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Polypeptide drug-loaded temperature-sensitive liposome and preparation method and application thereof

A liposome and drug-loading technology, which is applied in the field of biomedicine, can solve the problems that effective drugs are difficult to exert a rapid killing effect, drug resistance, slow drug release, etc.

Active Publication Date: 2020-06-19
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some liposomes have the defect of slow local drug release, making it difficult for effective drugs to exert their own rapid killing effect, and even produce drug resistance at low drug concentrations with sustained release

Method used

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  • Polypeptide drug-loaded temperature-sensitive liposome and preparation method and application thereof
  • Polypeptide drug-loaded temperature-sensitive liposome and preparation method and application thereof
  • Polypeptide drug-loaded temperature-sensitive liposome and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0125] The preparation of embodiment 1 liposome (Lipo) and its dissolving experiment in PBS solution

[0126] The DSPE-PEG-MAL solution and the amino group contained in the P12 polypeptide are mixed and reacted at room temperature to form DSPE-PEG-P12, which is purified and freeze-dried for later use. DSPE-PEG-2000 was prepared into 5 mg / mL solution in chloroform, DSPE-PEG-P12 (the molecular weight of the PEG segment was 2000) was prepared into 5 mg / mL solution in chloroform, cholesterol was prepared into 10 mg / mL solution in chloroform, DPPC Prepare a 10mg / mL solution with chloroform. Mix the above solutions at a molar ratio of 2:1.5:4:15:5, mix thoroughly, heat in a water bath at 45°C, and spin-evaporate for 1 hour, then place it in a vacuum oven at 60°C overnight, then add 5mL of PBS solution, ultrasonic water bath 60°C for 45 minutes to hydrate it into a PBS solution of polypeptide nanoliposomes. The solution prepared above was placed in a refrigerator at 4°C.

[0127...

Embodiment 2

[0129] The preparation of embodiment 2 polypeptide liposome (P12-Lipo) and its dissolving experiment in PBS solution

[0130]DSPE-PEG-2000 was prepared into 5 mg / mL solution in chloroform, DSPE-PEG-P12 (the molecular weight of the PEG segment was 2000) was prepared into 5 mg / mL solution in chloroform, cholesterol was prepared into 10 mg / mL solution in chloroform, DPPC Prepare a 10mg / mL solution with chloroform. Mix the above solutions according to the mass ratio of 2:1.5:4:15:5, mix thoroughly, heat in a water bath at 45°C, spin evaporate for 1 hour, and then place it in a vacuum oven at 60°C overnight, then add 5mL of PBS solution, ultrasonic water bath 60°C, 45min, to make it hydrated into a PBS solution of polypeptide nano liposomes. The solution prepared above was placed in a refrigerator at 4°C.

[0131] The concentration of the polypeptide nano-empty liposome (P12-Lipo) was fixed at 100 μM, and the polypeptide nano-liposome (P12-Lipo) was ultrasonically mixed in a 45...

Embodiment 3

[0134] Example 3 FITC-labeled P12 polypeptide molecules (FITC-P12) and P12-Lipo fluorescent nanoliposomes dissolved in PBS Solubility test in solution

[0135] The FITC-labeled P12 polypeptide molecule (ie, FITC-P12 polypeptide molecule) was prepared into a 1 mg / mL solution with glucose buffer solution, and the concentration of the FITC-P12 polypeptide was 40 μM. In addition, DSPE-PEG-2000 was prepared into 5 mg / mL solution with chloroform, DSPE-PEG-P12-FITC (the molecular weight of the PEG segment was 2000) was prepared with chloroform into 5 mg / mL solution, cholesterol was prepared with chloroform as 10 mg / mL Solution, DPPC was prepared into 10mg / mL solution with chloroform. Mix the above solutions according to the mass ratio of 2:1.5:4:15:5, mix thoroughly, heat in a water bath at 45°C, spin evaporate for 1 hour, and then place it in a vacuum oven at 60°C overnight, then add 5mL of PBS solution, ultrasonic water bath 60 ℃, 45min, make it hydrated to obtain polypeptide ...

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Abstract

The invention provides a polypeptide drug-loaded temperature-sensitive liposome. The drug-loaded temperature-sensitive liposome is formed by self-assembling a polypeptide, a chemotherapeutic drug, a photosensitizer and a liposome, and the polypeptide can be combined with cancer cells expressing or over-expressing chemokine receptor protein CXCR4 in a targeting manner. The invention also provides apreparation method and application of the temperature-sensitive liposome. The drug-loaded temperature-sensitive liposome combining the polypeptide, the photosensitizer and the chemotherapeutic drug has the capability of improving the solubility of the polypeptide in a salt solution, improves the binding efficiency of the polypeptide and the chemokine receptor CXCR4 target protein, improves the enrichment capacity of chemotherapeutic drug at cancer cells and cancer tissues, and shows the characteristic of stronger inhibition of cancer cell migration. On the other hand, the drug loading capacity and in-vivo bioavailability of the chemotherapeutic drug are improved by utilizing the liposome, and accurate and controllable release of the chemotherapeutic drug is realized by utilizing the photosensitizer.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a polypeptide drug-loaded temperature-sensitive liposome and a preparation method and application thereof. Background technique [0002] Cancer is currently the main cause of global morbidity and death, and about 90% of cancer patients die from cancer metastasis and recurrence. Blocking a certain link of cancer metastasis to curb the spread of cancer is very important for the treatment of cancer. Chemokines and chemokine receptors not only participate in normal physiological activities, but also participate in pathological processes such as cancer occurrence, invasion and metastasis, among which the CXCR4 / SDF-1 (or CXCL12) biological chemotactic axis plays a role in the process of cancer migration and invasion. The development of antagonists of CXCR4 chemokine receptor protein is very critical for controlling cancer metastasis and improving cancer cure rate. Since the poly...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K9/127A61K47/42A61K31/704A61P35/00A61P35/02A61P35/04
CPCA61K41/0057A61K9/1271A61K47/42A61K31/704A61P35/00A61P35/02A61P35/04A61K2300/00
Inventor 王琛张凯悦方小翠游青杨延莲
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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