A kind of cationic phospholipid-polymer nanoparticle and preparation method thereof

A nanoparticle and cationic liposome technology, which is applied in the field of cationic phospholipid-polymer nanoparticle and its preparation, can solve problems such as difficult loading of macromolecular plasmid DNA, and achieve good biodegradability, high endocytosis efficiency, and stable properties Effect

Active Publication Date: 2018-05-25
ZHUHAI INST OF ADVANCED TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] In order to solve the above problems, the invention provides a cationic phospholipid-polymer nanoparticle, which contains cationic liposomes, which can absorb negatively charged DNA, and solve the problem of phospholipids in the prior art. -The problem that polymer nanoparticles are difficult to load macromolecular plasmid DNA; the present invention also provides a preparation method of cationic phospholipid-polymer nanoparticles, the preparation method is simple in process, easy to operate, and can be prepared on a large scale

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  • A kind of cationic phospholipid-polymer nanoparticle and preparation method thereof

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Embodiment 1

[0038] A preparation method of cationic phospholipid-polymer nanoparticles, comprising the following steps:

[0039] (1) Soybean lecithin and cationic liposome are dissolved in the ethanol aqueous solution that mass concentration is 4% with mass ratio as 1:4, obtain mixed solution, the total volume of mixed solution is 80mL, the concentration of soybean lecithin in mixed solution The concentration of the cationic liposome is 0.05mg / mL, and the cationic liposome is DOTAP; keep the mixed solution at a temperature of 60°C, adjust the pressure to 1400bar, and initially emulsify for 2min to obtain an emulsion;

[0040] (2) Dissolve the polymer PLGA with a molecular weight of 5000 in acetonitrile to obtain a polymer solution with a concentration of 1mg / mL, with a total volume of 20mL; drop the polymer solution into the emulsion, keep the temperature at 60°C, and keep the pressure 1400bar, continue to emulsify for 6min, and form 100mL solution containing cationic phospholipid-polymer...

Embodiment 2

[0044] A preparation method of cationic phospholipid-polymer nanoparticles, comprising the following steps:

[0045] (1) soybean lecithin and cationic liposome are dissolved in the ethanol aqueous solution that mass concentration is 4% with mass ratio as 1:3, obtain mixed solution, the total volume of mixed solution is 80mL, the concentration of soybean lecithin in mixed solution The concentration of the cationic liposome is 0.05 mg / mL, and the cationic liposome is DOTAP; keep the mixed solution at a temperature of 90°C, adjust the pressure to 500 bar, and initially emulsify for 5 minutes to obtain an emulsion;

[0046] (2) Dissolve polymer PLA with a molecular weight of 15000 in acetocyanide to obtain a polymer solution with a concentration of 1mg / mL, with a total volume of 20mL; drop the polymer solution into the emulsion, keep the temperature at 90°C, and keep the pressure 500bar, continue to emulsify for 4min, form 100mL the solution that contains cationic phospholipid-pol...

Embodiment 3

[0048] A preparation method of cationic phospholipid-polymer nanoparticles, comprising the following steps:

[0049] (1) Soybean lecithin and cationic liposome are dissolved in the ethanol aqueous solution that mass concentration is 4% with mass ratio as 1:5, obtain mixed solution, the total volume of mixed solution is 800mL, the concentration of soybean lecithin in mixed solution The concentration of cationic liposome is 0.05mg / mL, cationic liposome is 0.25mg / mL, and cationic liposome is DOTAP; keep the mixed solution at a temperature of 70°C, adjust the pressure to 1000bar, and initially emulsify for 1min to obtain an emulsion;

[0050] (2) Dissolve the polymer PLGA with a molecular weight of 10000 in acetone to obtain a polymer solution with a concentration of 1 mg / mL, with a total volume of 200 mL; add the polymer solution dropwise to the emulsion, keep the temperature at 70 °C and the pressure at 1000 bar , continue to emulsify for 5min to form 1000mL solution containing ...

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Abstract

The invention provides a cationic phospholipid-polymer nanoparticle, comprising an inner core and an outer shell, the inner core is a polymer, the outer shell is a cationic liposome and a phospholipid, and the cationic liposome and the phospholipid are coated on On the polymer surface, the polymer is polyglycolide lactide or polylactic acid. The cationic phospholipid-polymer nanoparticles have uniform particle size and stable properties, and can carry DNA into cells. The present invention also provides a preparation method of cationic phospholipid-polymer nanoparticles, which adopts a one-step high-pressure homogenization method to prepare cationic phospholipid-polymer nanoparticles, which is simple to operate and can prepare large doses of cationic phospholipid-polymer nanoparticles. The scale-up production and clinical research of the nanoparticles provide a basis, and the preparation method is simple and easy to implement and easy to popularize.

Description

technical field [0001] The invention relates to the field of drug carriers, in particular to a cationic phospholipid-polymer nanoparticle and a preparation method thereof. Background technique [0002] In recent years, the two mainstream nanocarriers represented by polymer nanoparticles and nanoliposomes can efficiently encapsulate and transport drugs, and have become a research hotspot for scientists from all over the world. Polymer nanoparticles have strong drug encapsulation ability, high cell endocytosis efficiency, and long circulation time in vivo. Nanoliposomes have the characteristics of excellent biological safety, high transport capacity, and simple preparation process. Phospholipid-polymer nanoparticles prepared by combining the respective advantages of polymers and phospholipids have been widely used in drug delivery. [0003] Gene therapy has brought hope for the effective prevention and treatment of some major diseases that have plagued human beings for a lon...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K47/34A61K47/24A61K48/00
Inventor 蔡林涛郑明彬陈泽罗震宇赵鹏飞龚萍
Owner ZHUHAI INST OF ADVANCED TECH
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