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Carboxymethyl chitosan nanoparticles modified with glycyrrhizic acid, preparation method and application thereof

A technology of carboxymethyl chitosan and nanoparticles, which is applied in the field of liver tumor-targeted glycyrrhizic acid modified carboxymethyl chitosan nanoparticles and its preparation, can solve the problem of liver cancer cells that have not been shown to have active targeting and have not yet been identified. Effectively exert the active targeting effect of glycyrrhizic acid and other issues to achieve the effect of improving cell uptake efficiency, realizing long circulation in the body, and avoiding clearance

Inactive Publication Date: 2012-02-22
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Glycyrrhizic acid is used as a targeting ligand to modify chitosan nano-carriers. Chinese patent CN101006983A discloses a preparation method of glycyrrhizinate-modified chitosan / carboxylated chitosan composite drug-loaded nanoparticles. It is only suitable for loading water-soluble drugs; it only proves that the nanoparticles can be targeted to hepatic parenchymal cells, but it does not show that it has active targeting to liver cancer cells; and compared with chitosan, glycyrrhizinate The cellular uptake of modified chitosan / carboxylated chitosan composite nanoparticles was only increased by about 2 times, and the active targeting effect of glycyrrhizic acid was not effectively exerted

Method used

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  • Carboxymethyl chitosan nanoparticles modified with glycyrrhizic acid, preparation method and application thereof
  • Carboxymethyl chitosan nanoparticles modified with glycyrrhizic acid, preparation method and application thereof
  • Carboxymethyl chitosan nanoparticles modified with glycyrrhizic acid, preparation method and application thereof

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Embodiment 1

[0053] The preparation of embodiment 1 carboxymethyl chitosan nanoparticles

[0054] Take 1 g of carboxymethyl chitosan with a molecular weight of 10,000 Da, add it to 100 mL of water, and stir at room temperature until completely dissolved. Heat to 40°C, add 0.5 mL methyl methacrylate, stir for 20 min, add 0.05 g ammonium persulfate, slowly raise the temperature to 70°C, and continue the reaction for 24 h. The milky white nanoparticle suspension obtained from the reaction was dialyzed and purified in a 14,000 Da semipermeable membrane, and freeze-dried.

Embodiment 2

[0055] The preparation of embodiment 2 carboxymethyl chitosan nanoparticles

[0056] Take 1 g of carboxymethyl chitosan with a molecular weight of 10,000 Da, add it to 100 mL of water, and stir at room temperature until completely dissolved. Heat to 30°C, add 0.25 mL of methyl methacrylate, stir for 10 min, add 0.01 g of ammonium persulfate, slowly raise the temperature to 75°C, and continue the reaction for 12 h. The milky white nanoparticle suspension obtained from the reaction was dialyzed and purified in a 14,000 Da semipermeable membrane, and freeze-dried.

Embodiment 3

[0057] The preparation of embodiment 3 carboxymethyl chitosan nanoparticles

[0058] Take 1 g of carboxymethyl chitosan with a molecular weight of 10,000 Da, add it to 100 mL of water, and stir at room temperature until completely dissolved. Heat to 50°C, add 4 mL of methyl methacrylate, stir for 30 min, add 0.2 g of ammonium persulfate, slowly raise the temperature to 85°C, and continue the reaction for 2 h. The milky white nanoparticle suspension obtained from the reaction was dialyzed and purified in a 14,000 Da semipermeable membrane, and freeze-dried.

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Abstract

The invention belongs to the technical field of nano materials, and in particular relates to carboxymethyl chitosan nanoparticles modified with glycyrrhizic acid, as well as a preparation method and application thereof. The nanoparticles disclosed by the invention are in a core-shell type; a hydrophobic polymer serves as a kernel packaged medicament; and carboxymethyl chitosan serves as a hydrophilic shell and is covalently linked with hepatic targeting ligand glycyrrhizic acid. The preparation method comprises the following steps of: firstly grating and copolymerizing carboxymethyl chitosan and hydrophobic monomers and self-assembling to form nanoparticles in the action of an initiator; secondly, oxidizing glycyrrhizic acid to obtain a glycyrrhizic acid aldehyde solution, mixing the glycyrrhizic acid aldehyde solution with the nanoparticles at a certain proportion and introducing targeting groups, and carrying out ultrasonic loading on the medicament. Compared with the prior art, the preparation method is simple and easy to control and has good repeatability and better stability and safety; and the targeting property and the tumor-inhabiting effect of the anti-tumor medicament can be strengthened remarkably. The nanoparticles serve as a targeting delivery vector for hydrophobic medicaments or molecular probes and can be used for treatment and diagnosis of liver diseases.

Description

technical field [0001] The invention belongs to the technical field of targeting nanomaterials, and in particular relates to liver tumor targeting glycyrrhizic acid modified carboxymethyl chitosan nanoparticles and a preparation method and application thereof. Background technique [0002] Liver diseases such as liver cancer and hepatitis are common and frequently-occurring diseases that seriously threaten human health. Drugs in conventional dosage forms are distributed throughout the body after intravenous, oral or local injection, causing serious side effects. The targeted drug delivery system can selectively deliver the drug to the diseased part of the liver through the carrier material, reduce the toxic and side effects on normal tissues, reduce the dosage and frequency of administration, and improve the efficacy of the drug. Nanoparticles are solid colloidal particles with a particle size of 10-1000 nm made of natural or synthetic polymer materials. As a new drug delive...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K47/36A61P35/00
Inventor 印春华施丽丽
Owner FUDAN UNIV
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