measure its particle size and polydispersity index by dynamic light scattering. The particle size is 336.21±3.15 nm, and the polydispersity index is 0.115±0.022; the Zeta potential is measured by electrophoretic light scattering, and the Zeta potential is 35.37±0.95 mV. Figure 1 shown.

[0106] Take 0.2 g of the lyophilized Pickering emulsion of garcinia acid prepared in Example 1, add 1 mL of purified water, hydrate and shake to restore it into an emulsion, dilute it 10 times with purified water and observe its morphology under a microscope. Figure 2 As shown, the morphology of the reconstituted emulsion is good.

[0107] Test Example 3

[0108] In vitro release assay

[0109] The in vitro release behavior of the lyophilized Pickering emulsion of garcinia acid prepared in Example 1 in simulated intestinal fluid was investigated by direct drug release method. 0.5 g of the lyophilized Pickering emulsion of garcinia acid prepared in Example 1 was accurately weighed and directly put into 100 mL of PBS (pH 6.8) release medium containing 0.5% (w / v) Tween 20, sealed and placed in a constant temperature air bath oscillator (37°C, 100 rpm), and a blank release medium was placed at the same time for rehydration. 0.25h, 0.5h, 1h, 2h, 2.5h, and 4h after the start of the in vitro release experiment, 1 mL of solution was taken from the beaker, filtered through a 0.22μm water filter membrane, and the subsequent filtrate was taken as the test solution. Immediately supplement the release medium of the same volume and temperature to maintain the total volume unchanged. The test solution was detected and analyzed by HPLC, and the in vitro release curve was drawn with time as the horizontal axis and the cumulative release degree as the vertical axis.

[0110]

[0111] C1, C2, ..., C n : The concentration of the test sample in the 1st, 2nd, …, nth sampling;

[0112] V0, V: initial volume of release medium and sampling volume;

[0113] W: total dosage.

[0114] The results are as follows Figure 3 As shown in the figure, the drug can diffuse from the oil phase into the release medium faster, and the release rate is faster; after 4 hours, the gambogic acid in the Pickering emulsion is almost completely released.

[0115] Test Example 4

[0116] Stability test

[0117] The lyophilized Pickering emulsion of garcinia acid prepared in Example 1 was stored at room temperature (25°C) and 4°C for three months. The appearance, redispersibility and particle size change rate of the lyophilized Pickering emulsion at 0, 1, 2 and 3 months were observed, and no significant differences were found. The drug content was further determined by high performance liquid chromatography, and it was found that there was almost no change, so the lyophilized Pickering emulsion of garcinia acid had good stability.

[0118] Table 6 Stability test results of lyophilized Pickering emulsion of garcinia acid

[0119]

[0120] From the above results, it can be seen that the freeze-dried Pickering emulsion preparation of garcinia acid prepared by the present invention has good stability.

Claims

1. A lyophilized emulsion of garcinia acid, characterized in that: It is made of gambogic acid, oil phase medium chain triglyceride, chitosan, water, glacial acetic acid, sodium hydroxide and maltodextrin, wherein the amounts of gambogic acid, oil phase medium chain triglyceride, chitosan, water and maltodextrin are as follows: Garcinia acid 400mg Medium Chain Glycerides 2mL Chitosan 90mg Water 18mL Maltodextrin 4g; The preparation method of the freeze-dried emulsion comprises the following steps: Step 1, prepare 18 mL of 0.75% w / v glacial acetic acid solution, weigh 90 mg of chitosan powder and add it to the glacial acetic acid solution under stirring at room temperature to prepare a chitosan solution with a concentration of 0.5% w / v, stir continuously at room temperature to completely hydrate and dissolve the chitosan, and then vacuum filter the chitosan solution to remove insoluble impurities; Step 2, adjusting the pH of the chitosan solution to 6.8 with a sodium hydroxide solution to prepare an aqueous phase containing self-aggregated chitosan nanoparticles; Step 3, accurately weigh 400 mg of gambogic acid into 2 mL of oil phase medium chain triglyceride, and stir at room temperature until the gambogic acid is completely dissolved to form a clear single-phase solution, to obtain a 200 mg / mL gambogic acid oil solution; Step 4, take 18 mL of the aqueous phase obtained in step 2, add 2 mL of the oil phase loaded with gambogic acid, mix the oil phase and the aqueous phase uniformly by high-speed shearing to prepare a crude emulsion, the high-speed shear speed is 10000 rpm, the shearing time is 8 min, and the crude emulsion is placed in a microfluidizer for homogenization at a homogenization pressure of 15000 rpm for 5 times to obtain a Pickering emulsion stabilized by self-aggregated chitosan nanoparticles; Step 5, weigh 20% w / v maltodextrin into the gambogic acid Pickering emulsion obtained in step 4, place it in a freeze dryer cold trap for pre-freezing, and then freeze-dry for 24 hours to completely remove moisture to obtain a freeze-dried gambogic acid Pickering emulsion.

Images