Multi-functional liposome having oxidation-reduction responsiveness and capable of reinforcing tissue permeation

A liposome and responsive technology, which is applied in the field of multifunctional liposome and its preparation, can solve problems such as difficult to achieve therapeutic effect, and achieve the effect of enhancing synergistic anti-tumor effect, increasing oxygen concentration, and enhancing tissue penetration

Inactive Publication Date: 2019-08-30
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] It is usually difficult to achieve a satisfactory therapeutic effect with a single mode of tumor therapy, and mult...

Method used

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  • Multi-functional liposome having oxidation-reduction responsiveness and capable of reinforcing tissue permeation
  • Multi-functional liposome having oxidation-reduction responsiveness and capable of reinforcing tissue permeation
  • Multi-functional liposome having oxidation-reduction responsiveness and capable of reinforcing tissue permeation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1: the synthetic method of cisplatin prodrug DSPE-S-S-Pt and DSPE-Pt

[0024] (1) Oxidized cisplatin (Pt(IV)-OH): 200 mg cisplatin was fully dissolved in 7.0 mL of 30% H 2 o 2 , stirred at 50°C in the dark for 5 h; cooled to room temperature, centrifuged to collect the precipitate, washed with ice water, ice ethanol, and ice ether successively, and dried in vacuo;

[0025] (2) Carboxylated cisplatin (Pt(IV)-SA): 100 mg Pt(IV)-OH was completely dissolved in 8.3 mL DMSO, added 0.03 g succinic anhydride, reacted at 45°C under nitrogen protection and protected from light for 24 h, cooled to room temperature, centrifuged to remove the precipitate, collected the supernatant solution and lyophilized, the product was successively washed with acetone and glacial ether and dried in vacuum;

[0026] (3) Thiolated cisplatin (Pt(IV)-SA-SH): 210 mg Pt(IV)-SA was completely dissolved in 20 mL chloroform / methanol mixed solution (chloroform:methanol=65:35), and 0.523 mL DIP...

Embodiment 2

[0029] Example 2: Preparation method of a multifunctional liposome with redox responsiveness and enhanced tissue penetration

[0030] (1) Precisely weigh HSPC 19.6 mg, Chol 2.3 mg, DSPE-PEG 2000 8.3 mg, cisplatin prodrug (DSPE-S-S-Pt) 7.3 mg and hydrophobic photosensitizer Ce6 3.6 mg, dissolved in 30 mL chloroform / methanol (V:V=1:1) mixed solution;

[0031] (2) Remove the chloroform / methanol mixed solution by rotary evaporation at 30°C and 70 rpm to obtain a layer of uniform film material;

[0032] (3) After being eluted with 3.52 mL of calcium acetate aqueous solution (150 mM), losartan was added at a mass ratio of phospholipid to losartan (Los) of 10:1, stirred at room temperature for 6 h, and then the cell disruptor was used at 300 Ultrasound for 10 min;

[0033] (4) After the liposome solution was dialyzed with 10wt.% sucrose solution containing 5 mM NaCl and ultrapure water, the multifunctional liposome (Ce6-Lip- S-S-Pt / Los). At the same time, DSPE-S-S-Pt was replaced...

Embodiment 3

[0034] Example 3: Preparation method of a multifunctional liposome with redox responsiveness and enhanced tissue penetration

[0035] (1) Precisely weigh HSPC 21.6 mg, Chol 2.3 mg, DSPE-PEG 2000 8.3 mg, cisplatin prodrug (DSPE-S-S-Pt) 7.9 mg and hydrophobic photosensitizer Ce6 3.6 mg, dissolved in 30 mL of chloroform / methanol (V:V=1:1) mixed solution;

[0036] (2) Remove the chloroform / methanol mixed solution by rotary evaporation at 30°C and 70 rpm to obtain a layer of uniform film material;

[0037](3) After elution with 3.79 mL of calcium acetate aqueous solution (150 mM), losartan was added at a mass ratio of phospholipids to Loss of 8:1, stirred at room temperature for 6 h, and then ultrasonicated at 350 W for 5 min with a cell disruptor;

[0038] (4) After the liposome solution was dialyzed with 10wt.% sucrose solution containing 5 mM NaCl and ultrapure water, the multifunctional liposome (Ce6-Lip- S-S-Pt / Los). At the same time, DSPE-S-S-Pt was replaced by cisplatin ...

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Abstract

The invention discloses a multi-functional liposome having oxidation-reduction responsiveness and capable of reinforcing tissue permeation, and a preparation method and application of the multi-functional liposome. A disulfide bond mediated oxidation-reduction responsiveness DSPE-S-S-chemotherapeutic drug prodrug is modified on the surface of the liposome, a hydrophobic photosensitizer is loaded on a phospholipid bimolecular layer, and a hydrophilic drug capable of reinforcing tissue permeability is entrapped in a water phase in the liposome. The liposome prepared by the preparation method disclosed by the invention can release chemotherapeutic drugs in a manner of oxidation-reduction responsiveness, permeation of the liposome in tumor tissue and infiltration of the liposome in peripheraloxygen are reinforced, the liposome can be used as a pharmaceutical preparation capable of resisting breast cancer, resisting liver cancer, resisting lung cancer or resisting cervical cancer for treating tumors, and the effect of synergistically resisting the tumor with chemotherapy/photodynamic therapy is increased.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a multifunctional liposome which has redox responsiveness and can enhance tissue penetration, a preparation method and application thereof. Background technique [0002] It is usually difficult to achieve a satisfactory therapeutic effect with a single mode of tumor therapy, and multimodal combination therapy can use different mechanisms of action to achieve synergistic anti-tumor effects and improve efficacy. Photodynamic therapy (PDT) is an emerging non-invasive tumor treatment method. Its principle is to use photosensitizers to convert surrounding oxygen molecules into cytotoxic singlet oxygen ( 1 o 2 ), so as to achieve the purpose of killing tumor cells. Chemotherapy is one of the main methods for the treatment of malignant tumors. Combining PDT with chemotherapy can significantly enhance the antitumor effect. At the same time, drugs that enhance ...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K41/00A61K33/243A61K31/4178A61K47/54A61P35/00
CPCA61K9/1277A61K31/4178A61K33/243A61K41/0071A61K47/544A61P35/00A61K2300/00
Inventor 陈名懋田佳李如月张其清陈立
Owner FUZHOU UNIV
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