Preparation method of double-targeting acid-sensitive prussian blue drug delivery system and application thereof

A Prussian blue and acid-sensitive technology, which is applied in the field of preparation of targeted drug delivery systems, can solve problems such as drug resistance, achieve simple and mild preparation methods, improve therapeutic effects, and enhance chemotherapy effects

Active Publication Date: 2020-10-09
SOUTHEAST UNIV
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

Second, this interaction makes it acquire adhesion, migration and anti-apoptotic signals, leading to the occurrence of drug resistance

Method used

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  • Preparation method of double-targeting acid-sensitive prussian blue drug delivery system and application thereof
  • Preparation method of double-targeting acid-sensitive prussian blue drug delivery system and application thereof
  • Preparation method of double-targeting acid-sensitive prussian blue drug delivery system and application thereof

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[0031] The present invention is a preparation method of an acid-sensitive Prussian blue drug-loading system with dual-target modification of CXCR4 antagonistic polypeptide and hyaluronic acid, comprising the following steps:

[0032] The technical solution is, firstly, acid-sensitive polyethylene glycol-polyethyleneimine molecules are adsorbed on the surface of Prussian blue nanoparticles through electrostatic, hydrogen bond, etc. interactions; secondly, CXCR4 antagonistic polypeptide E5 and hyaluronic acid are chemically bonded to Prussian blue The polyethyleneimine molecules on the surface of blue nanoparticles are connected; again, daunorubicin is loaded on the surface of Prussian blue nanoparticles through hydrogen bonding ( figure 1 ).

[0033] The preparation method comprises the following steps:

[0034](1) Preparation of Prussian blue nanoparticles (PBNPs): use potassium ferricyanide as raw material, polyvinylpyrrolidone as reducing agent and stabilizer, dissolve it i...

Embodiment 1

[0049] Preparation of Prussian Blue Nanoparticles

[0050] Weigh 131.7mg of potassium ferricyanide and 3g of polyvinylpyrrolidone K30 and dissolve them in 40mL of 0.01M hydrochloric acid, and stir them magnetically to dissolve them. After the solution turns yellow and clear, place it in a water bath at 80°C for 20 hours. After the reaction was finished, the blue solution obtained was centrifuged at 10000rpm for 1 hour, the precipitate was washed once with water, twice with ethanol, and then washed once with water, and dried in vacuum at 55° C. for 24 hours. The dried Prussian blue nanoparticles ( PBNPs) were collected and placed in a 4°C refrigerator for later use.

Embodiment 2

[0052] Preparation of Acid Sensitive Polyethyleneimine-Polyethylene Glycol Modified Prussian Blue Nanoparticles

[0053] Precisely weigh a certain amount of PBNPs and polyethyleneimine-polyethylene glycol, and prepare them into an aqueous solution with a concentration of 0.5 mg / mL, and ultrasonically disperse the nanoparticles evenly. Under magnetic stirring, 30 mL of PBNPs was added dropwise into 15 mL of polyethyleneimine-polyethylene glycol solution, and stirring was continued for 0.5 hours. After stirring, excess HA was removed by ultrafiltration, and washed with pure water for 3 times. The purified polyethyleneimine-polyethylene glycol-modified Prussian blue nanoparticles (PP-PBNPs) were formulated into a 0.5 mg / mL aqueous solution and stored in a refrigerator at 4°C for use.

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Abstract

The invention discloses a preparation method of a double-targeting acid-sensitive prussian blue drug delivery system and an application thereof, which can effectively solve the problems of leukemia drug resistance and liver and spleen infiltration. According to the technical scheme, the preparation method comprises the following steps: firstly, adsorbing acid-sensitive polyethylene glycol-polyethyleneimine macromolecules on the surfaces of Prussian blue nanoparticles through electrostatic interaction and hydrogen-bond interaction; secondly, the CXCR4 antagonistic polypeptide (E5) and hyaluronic acid are connected with polyethyleneimine molecules on the surfaces of the prussian blue nanoparticles through chemical bonds; thirdly, daunorubicin is adsorbed to the surfaces of the prussian bluenanoparticles through hydrogen bond interaction. The preparation method is simple and mild, materials are safe and easy to obtain, good biocompatibility is achieved, a prepared carrier has the blood long-circulation capacity, the tumor cell double-targeting capacity, the lysosome escape capacity and the acid-sensitive drug release capacity, the mouse leukemia treatment effect can be effectively enhanced, and bone marrow homing and liver and spleen infiltration are inhibited.

Description

technical field [0001] The invention belongs to the field of nanomedicine, and in particular relates to the preparation of a targeted drug delivery system for leukemia treatment. Background technique [0002] Acute myeloid leukemia is a malignant clonal disease, mainly manifested in the abnormal proliferation and differentiation of hematopoietic stem cells, leading to hematopoietic failure. Although traditional chemotherapy is widely used, drugs cannot improve the clinical prognosis of patients very well. Minimal residual lesions and cell drug resistance are important factors for the recurrence, metastasis and low survival rate of leukemia patients. In addition, since hematological tumors do not have obvious EPR (enhanced penetration and retention) effects, improving targeting is very important to reduce systemic toxicity in patients. Therefore, finding new targets, eliminating minimal residual lesions, and overcoming cell drug resistance have become major problems to be so...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K33/26A61K31/704A61K47/02A61K47/60A61K47/61A61K47/62A61K47/69A61P35/02A61P35/04B82Y5/00
CPCA61K47/6929A61K47/62A61K47/61A61K47/60A61K47/02A61K41/0052A61K31/704A61K33/26A61P35/02A61P35/04B82Y5/00A61K2300/00
Inventor 张宇白慧媛马明顾宁
Owner SOUTHEAST UNIV
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