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RGD (Arginine-Glycine-Aspartic Acid) peptide modified double-layer medicine carrying nanometer particle and preparation method thereof

A nanoparticle, RGD sequence technology, applied in the field of biomedicine and nanomedicine, can solve the problems of inability to clinical treatment, difficult to solve the problem of non-selective distribution of drugs in the brain, limited drug amount, etc., to achieve high anti-tumor efficiency and prolong drug effect. Time, effect of reversing drug resistance

Inactive Publication Date: 2013-06-26
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, most of the brain-targeted nanoparticles aimed at overcoming the BBB are still in the stage of in vitro and animal experiments and cannot be used for clinical treatment.
The main reason is that although nanoparticles can increase the concentration of drugs in the brain to a certain extent, the amount of drugs entering the brain is still limited, and it is difficult to solve the problem of non-selective distribution of drugs in the brain throughout the brain tissue. The problem of tumor drug resistance

Method used

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  • RGD (Arginine-Glycine-Aspartic Acid) peptide modified double-layer medicine carrying nanometer particle and preparation method thereof
  • RGD (Arginine-Glycine-Aspartic Acid) peptide modified double-layer medicine carrying nanometer particle and preparation method thereof
  • RGD (Arginine-Glycine-Aspartic Acid) peptide modified double-layer medicine carrying nanometer particle and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0038] 1. Synthesis of RGD-CS

[0039] Weigh 1 μmol of chitosan (CS) with a molecular weight of 1 μmol, dissolve it in 5 ml of acetic acid, and call it solution A; weigh 16 μmol of RGD (CRGDKGPDC), dissolve it in 2.1 ml of sodium acetate buffer, and call it solution B. Weigh 16 μmol NHS-PEG-MAL and add it to solution A in solid form at room temperature. After vortexing for 30 s, add all the reaction solution to solution B, and continue to react at room temperature for 12 h. Then transfer to an ultrafiltration tube with a molecular weight cut-off of 50kDa, perform ultrafiltration at 4000rpm, 30min 5-6 times, remove unreacted PEG-RGD and RGD, collect the upper liquid and freeze-dry to obtain a white loose solid.

[0040] Or: Weigh 1 μmol chitosan (CS) with a molecular weight of 1 μmol, dissolve it in 5ml acetic acid, and call it solution A; weigh 16 μmol RGD (CRGDKGPDC), dissolve it in 2.1ml sodium acetate buffer, and call it solution B. Weigh 16 μmol of Sulfo-SMCC and add it t...

Embodiment 2

[0044] With the preparation method of Example 1, the CRGDKGPDC in the prescription was changed to CRGDKGPEC with the same molar number, and the dosage of other components in the prescription was fixed to prepare CRGDKGPEC-modified nanoparticles.

Embodiment 3

[0046] With the preparation method of Example 1, the CRGDKGPDC in the prescription was changed to CRGDRGPEC with the same molar number, and the dosage of other components in the prescription was fixed to prepare CRGDRGPEC-modified nanoparticles.

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Abstract

The invention belongs to the technical field of biological medicines and nanomedicine and relates to an RGD (Arginine-Glycine-Aspartic Acid) peptide modified double-layer medicine carrying cation nanometer particle. The inner core of the nanometer particle disclosed by the invention is a polylactic acid-hydroxyacetic acid PLGA medicine carrying layer; the outer layer of the nanometer particle is an RGD modified cation polymer layer which is carried with a medicine sensitizer. The nanometer particle can penetrate through blood brain barrier through receptor mediation and electrostatic adsorption action, can be gathered at the brain tumor tissue after entering the brain, can deeply penetrate through the solid parts of the tumor under the RGD mediation to specially combine with tumor new vessel endothelial cells and tumor cells and can enter the cells through endocytosis. The sensitizer dispersed at the outer layer is firstly released to play a role of reversing tumor drug resistance and the medicine dispersed at the inner layer is slowly released, so that the efficient, lasting and safe anti-tumor curative effect of the effect is brought into play.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and nanomedicine, and relates to a polypeptide-modified double-layer drug-loaded cationic nanoparticle and a preparation method thereof. technical background [0002] Studies have reported that malignant glioma is the most common type of primary brain tumor with the highest incidence rate and the most difficult treatment. It has the characteristics of high recurrence rate and high mortality rate, and has long been a difficult point in clinical treatment. At present, the treatment principles for this disease recognized at home and abroad are comprehensive treatment based on surgical resection combined with auxiliary means such as radiotherapy and chemotherapy. Among them, the success or failure of postoperative chemotherapy has a great impact on the quality of life and prognosis of patients. Currently, the chemotherapy drugs widely used in clinical practice mainly include anti-tumor alkylating ...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K47/34A61K47/42A61P35/00
Inventor 姜嫣嫣钱丽丽王峰王科
Owner FUDAN UNIV
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