Cationic liposome and preparation method thereof

A cationic liposome and cationic technology, applied in liposome delivery, pharmaceutical formulations, antibody medical components, etc., can solve problems such as retention, reduced immune efficacy of liposome vaccines, and inability to effectively enter lymphatic organs

Active Publication Date: 2013-03-20
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in fact, due to the influence of physical and chemical factors such as particle size, charge, and surface properties, most of the liposome vaccine stays at the injection site after being injected into the body, and cannot effectively enter the lymphoid organs, which reduces the quality of the liposome vaccine. immune potency

Method used

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  • Cationic liposome and preparation method thereof
  • Cationic liposome and preparation method thereof
  • Cationic liposome and preparation method thereof

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preparation example Construction

[0053] Provide the preparation method of the above-mentioned cationic liposome of one embodiment below, comprise the steps:

[0054] S10, providing polyethylene glycol derivatized phospholipids, linking mannose or mannoside to the polyethylene glycol derivatized phospholipids to obtain polyethylene glycol derivatized phospholipids modified with mannose or mannan oligosaccharides.

[0055] Polyethylene glycol derivatized phospholipids can be purchased directly, obtained by linking one end of polyethylene glycol (PEG) to phospholipids and amination of the other end.

[0056] In this embodiment, one end of polyethylene glycol is connected with distearoylphosphatidylethanolamine (DSPE), which is denoted as DSPE-PEG. In other embodiments, one end of polyethylene glycol can also be selected to be connected to other types of phospholipids, which can be any one of the above-mentioned cationic lipids or neutral phospholipids.

[0057] Mannose or mannan oligosaccharides are linked to t...

Embodiment 1

[0066] D-mannose was linked to DSPE-PEG2000 through aldehyde-amino condensation to obtain D-mannose-modified DSPE-PEG2000. DOTAP, DOPC and D-mannose-modified DSPE-PEG2000 were respectively dissolved in a mixed solvent of chloroform and methanol with a volume ratio of 2:1, and then the D-mannose-modified The ratio of the moles of DSPE-PEG2000 to the total moles of DOTAP and DOPC is 1:50, and the three are mixed to obtain a mixed solution, which is then placed in a round-bottomed flask. Rotate and dry the mixture with a steady nitrogen flow to form a uniform film. After vacuum drying overnight, add PBS buffer containing antigen protein BSA-FITC and place it at 4°C for hydration, and then ultrasonic water bath for 10min The polycarbonate membrane was extruded twice to obtain cationic liposomes coated with BSA-FITC, denoted as LP-PEG-Man.

Embodiment 2

[0068]Fucose was linked to DSPE-PEG2000 through aldehyde-amino condensation to obtain fucose-modified DSPE-PEG2000. DDAB, DOPC and fucose-modified DSPE-PEG2000 were respectively dissolved in a mixed solvent of chloroform and methanol with a volume ratio of 2:1, and then according to the molar ratio of DDAB and DOPC at 7:3, the fucose-modified DSPE-PEG2000 The ratio of the number of moles of PEG2000 to the total number of moles of DDAB and DOPC is 2:25, and the three are mixed to obtain a mixed solution, which is then placed in a round-bottomed flask. Rotate and dry the mixture with a stable helium flow to form a uniform film. After vacuum drying overnight, add PBS buffer containing antigenic protein BSA-FITC the next day and place it at 4°C for hydration, then ultrasonic water bath for 10min The polycarbonate membrane was extruded twice to obtain cationic liposomes coated with BSA-FITC.

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Abstract

The invention discloses a cationic liposome, comprising cationic lipid, neutral phospholipid, polyethylene glycol derivatived phospholipid and mannose or mannan oligosaccharide, wherein a shell-shaped phospholipid bilayer is formed by phospholipid molecules in the the cationic lipid, the neutral phospholipid and the polyethylene glycol derivatived phospholipid; and mannose- or mannan oligosaccharide- modified polyethylene glycol derivatived phospholipid is formed by connecting the mannose or the mannan oligosaccharide with one end of the polyethylene glycol derivatived phospholipid. By adding the mannose- or mannan oligosaccharide- modified polyethylene glycol derivatived phospholipid, targeting property and enrichment in lymph glands of antigen-presenting cells are increased; the cationic liposome has an immunologic enhancement effect; and the immune efficacy of liposome-encapsulated vaccines can be increased. The invention also provides a preparation method of the cationic liposome.

Description

【Technical field】 [0001] The invention relates to the field of immunotherapy, in particular to a cationic liposome and a preparation method thereof. 【Background technique】 [0002] Vaccines are an important means to prevent and control the occurrence and development of infectious diseases. Immune adjuvants (also known as non-specific immune proliferators) are indispensable components in vaccines, which can effectively promote specific immune responses induced by vaccines. With the rapid development of vaccine research, new genetically engineered vaccines are gradually replacing traditional live attenuated vaccines and inactivated vaccines. Compared with traditional vaccines, genetically engineered vaccines have the advantages of high purity, strong specificity, and good safety. However, due to their generally poor immunogenicity, it is urgent to combine effective immune adjuvants to improve the immune efficacy of vaccines. [0003] Liposome nanoparticles are spherical enti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K39/39A61K47/34
Inventor 马轶凡庄燕蔡林涛
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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