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Protein medicine-carrying nano particle synthesis method

A technology of drug-loaded nano and synthetic methods, which is applied in the field of synthesis of protein drug-loaded nanoparticles, can solve the problems of increasing the production process of nano drug-loaded particles, cumbersome manufacturing process, and affecting drug load, so as to achieve improved stability and good stability , size controllable effect

Inactive Publication Date: 2013-03-06
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Usually, the size of a single protein is within a few nanometers, which is not suitable for direct drug loading.
The protein nanoparticles currently used for drug loading are usually protein complexes, so it is often necessary to add some reducing agents or cross-linking agents during the synthesis process. also increased its potential toxicity
In addition, in many current protein nano drug-loaded particles, the nanoparticle synthesis process and the drug loading process are usually completed separately, which makes the manufacturing process more cumbersome and affects the loading of drugs into the core part of the nanoparticle.

Method used

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  • Protein medicine-carrying nano particle synthesis method
  • Protein medicine-carrying nano particle synthesis method
  • Protein medicine-carrying nano particle synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] 1. Prepare a mixed solution of α-lactalbumin and doxorubicin hydrochloride

[0019] 1) Weigh 6 mg of α-lactalbumin and dissolve it in phosphate buffer (pH 7) to make protein mother solution (3 mg / ml);

[0020] 2) Weigh 1.2 mg of doxorubicin hydrochloride to make doxorubicin hydrochloride mother solution (3 mg / ml, dissolved in DMSO),

[0021] 3) Mix the protein mother liquor and doxorubicin hydrochloride mother liquor in the last two steps to prepare a mixed solution, so that the concentration of α-lactalbumin in the mixed solution is 1.5mg / ml, and the concentration of α-lactalbumin and doxorubicin hydrochloride The mass ratio is 1:0.2, and the solution is distributed into quartz cuvettes with an optical path of 1-2 mm.

[0022] 2. Ultraviolet light irradiates the mixed solution

[0023] UV light (270-310nm) irradiates the solution for 5 minutes, and the light intensity is 3mW / cm 2 . The change of protein secondary structure is characterized by its far-ultraviolet ci...

Embodiment 2

[0027] The ultraviolet irradiation time was 7 minutes, and the rest of the experimental conditions were the same as in Example 1.

[0028] The circular dichroism spectrum of the secondary structure of the protein varies by about 3%.

[0029] A pure drug-loaded nanoparticle solution was obtained, the effective particle diameter of which was about 200 nm, and the drug-loaded amount was 14.1%. The nanoparticles can maintain a stable shape within 20 days, and no obvious aggregation and precipitation are seen.

Embodiment 3

[0031] The mass ratio of α-lactalbumin to doxorubicin hydrochloride was 1:0.05, and the rest of the experimental conditions were the same as in Example 1.

[0032] The obtained pure drug-loaded nanoparticles have an effective particle size of about 79nm and a drug-loaded amount of 3.3%. The nanoparticles can maintain a stable shape within 20 days, and no obvious aggregation and precipitation are seen.

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Abstract

The invention relates to a protein medicine-carrying nano particle synthesis method. Without auxiliaries such as adding denaturant, reductant or crosslinking agent, synthesis and medicine carrying of nano particles are synchronously completed. The protein medicine-carrying nano particle synthesis method includes irradiating mixed solution of protein and hydrophobic medicines for 3-10 minutes by ultraviolet light, so that disulfide bonds in the protein are opened, variation of circular dichroism spectrum of the protein secondary structure is within 10%, a small amount of exposed protein hydrophobic base group and the hydrophobic medicines are gathered, medicine-carrying nano particles are formed at one step, protein contains tryptophan and disulfide bonds, absolute value of zeta potential on the surface of the protein is not smaller than 15mV, and the protein concentration in the mixed solution ranges from 0.5mg / ml to 5mg / ml. The synthesized nano particles are controllable in size, uniform and good in stability, and medicine carrying quantity can reach 20% maximally.

Description

technical field [0001] The invention relates to a method for synthesizing protein drug-loaded nanoparticles. Background technique [0002] The rise of nanotechnology has drawn widespread attention to drug delivery based on polymer nanoparticles. In addition to the advantages of traditional drug delivery systems such as improved drug solubility, increased drug stability, and sustained release, polymer nanoparticle drug carriers, It can also greatly change the tissue distribution and metabolism of drugs, improve drug efficacy and reduce side effects. In addition, tumors and other lesions have selective high permeability and retention (EPR effect) for macromolecular substances. When nanoparticles circulate to tumors, they can enter tumors and other lesions through this passive targeting effect. . Polymer nanoparticles can effectively prolong the circulation time of drugs in the body, and better exert the EPR effect of drug-loaded nanoparticles, so that the drug can maximize t...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K47/42A61K31/704A61P35/00
Inventor 王炜谢金兵秦猛曹毅
Owner NANJING UNIV
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