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PH-sensitive precursor cation nanometer liposome of target tumour cell and preparation method thereof

A technology of nanoliposomes and tumor cells, which is applied in the field of nanoliposomes targeting tumor cells and its preparation, which can solve problems such as difficult degradation, hinder liposome fusion, toxicity, etc., achieve low cost and improve utilization rate , The effect of simple preparation process

Inactive Publication Date: 2010-07-07
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, the traditional use of PEG-modified long-circulating liposomes such as polyethylene glycol-distearoylphosphatidylphosphatidylethanolamine (PEG-DSPE) liposomes, polyethylene glycol-phosphatidylethanolamine (PEG-PE) lipids Plastids and polyethylene glycol-cholesterol (PEG-CHOL) are not easy to degrade in vivo, which may hinder the fusion of liposomes and tumor cells when they reach the tumor site because PEG is still attached to the surface of liposomes
Although cationic liposomes (such as liposomes containing amino compounds and chitosan-modified liposomes) can greatly increase the fusion speed with cells in vitro, they will first interact with negatively charged cells in the blood after intravenous injection. cell fusion, causing toxicity

Method used

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  • PH-sensitive precursor cation nanometer liposome of target tumour cell and preparation method thereof
  • PH-sensitive precursor cation nanometer liposome of target tumour cell and preparation method thereof
  • PH-sensitive precursor cation nanometer liposome of target tumour cell and preparation method thereof

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example 1

[0020] Example 1. Weigh 100 mg of egg yolk lecithin, 1 mg of octadecylamine and 4 mg of drug hydroxycamptothecin, dissolve in 20 ml of absolute ethanol (adjust the pH to 5.5 with glacial acetic acid), and transfer to a 500 ml eggplant-shaped bottle for a 40°C constant temperature water bath Rotary evaporator distills off the organic solvent under reduced pressure, and forms a uniform transparent lipid film on the bottle wall, hydrates the lipid film with 10ml of 40°C deionized water to form a slightly yellow suspension, and passes through a high-pressure homogenizer under a pressure of 140MPa Squeeze the emulsion through a 50nm membrane 6 times to obtain a cationic liposome solution. Preparation molecular weight 50KDa, degree of substitution is 50%, concentration is the carboxymethyl chitosan solution of 2.0%, 10ml liposome solution is slowly added dropwise in the 10ml carboxymethyl chitosan solution, and the time of dropping is 10 minutes, The stirring time at room temperatur...

example 2

[0025] Example 2. Weigh 50 mg of egg yolk lecithin, 1 mg of DC-Chol, 50 mg of cholesterol and 4 mg of drug doxorubicin, dissolve in 20 ml of absolute ethanol, transfer to a 500 ml eggplant-shaped bottle, and use a rotary evaporator to distill under reduced pressure in a 40°C constant temperature water bath Organic solvent, form a uniform transparent lipid film on the bottle wall, vacuum dry for more than 8 hours after film formation to remove the organic solvent, take 10ml of 200mmol / l ammonium sulfate solution to hydrate the lipid film for more than 2 hours, and form a blank liposome suspension After 6 times of extruding and emulsifying through a 50nm membrane with a high-pressure homogenizer at a pressure of 140MPa, dialyze with a pH7.4 phosphate buffer solution for 9h to remove ammonium sulfate in the external water phase to prepare blank liposomes. Take blank liposomes and add an equivalent amount of doxorubicin in PBS solution, and magnetically stir at a constant temperatu...

example 3

[0030] Example 3. Weigh soybean lecithin 80mg, DC-Chol 2mg, cholesterol 20mg and drug paclitaxel 4mg, dissolve in 20ml of absolute ethanol (glacial acetic acid adjusts pH to 5.5), transfer to 40 ℃ constant temperature water bath with rotation in 500ml eggplant-shaped bottle The organic solvent was distilled off under reduced pressure by an evaporator, and a uniform transparent lipid film was formed on the bottle wall. The lipid film was hydrated with 10ml of deionized water at 40°C to form a coarse suspension. After being treated with a 300W ultrasonic probe for 60 minutes, squeezed through the film The pore size is 0.22 μm, and a cationic liposome solution is obtained. Prepare molecular weight 210KDa, degree of substitution is 60%, concentration is 1.0% carboxymethyl chitosan solution, 10ml liposome solution is slowly added dropwise in 50ml carboxymethyl chitosan solution, and the time of dropping is 5 minutes, The stirring time at room temperature is 10 minutes, and the cati...

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Abstract

The invention discloses a pH-sensitive precursor cation nanometer liposome of a target tumour cell and a preparation method thereof. A product consists of a cation liposome and a hydrophilic layer of which the surface is combined through electrostatic force and is provided with negative charge and which is easy to dissolve in an acidic environment. After intravenous injection, the liposome is not fused with a cell of which the surface is provided with negative charge in blood, can be rapidly fused with the tumor cell after reaching a tumor part, and effectively releases medicament to kill the tumor cell. The liposome can effectively transport an antitumor medicament to the tumor cell, overcomes the disadvantages of the conventional liposome, improves the efficiency of the antitumor medicament of killing the tumor cell, and reduces the toxicity of the medicament.

Description

technical field [0001] The invention belongs to the field of anticancer drug dosage forms, and in particular relates to a nano liposome targeting tumor cells and a preparation method thereof. Background technique [0002] Liposome carrier is currently one of the most potential drug delivery systems in cancer treatment. After the drug is encapsulated in liposome, the drug will accumulate more in tumor tissue and reduce the toxicity to normal tissue. In addition, liposomes can also improve the solubility of drugs and improve the stability of drug structures. However, ordinary liposomes are quickly regarded as foreign substances by the Reticuloendothelial System (RES) after intravenous injection, and are taken up by macrophages and transported to liver, spleen, bone marrow, etc. Cells are toxic. Therefore, people modify the surface of liposomes to avoid the capture of RES, and enter more solid tumors with high capillary permeability and lack of lymphatic return, reduce the to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/36A61K45/00A61P35/00
Inventor 戎佩佩宋金春潘丽华
Owner WUHAN UNIV
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