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HIFU (high intensity focused ultrasound) controlled-release targeted nanometer drug delivery system of brain glioma, and preparation method and application of targeted nanometer drug delivery system

A nano-drug delivery system and glioma technology, applied in the field of glioma-targeted nano-drug delivery system and its preparation, can solve the problems of narrow range of disease types, undeveloped, large particle size, etc. Toxic side effects, increasing accumulation, reducing the effects of toxic side effects

Inactive Publication Date: 2017-08-18
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current drug delivery system regulated by ordinary high-frequency ultrasound is still relatively limited, most of which are liposomes or micelles, and the particle size is relatively large, and the scope of applicable diseases is relatively narrow.
At present, the treatment of high-intensity focused ultrasound HIFU mainly focuses on the visual tissue ablation of subcutaneous tumors such as breast cancer and prostate cancer, and other application fields of HIFU have not yet been developed.

Method used

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  • HIFU (high intensity focused ultrasound) controlled-release targeted nanometer drug delivery system of brain glioma, and preparation method and application of targeted nanometer drug delivery system
  • HIFU (high intensity focused ultrasound) controlled-release targeted nanometer drug delivery system of brain glioma, and preparation method and application of targeted nanometer drug delivery system
  • HIFU (high intensity focused ultrasound) controlled-release targeted nanometer drug delivery system of brain glioma, and preparation method and application of targeted nanometer drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Preparation of nanoparticles NP:

[0055] 1) Nanoparticles NP were prepared by an improved nanoprecipitation method, and accurately weighed polylactic acid-glycolic acid copolymer PLGA-COOH (molecular weight: 50,000, 16mg) modified with carboxyl groups at the end, distearoylphosphatidylethanolamine-polyethylene glycol DSPE -PEG (molecular weight 2000, 3.6mg, 1.8μmol), distearoylphosphatidylethanolamine-polyethylene glycol-maleimide DSPE-PEG-MAL (molecular weight 2000, 0.4mg, 0.1μmol), dissolved in 1mL acetone and mix well. The acetone solution in which the polymer was dissolved was quickly injected into 2 mL of Tris-HCl (10 mM, pH 8.0) solution, and the acetone was removed by vacuum rotary evaporation at 40 ° C to obtain a Tris-HCl dispersed nanoparticle NP solution.

[0056] 2) Add the solution obtained in step 1) into a 4mL ultrafiltration tube (molecular weight cut-off 30000), centrifuge at 2000g for 10min, add deionized water to resuspend to 4mL, repeat this step 3...

Embodiment 2

[0058] Preparation of Angiopep-2 modified nanoparticles ANP:

[0059] 1) Add 100 μL of Angiopep-2 short peptide aqueous solution (1 mg / L) dropwise to the nanoparticle NP solution obtained in Example 1, and stir magnetically at 25° C. and 350 rpm for 2 hours to obtain Angiopep-2 short peptide-modified nanoparticles ANP solution.

[0060] 2) Add the nanoparticle ANP solution obtained in step 2) into a 4mL ultrafiltration tube (molecular weight cut-off 30000), centrifuge at 2000g for 10min, add deionized water to resuspend to 4mL, repeat this step 3 times to remove unbound Angiopep-2 short peptide.

Embodiment 3

[0062] Angiopep-2 modified nanoparticles loaded with doxorubicin Dox, doxorubicin / perfluorooctane (Dox / PFOB), fluorescein DiR, fluorescein DiD ANP-D, ANP-D / P, ANP-DiR, ANP - Preparation of DiD:

[0063] 1) Accurately weigh the polylactic acid-glycolic acid copolymer PLGA-COOH (molecular weight 50000, 16 mg) modified by the terminal carboxyl group, distearoylphosphatidylethanolamine-polyethylene glycol DSPE-PEG (molecular weight 2000, 3.6 mg, 1.8 μmol ), distearoylphosphatidylethanolamine-polyethylene glycol-maleimide DSPE-PEG-MAL (molecular weight 2000, 0.4mg, 0.1μmol), dissolved in 1mL of acetone and mixed well, then added 60μL Adriamycin Dox methanol solution (6.66mg / mL), or a mixed solution of 60 μL adriamycin Dox methanol solution (6.66 mg / mL) and 10 μL perfluorooctane PFOB (19.23 mg / mL), or 2 μL fluorescein DiR solution (1mg / mL), or 2μL fluorescein DiD solution (1mg / mL). Then quickly inject the mixed solution of high molecular polymer, drug, foaming agent and fluorescei...

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Abstract

The invention discloses an HIFU (high intensity focused ultrasound) controlled-release targeted nanometer drug delivery system of brain glioma, and a preparation method and application of the targeted nanometer drug delivery system. The drug delivery system comprises targeting molecules, a drug, a foaming agent and a nano-carrier, wherein the targeting molecules are Angiopep-2 short-peptide, the drug is adriamycin, the foaming agent is perfluorooctane, and the nano-carrier is a high molecular material which is modified by terminal carboxyl and has polylactic acid-glycolic acid copolymer as a main ingredient; the drug and the foaming agent are wrapped and loaded in the nano-carrier together in a wrapping manner; and the targeting molecules are connected to nano-particle surfaces through a covalent linkage manner. The drug delivery system disclosed by the invention can target and highly express the blood brain barrier of an LRP (low-densitylipoprotein receptor-related protein) receptor and brain glioma cells; the accumulation of the drug at a brain glioma position is effectively improved; after the drug is fully accumulated, HIFU irradiation is given to induce the drug to be instantly and fully released at the brain glioma position; the drug concentration in the brain glioma cells is greatly improved; therefore, the treatment effect of the brain glioma is obviously improved; and meanwhile, the toxic and side effect of the drug on normal tissue is effectively reduced.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a brain-targeted drug delivery system, in particular to a brain glioma-targeted nano drug delivery system modified by short peptide Angiopep-2 and controlled by high-intensity focused ultrasound (HIFU) And its preparation method and use. Background technique [0002] Glioblastoma multiforme (GBM) is the most common intracranial primary malignant tumor with the highest mortality rate, and its average survival period is only 14 months. Traditional surgical resection is difficult to completely remove tumor tissue and easily leads to recurrence. The effect of chemotherapy is limited by the blood-brain barrier (BBB). Only 10-20% of chemotherapy drugs such as temozolomide and carmustine can pass through the blood-brain barrier, resulting in a very low rate of drugs entering the brain. In addition, most of the current clinical chemotherapy drugs lack targeting, and the amount ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/704A61K47/34A61K47/42A61P35/00A61N7/00A61N7/02A61M37/00
CPCA61K31/704A61K47/34A61K47/42A61M37/0092A61M2210/0693A61N7/00A61N7/022
Inventor 俞磊罗子淼庞志清金恺庞强闫志强王镜朱建中王依婷
Owner EAST CHINA NORMAL UNIV
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