Hypoxia improvement-based cisplatin prodrug liposome preparation as well as preparation method and application thereof

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

Active Publication Date: 2017-06-06
JE & NA BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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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  • Hypoxia improvement-based cisplatin prodrug liposome preparation as well as preparation method and application thereof
  • Hypoxia improvement-based cisplatin prodrug liposome preparation as well as preparation method and application thereof
  • Hypoxia improvement-based cisplatin prodrug liposome preparation as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1. Preparation of liposome-cisplatin prodrug-catalase preparation

[0054] The cisplatin and hydrogen peroxide are fully oxidized in aqueous solution, and the product is dissolved in DMSO and reacted with succinic anhydride to generate a tetravalent cisplatin prodrug (for specific preparation content, please refer to Literature 1. Rational Design of Polyion Complex Nanoparticles to Overcome Cisplatin Resistance in Cancer Therapy.Advancematerials,2014,26,931-936. Literature 2.Polyvalent Oligonucleotide Gold NanoparticleConjugates as Delivery Vehicles for Platinum(IV)Warheads.J.Am.Chem.Soc.,2009,131,14652–14653), the obtained cisplatin before After the medicine has been activated by EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) and NHS (N-hydroxysuccinimide), it is heated in a certain amount of chloroform, ethanol and water. The phosphatidylethanolamine reacts with phosphatidylethanolamine in a molar ratio of 2:1 to generate phosphatidylethanolami...

Embodiment 2

[0057] Example 2. Preparation of liposome-cisplatin prodrug-catalase-fluorescent dye preparation

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

Embodiment 3

[0059] Example 3. Detection of properties of liposome-cisplatin prodrug-catalase preparation

[0060] The liposome-cisplatin prodrug-catalase preparation prepared in Example 1 was qualitatively tested, and the transmission electron microscopy and dynamic light scattering were performed respectively.

[0061] Among them, the results of transmission electron microscopy 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-preparation prepared by the present invention Catalase preparations have uniform particle size and are well dispersed in water.

[0062] The results of dynamic light scattering detection are as follows figure 2 As shown, the results show that the particle size of the liposome-cisplatin prodrug-catalase preparation prepared in Example 1 is mainly about 100 nm in water.

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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 cisplatin prodrug liposome preparation with improved hypoxia and its preparation method and application. Background technique [0002] Tumor refers to a neogrowth formed by the proliferation of local tissue cells under the action of various tumor-causing factors. This neogrowth is mostly a mass-occupying protrusion, also called 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 grow infiltrating. They are prone to bleeding, necrosis, ulcers, etc., and often have distant metastases, causing weight loss, weakness, anemia, loss of appetite, fever, and severe organs. Impairment of function, etc., eventually causing death of the patient. Due ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/54A61K47/69A61K41/00A61K33/24A61K38/44A61P35/00
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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