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A delivery system, preparation method and application based on nanoliposome

A nano-liposome and delivery system technology, applied in the field of medicine, can solve the problems of unstable ozone solubility, ineffective mitosis and fragmentation of cells, etc., to improve the tumor immune microenvironment, promote the increase of quantity and activity, and improve hypoxia. The effect of the environment

Active Publication Date: 2022-04-29
WEST CHINA HOSPITAL SICHUAN UNIV
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Problems solved by technology

①The direct killing effect is mainly that the high-energy charged particles directly act on the DNA in the cell, thereby causing DNA single-strand or double-strand breaks; ②The indirect killing effect is mainly through the ionization of water molecules and oxygen inside and outside the tumor cells by high-energy X-rays to generate reactive oxygen species Free radicals (ROS), such as hydroxyl radicals (OH·), singlet oxygen, etc., cause DNA single-strand or double-strand breaks, making cells unable to effectively mitosis
However, ozone is unstable and has low solubility, so there is a need for an efficient and stable ozone delivery system that can deliver ozone to the tumor microenvironment

Method used

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Embodiment Construction

[0035] The present invention will be further described below in conjunction with specific embodiments and accompanying drawings.

[0036] Such as figure 1 As shown, a nanoliposome-based ozone delivery system was prepared using perfluorodecalin, a ten-carbon perfluorocarbon (PFC) compound, as follows:

[0037] Step 1: Add 400 μL perfluorodecalin (PFD) and 100 μL Tween-80 to the solvent, the solvent is 600 μL acetic acid with a concentration of 0.6 mol / L; vortex for 15 minutes, then sonicate at 35W for 10 seconds, pause for 5 seconds , circulated 10 times altogether, can obtain perfluorodecalin emulsion (PFD emulsion, figure 2 A).

[0038] Step 2: 300 mg lecithin and 100 mg cholesterol were dissolved in a solvent, and the solvent was 10 mL of chloroform. Under the condition of a water bath at 42°C, the solution was rotary evaporated under reduced pressure, and then dried in a round-bottomed flask to form a lipid film.

[0039] Step 3: Add 10 mL of the perfluorodecalin emuls...

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Abstract

The invention discloses a preparation method and application based on a nanoliposome delivery system. The nanoliposome is a granular structure composed of an outer shell and an emulsion in the outer shell; the outer shell is composed of lecithin and cholesterol, and the emulsion is composed of whole Composition of fluorocarbons and Tween‑80. In the present invention, perfluorocarbons are firstly prepared into an emulsion, and then the emulsion is encapsulated in liposomes; when combined with ozone, ozone is encapsulated in liposomes, increasing the stability of ozone and the concentration of ozone carried, and stably carrying ozone Delivered into the tumor microenvironment, it is effectively endocytized by tumor cells; compared with oxygen, under high-energy X-ray irradiation, on the one hand, ozone releases and produces a large number and higher concentration of hydroxyl free radicals, which can directly kill tumor cells; On the one hand, the oxygen released by ozonolysis can enhance the killing sensitivity of tumor cells to radiation; finally, the released oxygen can improve the hypoxic state in the tumor microenvironment, providing a friendly environment for tumor-infiltrating lymphocytes.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to a preparation method and application of a nanoliposome-based delivery system. [0002] technical background [0003] Radiation therapy is one of the main options for local treatment of tumors. The principle is that when a large amount of radiation enters the organism, it will destroy the DNA, RNA, protein and other biological functional macromolecules of the cell. In particular, it causes double-strand breaks in important genetic material DNA (deoxyribose nucleic acid), thereby causing irreparable damage to cells in a state of vigorous division (mostly tumor cells). According to different radiation sources, radiation therapy can be divided into ①radiotherapy based on high-energy X-rays; ②radiotherapy based on high-energy charged particles. The lethal effect of radiotherapy is further divided into direct and indirect lethal effects. ①The direct killing effect is mainly that th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K33/00A61K47/06A61P35/00
CPCA61K9/127A61K33/00A61K47/06A61P35/00
Inventor 石虎兵李燕雏郑丹
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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