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Method for preparing shrapnel type anti-tumor gold nano conjugate heterozygous liposome and application thereof

A technology of conjugates and gold nanometers, applied in the field of biomedical technology and nanotechnology, can solve the problems of reduced drug efficacy, poor water solubility, and increased side effects

Inactive Publication Date: 2015-11-11
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the current research results show that the common shortcomings of this type of drug delivery system are: (1) poor water solubility; (2) lack of trigger linking groups between the drug and the nanoparticles to achieve drug release; (3) the drug is still exposed to On the outer surface of the system, after entering the body, there will inevitably be specific or non-specific adsorption, recognition and enzymatic hydrolysis, which will reduce the efficacy of the drug and increase the side effects

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  • Method for preparing shrapnel type anti-tumor gold nano conjugate heterozygous liposome and application thereof
  • Method for preparing shrapnel type anti-tumor gold nano conjugate heterozygous liposome and application thereof
  • Method for preparing shrapnel type anti-tumor gold nano conjugate heterozygous liposome and application thereof

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preparation example Construction

[0036] The invention relates to the design and construction of a novel gold nanoparticle paclitaxel conjugate liposome, a preparation method, in vitro characterization of the drug, and research on pharmacozoological properties. Preparation methods of conjugates, drug release characteristics in vitro, and drug delivery applications. The preparation of the gold nano-paclitaxel conjugate in the present invention includes: (1) preparation of the core of the gold nano-particle; (2) synthesis of paclitaxel sulfhydrylated biocompatibility ligand; (3) preparation of the gold nano-paclitaxel conjugate.

[0037] The gold nano-paclitaxel conjugate liposome prepared by the present invention packs the gold conjugate into the liposome, wherein the gold conjugate uses gold nanoparticles as the core, thiolated PEG as the linking arm, and paclitaxel as the loaded drug. The lipid material is prepared by mixing lecithin and cholesterol at a ratio of 4:1. The size of the gold nano-paclitaxel con...

Embodiment 1

[0038] Example 1 Preparation of "Small Bullets" Paclitaxel-Gold Nanoconjugate Hybrid Liposomes

[0039] 1. Synthesis of gold nanoparticles:

[0040] The glass instruments used were washed successively with aqua regia, distilled water, and filtered water, and a solution of chloroauric acid (0.020 mg / mL) and trisodium citrate (2.004 mg / mL) was prepared with filtered water, and in an ice-water bath (0°C), Add 0.615mL of chloroauric acid mother liquor into the above-mentioned 24.385mL trisodium citrate solution, and under vigorous stirring, add the frozen sodium borohydride solution (0.04mg / mL, 25mL) dropwise in the mixture solution, and the reaction solution becomes From orange to purple red, keep the reaction temperature at 0°C, continue to stir vigorously for 15-20 minutes until the color no longer changes, store at 4°C, and prepare gold nanoparticles with a size of 2-5nm overnight.

[0041] 2. Preparation of paclitaxel-gold nanoconjugates:

[0042] Accurately weigh the side ...

Embodiment 2

[0046] Embodiment 2 Characterization of paclitaxel-gold nanoconjugate hybrid liposome

[0047] 1. Transmission Electron Microscopy

[0048] Take the prepared paclitaxel gold nanoconjugate, paclitaxel liposome, paclitaxel gold nanoconjugate liposome and paclitaxel / paclitaxel gold nanoconjugate liposome solution samples, dilute to a suitable concentration, drop onto the copper grid, wait The solvent was evaporated on the copper grid, and the particle morphology and size were characterized by transmission electron microscopy.

[0049] 2. UV-Vis absorption spectrum

[0050] Take the prepared paclitaxel gold nanoconjugate, paclitaxel liposome, paclitaxel gold nanoconjugate liposome and paclitaxel / paclitaxel gold nanoconjugate liposome solution samples, dilute to an appropriate concentration, and place the sample in a UV-visible spectrometer In the cell, scanning is performed in the range of 200-800nm.

[0051] 3. Thermogravimetric analysis

[0052] Thermogravimetric analysis wa...

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Abstract

The invention belongs to the field of biomedical technologies and nano science and technologies, and particularly relates to a method for preparing novel 'shrapnel' type anti-tumor gold nano conjugate heterozygous liposome and application thereof. Liposome is used as a shell of the heterozygous liposome. The method includes individually preparing medicine liposome and medicine-gold nano particle conjugate liposome; preparing the 'shrapnel' type anti-tumor gold nano conjugate heterozygous liposome by two hybrid steps or a one-step process implemented by the aid of jointly entrapped medicine and medicine-gold nano conjugates. The method and the application have the advantages that the entrapped medicine can have initial release and sustained-release functions, accordingly, the half life of the medicine can be prolonged, the bioavailability of the medicine and medicine metabolism dynamic properties can be improved, the medicine has long-circulation solubility, anti-tumor treatment effects of the medicine can be improved, and the 'shrapnel' type anti-tumor gold nano conjugate heterozygous liposome can be used for intravenous injection tumor diagnosis and treatment research.

Description

technical field [0001] The invention belongs to the fields of biomedical technology and nanotechnology, and specifically relates to the design, construction and application of a novel gold nanoparticle-chemotherapy drug conjugate hybrid liposome. The system combines the concepts of nano-drug carriers and nano-prodrugs, in which the liposome nano-sized carrier acts as a delivery system and protects the drug; the gold nanoparticle-chemotherapy drug conjugate is equivalent to the nano-prodrug of paclitaxel drug, It is the nanometerization and integration of chemotherapy drugs, entrapped in the liposome bilayer, and plays the role of increasing drug concentration per unit volume, cell uptake and selective release. The combination of the two can improve the bioavailability and pharmacokinetic properties of the drug, endow the drug with good solubility, long circulation and liver targeting properties, and can be used for intravenous injection of tumor diagnosis and treatment researc...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/04A61K47/24A61K47/48A61K31/337A61P35/00
Inventor 丁娅张灿张宁张文婕刘爱贇
Owner CHINA PHARM UNIV
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