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10-hcpt-loaded phase-change lipid nanoparticles modified by HA-mediated cpps and preparation method thereof

A technology of 10-HCPT and lipid nanoparticles, which is applied in the direction of medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulations, and can solve the problem of difficult to achieve extravascular tumor tissue imaging and treatment, ultrasound The problem of large microbubble particle size and poor imaging effect can achieve the effect of good oxygen carrying capacity, good dispersion and high biological safety

Inactive Publication Date: 2020-05-05
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] As an ultrasound contrast agent, ultrasonic microbubbles have been widely used in the diagnosis of clinical diseases, especially in the diagnosis and differential diagnosis of liver diseases. In addition, as a tool for carrying anti-tumor drugs or genes, they are also used in the treatment of diseases. Widely used in experimental research, but ultrasonic microbubbles cannot pass through the vascular endothelial space (380-780nm) inside the tumor tissue due to their large particle size, making it difficult to achieve imaging and treatment of extravascular tumor tissue
In order to solve this problem, lipid nanoparticles can penetrate the vascular endothelial space of tumor tissue to reach the tumor tissue with a nano-scale particle size, and can also be used as an anti-tumor drug carrier to transport chemotherapy drugs to the tumor site for anti-cancer treatment. Nanoparticles enhance backscatter visualization in aggregated form, which is less effective than ultrasound microbubbles

Method used

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  • 10-hcpt-loaded phase-change lipid nanoparticles modified by HA-mediated cpps and preparation method thereof
  • 10-hcpt-loaded phase-change lipid nanoparticles modified by HA-mediated cpps and preparation method thereof
  • 10-hcpt-loaded phase-change lipid nanoparticles modified by HA-mediated cpps and preparation method thereof

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Embodiment Construction

[0051] 1. The 10-HCPT phase-change lipid nanoparticles (HA / CPPs-10-HCPT-NPs for short) mediated by HA of the present invention modified by CPPs, its specific preparation method is:

[0052] A. Synthesis of DSPE-CG-TAT-GC

[0053] (1) Synthesis of DSPE-PEG-NHS.

[0054] (a) Weigh an appropriate amount of DSPE-PEG-COOH and dissolve it in DCM (dichloromethane), add NHS and DCC at a molar ratio of 1:3:2.5, and stir and react at 37.5°C for 12 hours.

[0055] (b) After the reaction is completed, filter, and the filtrate is vacuum-dried, washed with anhydrous ether, filtered, reconstituted, purified by reverse chromatography, and dried in vacuum.

[0056] (2) Synthesis of DSPE-CG-TAT-GC

[0057] (a) DSPE-PEG-NHS and CG-TAT-GC were dissolved in DMSO respectively, and triethylamine and 20 mM mercaptoethanol were added to CG-TAT-GC in an equimolar ratio.

[0058] (b) Add CG-TAT-GC to DSPE-PEG-NHS, stir and react for 2 hours, add three times the volume of water to dilute, and adjust t...

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Abstract

The invention discloses HA mediated CPPs modified 10-HCPT carried phase change lipid nanoparticles. The nanoparticles include a phospholipid shell membrane, the phospholipid shell membrane carries anti-tumor drugs 10-HCPT, DC-cholesterol is modified on the phospholipid shell membrane, cysteine cell-penetrating peptides are connected to the two sides, and hyaluronic acid is adsorbed to the outer layer of the phospholipid shell membrane. A preparation method of the HA mediated CPPs modified 10-HCPT carried phase change lipid nanoparticles has the advantages that the nanoparticles can achieve specific active targeting and enter deep liver cancer tissue, liquid-gas phase transformation can be performed under in-vitro LIFU radiation, and real-time development and positioned release of anti-tumor drugs can be achieved at the same time.

Description

technical field [0001] The invention relates to the field of ultrasound imaging, in particular to a preparation method and application of HA-mediated CPPs-loaded phase-change lipid nanoparticles loaded with 10-HCPT. Background technique [0002] Hepatocellular carcinoma (HCC) is a malignant tumor with the fifth highest incidence rate and the third highest mortality rate, which greatly endangers the physical and mental health of patients. At present, the best treatment for HCC is still radical surgical resection, but most HCC patients are diagnosed at an advanced stage or have distant metastasis, so the treatment is difficult and the prognosis is poor. Because primary liver cancer is less sensitive to existing systemic chemotherapy drugs, its chemotherapy effect is not good. Therefore, there is an urgent need to explore new targets, new measures and develop new drugs for the treatment of primary liver cancer. [0003] As an ultrasound contrast agent, ultrasonic microbubbles...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/61A61K31/4745A61K49/22A61P1/16A61P35/00
CPCA61K31/4745A61K49/225
Inventor 任建丽周志益赵红雲朱蕾蕾王志刚冉海涛李攀孙阳郝兰
Owner CHONGQING MEDICAL UNIVERSITY