Targeted core-shell structure drug-loaded nanoparticle and preparation method thereof

A drug-loaded nanometer, core-shell structure technology, applied in pharmaceutical formulations, anti-tumor drugs, drug combinations, etc., can solve the problems of cell membrane damage, cytotoxicity, insufficient metabolic properties of inorganic nanocarriers, etc. Effects of enrichment and retention, avoidance of degradation and leakage of chemotherapeutic drugs

Active Publication Date: 2021-02-19
LINYI UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

These nanocarriers still have certain limitations, such as the risk that viral vectors may induce immune responses and gene mutations; although liposomes and polymer micelles can effectively deliver siRNA molecules through electrostatic interactions, the positive charges on the surface usually These cationic delivery vehicles tend to cause severe cytotoxicity problems due to enhanced damage to the cell membrane; inorganic nanocarriers are also limited in clinical application due to long-term toxicity and insufficient drug metabolism properties

Method used

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  • Targeted core-shell structure drug-loaded nanoparticle and preparation method thereof
  • Targeted core-shell structure drug-loaded nanoparticle and preparation method thereof
  • Targeted core-shell structure drug-loaded nanoparticle and preparation method thereof

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preparation example Construction

[0059] The preparation method provided by the invention comprises the following steps:

[0060] (1) Dissolving chemotherapeutic drugs, light-emitting conjugated polymers and polystyrene-maleic anhydride copolymers in an organic solvent, under the action of ultrasound, mixing the resulting mixed solution with water, then distilling off the organic solvent and removing the remaining Filtrating the solution to obtain a luminescent drug-loaded core nanoparticle solution;

[0061] (2) mixing the cell-penetrating peptide, the luminescent drug-loaded core nanoparticle solution and the buffer solution to obtain a cell-penetrating peptide-modified luminescent drug-loaded core nanoparticle solution;

[0062] (3) mixing the gene drug and the luminescent drug-loaded core nanoparticle solution modified by the cell-penetrating peptide to obtain a drug-loaded core nanoparticle solution;

[0063] (4) mixing calcium chloride, nucleic acid aptamer, chemotherapeutic drugs and drug-loaded core n...

Embodiment 1

[0082] Preparation of luminescent drug-loaded core nanoparticles (D / CPNPs) solution:

[0083] Preparation of core luminescent drug-loaded nanoparticles by nano-reprecipitation method, the steps are as follows:

[0084] (1) The chemotherapeutic drug doxorubicin (DOX), luminescent conjugated polymer (CN-PPV) and polystyrene maleic anhydride copolymer (PSMA) were dissolved in tetrahydrofuran to obtain DOX solution, CN-PPV solution and PSMA solution, the final concentration is 1mg / mL, as the original solution;

[0085] (2) Mix the DOX solution, CN-PPV solution and PSMA solution, and dilute with tetrahydrofuran to obtain a mixed solution, the mass concentrations of DOX, CN-PPV and PSMA in the mixed solution are successively 10 μg / mL and 25 μg / mL and 5 μg / mL.

[0086] (3) Under the action of ultrasound, quickly inject the mixed solution into ultrapure water to obtain a nanoparticle mixed system, and continue to sonicate the nanoparticle mixed system for 1 min.

[0087] (4) Heatin...

Embodiment 2

[0090] Preparation of Luminescent Drug-loaded Core Nanoparticles (D / CPNPs) Solution

[0091] The nano-reprecipitation method is used to prepare luminescent drug-loaded core nanoparticles, and the steps are as follows:

[0092] (1) Dissolve the chemotherapeutic drug doxorubicin (DOX), luminescent conjugated polymer (CN-PPV) and polystyrene maleic anhydride copolymer (PSMA) in dimethyl sulfoxide to obtain DOX solution, CN-PPV -PPV solution and PSMA solution, the final concentration is 1mg / mL, as the original solution;

[0093] (2) Dilute with dimethyl sulfoxide after mixing the DOX solution, CN-PPV solution and PSMA solution to obtain a mixed solution, the mass concentration of DOX, CN-PPV and PSMA in the mixed solution is 20 μg / mL successively , 50 μg / mL and 10 μg / mL.

[0094] (3) Under the action of ultrasound, quickly inject the mixed solution into ultrapure water to obtain a nanoparticle mixed system, and continue to sonicate the nanoparticle mixed system for 2 minutes.

...

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Abstract

The invention relates to the technical field of nano biological medicines, and provides a targeted core-shell structure drug-loaded nanoparticle and a preparation method thereof. The targeted core-shell structure drug-loaded nanoparticle provided by the invention comprises a drug-loaded inner core and a drug-loaded shell layer coating the surface of the drug-loaded inner core, wherein the drug-loaded inner core comprises a light-emitting drug-loaded kernel, a cell-penetrating peptide modified on the surface of the light-emitting drug-loaded kernel and a gene drug adsorbed on the surface of thecell-penetrating peptide; and the drug-loading shell layer comprises a calcium phosphate layer, chemotherapeutic drugs doped in the calcium phosphate layer and nucleic acid aptamers modified on the surface of the calcium phosphate layer. The targeted core-shell structure drug-loaded nanoparticle provided by the invention can target tumor tissue, effectively improves the enrichment and retention of nano-drugs in the tumor tissue, can controllably release chemotherapeutic drugs and gene drugs by utilizing responsiveness in a weakly acidic microenvironment of the tumor tissue, and is low in cytotoxicity and high in safety. The preparation method provided by the invention is mild in reaction, simple to operate and good in repeatability.

Description

technical field [0001] The invention relates to the technical field of nano-biomedicine, in particular to a drug-loaded nanoparticle with a targeting core-shell structure and a preparation method thereof. Background technique [0002] Cancer is a serious threat to human health. The current clinical treatment of cancer mainly includes surgical resection and postoperative radiotherapy and chemotherapy. Synergistic treatment strategies provide an effective solution to overcome the shortcomings of monotherapy. At the same time, the emergence of emerging therapies such as phototherapy, gene therapy, and immunotherapy provides more possibilities for synergistic therapy. In order to reduce the toxic and side effects of chemotherapy drugs, realize the targeted delivery and controlled release of chemotherapy drugs, scientists have focused their research on targeted intelligent responsive nano-drug carriers, and have made remarkable progress. Compared with normal tissue, tumor tissue...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/42A61K47/26A61K47/02A61K47/34A61K31/704A61K31/7088A61P35/00
CPCA61K9/5169A61K9/5146A61K9/5123A61K9/5115A61K31/704A61K31/7088A61P35/00A61K2300/00
Inventor 李琼王奕霖熊雪帆杜海蓉张书圣
Owner LINYI UNIVERSITY
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