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ROS response type nano-carrier based on microglial cell phenotype regulation and intracerebral iron removal as well as preparation method and application of ROS response type nano-carrier

A technology of microglia and nano-carriers, applied in the direction of non-active ingredient medical preparations, active ingredient-containing medical preparations, pharmaceutical formulations, etc., can solve catastrophic oxidative damage and metal errors in sensitive cells and subcellular structures Positioning and other issues to achieve the effect of no pollution in the preparation process, guaranteed safety, and good stability

Pending Publication Date: 2022-08-02
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Abnormalities in brain iron homeostasis elevate levels of redox-active metals, leading to metal mislocalization and catastrophic oxidative damage to sensitive cellular and subcellular structures

Method used

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  • ROS response type nano-carrier based on microglial cell phenotype regulation and intracerebral iron removal as well as preparation method and application of ROS response type nano-carrier
  • ROS response type nano-carrier based on microglial cell phenotype regulation and intracerebral iron removal as well as preparation method and application of ROS response type nano-carrier
  • ROS response type nano-carrier based on microglial cell phenotype regulation and intracerebral iron removal as well as preparation method and application of ROS response type nano-carrier

Examples

Experimental program
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Effect test

Embodiment 1

[0034] A ROS-responsive nanocarrier (salmeterol@AFt-CPPs nanoparticles) based on microglia phenotype regulation and iron scavenging in the brain, prepared by encapsulating salmeterol with apoferritin. The release of the internally encapsulated salmeterol is controlled release, specifically ROS-sensitive release or pH-sensitive release. The nanoparticles have spherical morphology and an average particle size of 100 nm. The molar ratio of apo and salmeterol was 1:30.

[0035] The above-mentioned preparation method of ROS-responsive nanocarriers (salmeterol@AFt-CPPs nanoparticles) based on microglia phenotype regulation and iron scavenging in the brain includes the following steps:

[0036] (1) Dissolving apoferritin (AFt) in ultrapure water to obtain a first solution with a concentration of 50 mg / mL;

[0037] (2) 8.7 mg of salmeterol was dissolved in 4.8 mL of methanol and fully diluted and dissolved to obtain the second solution;

[0038] (3) 960 μL of the first solution was...

Embodiment 2

[0050] A ROS-responsive nanocarrier (Velanterol@AFt-CPPs nanoparticles) based on microglia phenotype regulation and iron scavenging in the brain, prepared by encapsulating vilanterol with apoferritin. The release of the internally encapsulated vilanterol is controlled release, specifically ROS-sensitive release or pH-sensitive release. The nanoparticles have spherical morphology, an average particle size of 100 nm, and a molar ratio of apoferritin to vilanterol of 1:30.

[0051] The above-mentioned preparation method of ROS-responsive nanocarriers (Villanterol@AFt-CPPs nanoparticles) based on microglia phenotype regulation and iron scavenging in the brain includes the following steps:

[0052] (1) Dissolving apoferritin in ultrapure water to obtain a first solution with a concentration of 50 mg / mL;

[0053] (2) 10.2 mg of vilanterol was dissolved in 5 mL of methanol and fully diluted and dissolved to obtain a second solution;

[0054] (3) 960 μL of the first solution was add...

Embodiment 3

[0057] A ROS-responsive nanocarrier (Velanterol@Ft-CPPs nanoparticles) based on microglia phenotype regulation and iron scavenging in the brain, prepared by encapsulating vilanterol with ferritin. The release of the internally encapsulated vilanterol is controlled release, specifically ROS-sensitive release or pH-sensitive release. The nanoparticles have spherical morphology with an average particle size of 100 nm. The molar ratio of ferritin to vilanterol was 1:30.

[0058] The above-mentioned preparation method of ROS-responsive nanocarriers (Villanterol@Ft-CPPs nanoparticles) based on microglia phenotype regulation and iron scavenging in the brain includes the following steps:

[0059] (1) Dissolving ferritin in ultrapure water to obtain a first solution with a concentration of 50 mg / mL;

[0060] (2) 10.2 mg of vilanterol was dissolved in 5 mL of methanol and fully diluted and dissolved to obtain a second solution;

[0061] (3) 960 μL of the first solution was added to t...

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Abstract

The invention discloses an ROS (reactive oxygen species) response type nano-carrier based on microglia phenotype regulation and intracerebral iron removal as well as a preparation method and application thereof, and belongs to the technical field of medicines, under the dual effects of Alzheimer's disease (AD) pathology intracerebral ROS and a slightly acidic environment, the micro aperture between chain proteins on the surface of the nano-particle carrier is enlarged, and a medicine entrapped in the carrier is released, so that the drug release effect is improved. The hollow carrier acts on microglial cells in the brain, the effect of adjusting the pro-inflammatory M1 phenotype of the microglial cells to the anti-inflammatory M2 phenotype is achieved, due to the affinity of the hollow carrier with iron, excessive iron accumulated in the brain can be adsorbed after the hollow carrier releases the medicine, and the reaction which enables inflammation in the brain to be aggravated and forms high-reactivity and destructive active oxygen and the like under catalysis in the presence of excessive active iron is reduced; and aggregation and oligomerization of A beta protein caused by iron are reduced. Aiming at the pathophysiological characteristics of AD, the invention constructs a multifunctional nano delivery carrier for targeting microglial cell phenotypic regulation and accumulated iron removal for AD treatment.

Description

technical field [0001] The invention belongs to the technical field of medicine, and particularly relates to the preparation of a nanoparticle for treating Alzheimer's disease based on the regulation of microglia phenotype and the clearance of iron in the brain and its application as a drug for treating Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD) is a neurodegenerative disease that occurs in the elderly and is characterized by abnormal brain deposition and cognitive dysfunction. AD not only reduces the quality of life of patients, but also has a high fatality rate. At present, Alzheimer's disease is still incurable. The existing available drugs can appropriately improve the symptoms of patients and may prolong the survival period. Therefore, it is urgent to find effective treatment methods for AD. [0003] The study found that abnormal endogenous stimuli, including reactive oxides (ROS), inflammatory factors, and aggregated Aβ protein, that o...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/54A61K31/137A61K31/167A61K31/27A61K47/42A61P25/28
CPCA61K47/545A61K47/6929A61K47/42A61K31/137A61K31/167A61K31/27A61P25/28
Inventor 赵秀丽赵晓微张九龙
Owner SHENYANG PHARMA UNIVERSITY
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