A leukocyte membrane-modified paclitaxel targeted sustained-release liposome and preparation method thereof

Abstract

The invention discloses a paclitaxel-targeted sustained-release liposome modified by a leukocyte membrane and a preparation method thereof, and belongs to the technical fields of drug control releaseand biomaterials. The paclitaxel-targeted sustained-release liposome comprises a drug-loaded sustained-release liposome and the leukocyte membrane modifying the surface of the drug-loaded sustained-release liposome, wherein the drug-loaded sustained-release liposome is composed of paclitaxel, star-shaped cholic acid functionalized polylactic acid, soybean phospholipid and cholesterol. The star-shaped cholic acid functionalized polylactic acid with excellent biocompatibility is introduced into the paclitaxel sustained-release liposome, surface modification is performed by the leukocyte membrane, the prepared paclitaxel-targeted sustained-release liposome overcomes the toxic and side effects caused by a surfactant polyoxyethylene castor oil in a conventional paclitaxel injection liquid, andhas the advantages of excellent sustained-release effect, good tumor targeting property, long half-life period in vivo, high stability and good biocompatibility.

Description

technical field

[0001] The invention belongs to the technical field of drug controlled release and biomaterials, and in particular relates to a leukocyte membrane-modified paclitaxel targeted slow-release liposome and a preparation method thereof. Background technique

[0002] Paclitaxel is a diterpene compound extracted from Taxus genus Taxus, which has a unique anti-tumor effect. It can form stable microtubule bundles after combining with tubulin, inhibit the replication of cancer cells, and thus prevent cancer cells from Proliferation is a broad-spectrum and highly effective anticancer drug, mainly used for the treatment of ovarian cancer, breast cancer, melanoma, lung cancer, colorectal cancer, head and neck cancer, lymphoma, brain tumor and other cancers.

[0003] However, due to the special physical and chemical properties and pharmacological effects of paclitaxel, there are still some shortcomings in clinical use, such as unsatisfactory curative effect and obvious tox...

Examples

Embodiment 1

[0022] 1. A method for preparing leukocyte membrane-modified paclitaxel-targeted sustained-release liposomes, the method comprising the following steps:

[0023] (1) Preparation of paclitaxel sustained-release liposomes: Weigh 5 mg of paclitaxel, 65 mg of soybean lecithin, 16 mg of cholesterol and 10 mg of star-shaped cholic acid-functionalized polylactic acid, dissolve them in a certain amount of chloroform, and evaporate under reduced pressure at 37°C Remove the solvent until a layer of liposome film is formed on the inner wall of the eggplant-shaped bottle, put it in a vacuum desiccator for 24 hours, add phosphate buffer (pH7.4), hydrate in a constant temperature water bath at 40°C for 1 hour, and ultrasonicate with an ice bath probe for 4-6 minutes , processed by a micro-jet high-pressure homogenizer (homogenization pressure is 120 MPa, homogenization temperature is 37° C., homogenization times is 5 times), and crosses a 0.22 μm microporous membrane to obtain paclitaxel sus...

Embodiment 2

[0053] 1. A method for preparing leukocyte membrane-modified paclitaxel-targeted sustained-release liposomes, the method comprising the following steps:

[0054] The preparation method is the same as in Example 1, wherein the dosage of each component is: 7.5 mg of paclitaxel, 60 mg of soybean lecithin, 20 mg of cholesterol, 7.5 mg of star-shaped cholic acid functionalized polylactic acid, and 5 mg of leukocyte membrane.

[0055] 2. Pharmacological characterization of paclitaxel-targeted sustained-release liposomes

[0056] (1), particle size and polydispersity coefficient: adopt laser scattering particle size distribution analyzer to measure size, measurement result: average particle diameter is 87.5nm; Polydispersity coefficient is 0.186.

[0057] (2), surface topography: the measuring method is the same as that in Example 1, and the measurement result: the surface topography is spherical, and the size distribution is comparatively uniform.

[0058] (3), measurement and resu...

Embodiment 3

[0077] 1. A method for preparing leukocyte membrane-modified paclitaxel-targeted sustained-release liposomes, the method comprising the following steps:

[0078] The preparation method is the same as in Example 1, wherein the dosage of each component is: 10 mg of paclitaxel, 55 mg of soybean lecithin, 24 mg of cholesterol, 8 mg of star-shaped cholic acid functionalized polylactic acid, and 3 mg of white blood cell membrane.

[0079] 2. Pharmacological characterization of paclitaxel-targeted sustained-release liposomes

[0080] (1), particle size and polydispersity coefficient: adopt laser scattering particle size distribution analyzer to measure size. Measurement results: the average particle size is 84.9nm; the polydispersity coefficient is 0.177;

[0081] (2), surface topography: the measuring method is the same as that in Example 1, and the measurement result: the surface topography is spherical, and the size distribution is comparatively uniform.

[0082] (3), measuremen...

technical field

[0001] The invention belongs to the technical field of drug controlled release and biomaterials, and in particular relates to a leukocyte membrane-modified paclitaxel targeted slow-release liposome and a preparation method thereof. Background technique

[0002] Paclitaxel is a diterpene compound extracted from Taxus genus Taxus, which has a unique anti-tumor effect. It can form stable microtubule bundles after combining with tubulin, inhibit the replication of cancer cells, and thus prevent cancer cells from Proliferation is a broad-spectrum and highly effective anticancer drug, mainly used for the treatment of ovarian cancer, breast cancer, melanoma, lung cancer, colorectal cancer, head and neck cancer, lymphoma, brain tumor and other cancers.

[0003] However, due to the special physical and chemical properties and pharmacological effects of paclitaxel, there are still some shortcomings in clinical use, such as unsatisfactory curative effect and obvious tox...

Examples

Embodiment 1

[0022] 1. A method for preparing leukocyte membrane-modified paclitaxel-targeted sustained-release liposomes, the method comprising the following steps:

[0023] (1) Preparation of paclitaxel sustained-release liposomes: Weigh 5 mg of paclitaxel, 65 mg of soybean lecithin, 16 mg of cholesterol and 10 mg of star-shaped cholic acid-functionalized polylactic acid, dissolve them in a certain amount of chloroform, and evaporate under reduced pressure at 37°C Remove the solvent until a layer of liposome film is formed on the inner wall of the eggplant-shaped bottle, put it in a vacuum desiccator for 24 hours, add phosphate buffer (pH7.4), hydrate in a constant temperature water bath at 40°C for 1 hour, and ultrasonicate with an ice bath probe for 4-6 minutes , processed by a micro-jet high-pressure homogenizer (homogenization pressure is 120 MPa, homogenization temperature is 37° C., homogenization times is 5 times), and crosses a 0.22 μm microporous membrane to obtain paclitaxel sus...

Embodiment 2

[0053] 1. A method for preparing leukocyte membrane-modified paclitaxel-targeted sustained-release liposomes, the method comprising the following steps:

[0054] The preparation method is the same as in Example 1, wherein the dosage of each component is: 7.5 mg of paclitaxel, 60 mg of soybean lecithin, 20 mg of cholesterol, 7.5 mg of star-shaped cholic acid functionalized polylactic acid, and 5 mg of leukocyte membrane.

[0055] 2. Pharmacological characterization of paclitaxel-targeted sustained-release liposomes

[0056] (1), particle size and polydispersity coefficient: adopt laser scattering particle size distribution analyzer to measure size, measurement result: average particle diameter is 87.5nm; Polydispersity coefficient is 0.186.

[0057] (2), surface topography: the measuring method is the same as that in Example 1, and the measurement result: the surface topography is spherical, and the size distribution is comparatively uniform.

[0058] (3), measurement and resu...

Embodiment 3

[0077] 1. A method for preparing leukocyte membrane-modified paclitaxel-targeted sustained-release liposomes, the method comprising the following steps:

[0078] The preparation method is the same as in Example 1, wherein the dosage of each component is: 10 mg of paclitaxel, 55 mg of soybean lecithin, 24 mg of cholesterol, 8 mg of star-shaped cholic acid functionalized polylactic acid, and 3 mg of white blood cell membrane.

[0079] 2. Pharmacological characterization of paclitaxel-targeted sustained-release liposomes

[0080] (1), particle size and polydispersity coefficient: adopt laser scattering particle size distribution analyzer to measure size. Measurement results: the average particle size is 84.9nm; the polydispersity coefficient is 0.177;

[0081] (2), surface topography: the measuring method is the same as that in Example 1, and the measurement result: the surface topography is spherical, and the size distribution is comparatively uniform.

[0082] (3), measuremen...

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