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A kind of hypoxia-improved cisplatin prodrug liposome preparation and its preparation method and application

A liposome preparation and liposome technology, applied in the field of biomedicine, can solve problems such as insufficient oxygen and nutrient supply, limited therapeutic effects of radiotherapy and chemotherapy, and uneven distribution of blood vessels, so as to improve the therapeutic effect of radiotherapy and chemotherapy and enhance the killing effect , the effect of inhibiting tumor growth

Active Publication Date: 2020-02-21
JE & NA BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the therapeutic effect of radiotherapy and chemotherapy is still limited by the complex tumor microenvironment
[0004] Due to the rapid growth of malignant tumors and the uneven distribution of internal blood vessels, it is easy to cause insufficient supply of oxygen and nutrients in the tumor tissue, which in turn leads to severe hypoxia of cancer cells in some areas and even cancer cell metastasis

Method used

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  • A kind of hypoxia-improved cisplatin prodrug liposome preparation and its preparation method and application
  • A kind of hypoxia-improved cisplatin prodrug liposome preparation and its preparation method and application
  • A kind of hypoxia-improved cisplatin prodrug liposome preparation and its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0053] Embodiment 1, the preparation of liposome-cisplatin prodrug-catalase preparation

[0054] Fully oxidize cisplatin and hydrogen peroxide in an aqueous solution to obtain a product dissolved in DMSO and react with succinic anhydride to generate a tetravalent cisplatin prodrug (see document 1. Rational Design of Polyion Complex Nanoparticles to Overcome Cisplatin Resistance in Cancer for specific preparation content) Therapy.Advancematerials,2014,26,931-936. Literature 2.Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum (IV)Warheads.J.Am.Chem.Soc.,2009,131,14652–14653), obtained before cisplatin After the drug was activated by EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) and NHS (N-hydroxysuccinimide), it was dissolved in certain chloroform, ethanol and water react with phosphatidylethanolamine in a molar ratio of 2:1 in a mixed solvent to generate phosphatidylethanolamine-cisplatin prodrug (DSPE-Pt(IV)).

[005...

Embodiment 2

[0057] Embodiment 2, preparation of liposome-cisplatin prodrug-catalase-fluorescent dye preparation

[0058] After weighing DSPE-Pt(IV), DPPC, CH, DSPE-PEG (5k, Laysan bio company) and DiD according to the molar ratio of 8:8:4:1:1, according to the steps in Example 1 Prepared to obtain liposome-cisplatin prodrug-catalase-fluorescent dye preparation.

Embodiment 3

[0059]Embodiment 3, the property detection of liposome-cisplatin prodrug-catalase preparation

[0060] The liposome-cisplatin prodrug-catalase preparation prepared in Example 1 was qualitatively detected, and transmission electron microscope detection and dynamic light scattering were carried out respectively.

[0061] Among them, the results of transmission electron microscope detection are as follows: figure 1 As shown, the results show that the liposome-cisplatin prodrug-catalase preparation prepared in Example 1 is distributed in a monodisperse state in water, indicating that the liposome-cisplatin prodrug-peroxidase preparation prepared by the present invention The catalase preparation has a uniform particle size and is well dispersed in water.

[0062] The results of dynamic light scattering were as follows: figure 2 As shown, the results show that the liposome-cisplatin prodrug-catalase preparation prepared in Example 1 mainly concentrates on about 100nm in water par...

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Abstract

The invention relates to the technical field of biological medicines, and relates to a hypoxia improvement-based radiosensitizing cisplatin prodrug liposome preparation as well as preparation and application thereof, in particular to liposome-cisplatin prodrug-catalase as well as preparation and application thereof, especially application thereof to improvement of hypoxia in a tumor area so as to sensitize radiotherapy in combination with chemotherapy. The liposome preparation provided by the invention mainly comprises a liposome, a cisplatin prodrug and catalase, is uniform in particle size and good in dispersion in water, has the particle size in water mainly concentrating at about 100nm, can simultaneously load photosensitive molecules and the catalase, is an ideal drug carrier, and has good in-vivo pharmacokinetic behaviors. Experiments show that the liposome-cisplatin prodrug-catalase preparation is highly enriched on a tumor site, and can very well improve a hypoxic condition of a tumor environment and increase the oxygen content to sensitize radiotherapy, and through the combination with the chemotherapeutic effect of the cisplatin, a good synergistic tumor-treating effect is ultimately achieved.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a hypoxia-improved cisplatin prodrug liposome preparation and its preparation method and application. Background technique [0002] Tumor refers to the neogrowth formed by the proliferation of local tissue cells in the body under the action of various tumorigenic factors, because this neogrowth is mostly in the form of space-occupying blocky protrusions, also known as neoplasm (neoplasm) . According to the cell characteristics of new organisms and the degree of harm to the body, tumors are divided into two categories: benign tumors and malignant tumors, and cancer is the general term for malignant tumors. Compared with benign tumors, malignant tumors grow faster and show invasive growth, are prone to bleeding, necrosis, ulcers, etc., and often have distant metastasis, resulting in emaciation, weakness, anemia, loss of appetite, fever, and severe organ damage. Impairment of ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K47/54A61K47/69A61K41/00A61K33/243A61K38/44A61P35/00
CPCA61K9/1271A61K33/24A61K38/44A61K41/0038C12Y111/01006A61K2300/00
Inventor 刘庄张蕊冯良珠
Owner JE & NA BIOTECH CO LTD
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