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Nano-drug for inhibiting injured vascular intimal hyperplasia and application of nano-drug

A biomimetic nanometer and nanoparticle technology, applied in the field of biomedicine, can solve the problems of poor targeting and immune evasion ROS response, and achieve the effects of strong targeting, solubilization and uniform particle size.

Pending Publication Date: 2022-02-18
CHONGQING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

RAPA shows excellent anti-proliferation and immunosuppressive effects, and can be used to inhibit inflammatory response and intimal hyperplasia, but its targeting, immune escape, ROS responsiveness and other functions are poor

Method used

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  • Nano-drug for inhibiting injured vascular intimal hyperplasia and application of nano-drug
  • Nano-drug for inhibiting injured vascular intimal hyperplasia and application of nano-drug
  • Nano-drug for inhibiting injured vascular intimal hyperplasia and application of nano-drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045]Example 1 Synthesis route and principle of carrier PBAP-CDI-Mannose (PCM)

[0046]

[0047] The -OH on PBAP can react with the imidazole structure on CDI to form a lipid bond, by controlling the feed ratio during the synthesis. The combination number of imidazole structure on CDI and PBAP can be controlled. The PBAP-CDI synthesized in this experiment retained an imidazole structure for the next step of combining with mannose. Mannose is a six-carbon sugar with good hydrophilicity. Similarly, the -OH on it can react with the imidazole structure to form a lipid bond. In the experiment, stir overnight at 40°C and add the catalyst 4-dimethylaminopyridine (4-dimethylaminopyridine, DMAP) to ensure the full combination of PBAP-CDI and mannose. Since the PBAP part exhibits hydrophobic properties and the mannose part exhibits hydrophilic properties, the carrier PCM has amphiphilicity, and nanocarriers can be prepared by nanoprecipitation.

[0048] Here are the specific step...

Embodiment 2

[0052] Example 2 Preparation method of biomimetic nanoparticles MM@PMR

[0053] The preparation method of biomimetic nanoparticles MM@PMR, the preparation process is as follows,

[0054] (1) Utilize the PCM and RAPA dissolution dialysis that obtains in the embodiment 1 to obtain described PMR nanoparticle;

[0055] (2) extract macrophage cell membrane;

[0056] (3) Coating the PMR nanoparticles with the macrophage membrane to prepare biomimetic nanoparticles MM@PMR.

[0057] Specifically, the mass ratio of PCM to RAPA is 10:1.

[0058] Specifically, in step (3), a liposome extruder with a pore size of 200 nm is used to blend and extrude the macrophage membrane and the PMR nanoparticles to prepare raw nanoparticles MM@PMR.

[0059] The specific implementation process is listed here:

[0060] (1) Synthesis of PMR loaded with RAPA nanoparticles

[0061] 10 mg of the carrier PCM prepared in Example 1 and 1 mg of RAPA were fully dissolved in 200 μL of DMF, and the above organi...

Embodiment 3

[0071] Example 3 Characterization analysis of bionic particles

[0072] 1. Characterization analysis of particle size, potential and TEM morphology of the prepared PMR and MM@PMR

[0073] The hydration size and potential of the prepared PMR, MM@PMR nanoparticles and macrophage membrane microcapsules (MM) were measured at room temperature by a Malvern laser particle size analyzer, and the results were as follows figure 2 As shown, wherein, the particle diameter of PMR is 109.4nm, and PDI is 0.123, shows that the experiment successfully synthesized the PMR nanoparticle with hydrated particle diameter of about 100nm and the size uniformity of nanoparticle is good, and the size of nanoparticle is concentrated normal distributed. MM@PMR is prepared by co-extruding PMR nanoparticles and macrophage membrane microcapsules. When passing through a nanopore with a certain pore size, physical extrusion will make the flexible lipid microcapsules coat the PMR nanocapsules. On the particl...

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Abstract

The invention relates to the field of biological medicine, and particularly discloses a nano-drug for inhibiting injured endometrial hyperplasia and application thereof. According to the invention, an anti-proliferation drug RAPA is used as a model drug, phenylboronic acid and mannose are used for synthesizing an amphiphilic carrier PBAP-CDI-Mannose (PCM) with ROS responsiveness, the amphiphilic carrier is used for entrapping the RAPA to form a nanoparticle PMR, and a macrophage cell membrane is coated on the nanoparticle PMR to prepare the multifunctional bionic nanoparticle MM-PMR. The bionic nano particle MM (at) PMR prepared by the invention is uniform in particle size, good in dispersity and relatively good in biocompatibility, has an immune escape function, can be used for targeted pathological site drug delivery, and can be used for inhibiting injured vascular intimal hyperplasia when being applied to preparation of drugs for treating vascular injury.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a nanomedicine for inhibiting intimal hyperplasia after damaged blood vessels and an application thereof. Background technique [0002] Cardiovascular disease has become a common disease today, and the research on overcoming related diseases continues. The pathological process of many vascular diseases is related to the abnormal function of intima and media. Intimal hyperplasia caused by vascular injury is considered to be an important factor in many vascular diseases. pathological process. Atherosclerosis (AS) is the main potential cause of stroke, myocardial infarction and cardiac death. The dysfunction caused by endothelial injury is considered to be the initiation of AS, and the injury to the intima after percutaneous interventional therapy is considered to be the cause of surgery. Initiating factors of restenosis. Inflammatory infiltration caused by endothelial damage or dysfunc...

Claims

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Application Information

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IPC IPC(8): C07H23/00C07H1/00A61K9/51A61K31/436A61K47/46A61K47/26A61P35/00A61P37/06
CPCC07H23/00C07H1/00A61K9/5176A61K9/5123A61K31/436A61P35/00A61P37/06
Inventor 吴伟刘博妍钟元焉梦吴帅朱力
Owner CHONGQING UNIV
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