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Temperature-sensitive cationic liposome capable of adsorbing graphene oxide and preparation of temperature-sensitive cationic liposome

A technology of cationic liposomes and graphene, applied in the field of antitumor drugs, can solve the problems of difficulty of cationic liposomes and poor circulation ability, and achieve the effects of prolonging blood circulation time, weakening adsorption, and evading macrophage phagocytosis

Active Publication Date: 2021-12-03
YANSHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, cationic liposomes are still difficult to apply in vivo
The surface of the complex of cationic liposomes and RNA is positively charged, which is prone to non-specific adsorption with negatively charged serum proteins to form large-sized polymers, which are easily cleared by the phagocytic system, resulting in cationic The complex of liposome and RNA has poor circulation ability in blood

Method used

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  • Temperature-sensitive cationic liposome capable of adsorbing graphene oxide and preparation of temperature-sensitive cationic liposome
  • Temperature-sensitive cationic liposome capable of adsorbing graphene oxide and preparation of temperature-sensitive cationic liposome
  • Temperature-sensitive cationic liposome capable of adsorbing graphene oxide and preparation of temperature-sensitive cationic liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), (2,3-dioleoyl-propyl)-trimethylammonium chloride (DOTAP), 1-stearyl -sn-glycero-3-phosphocholine (S-lysoPC), N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoyl-SN-glycero-3-phosphoethanolamine ( DSPE-mPEG2000) four kinds of phospholipids were dissolved in the organic solvent of 12mL chloroform and methanol according to the molar ratio of 66:30:2:2 (chloroform 9mL, methanol 3mL), the mass ratios of the four kinds of phospholipids were DPPC 29.068mg, DOTAP 12.573 mg, S-lysoPC 0.88 mg and DSPE-mPEG 2000 3.366 mg.

[0061] The mixture of phospholipids and organic solvents was placed in a 25mL eggplant-shaped flask for rotary evaporation. The speed of the film gradient pressure method is 48r / min, the rotary evaporation temperature is 45°C, the rotary evaporation gradient pressure is 0.02, 0.04, 0.06, 0.08, 0.1MPa, and the rotary evaporation time at the gradient pressure is 50min, 35min, 22min, 22min, 18min. Hydr...

Embodiment 2

[0066] Dissolve 10 mg graphene oxide in 10 mL H 2 O, the solution was ultrasonically crushed to the nanometer level, the ultrasonic power was 800W, the ultrasonic wave was 2s, the interval was 2s, and the ultrasonication time was 18h. The graphene oxide used has a thickness of 2-10 nm, a particle diameter of 80-150 nm, and a potential of -40-30 mV.

[0067] Add 2mL of 4mg / mL temperature-sensitive cationic liposome solution into a NaCl solution with a pH of 7.4, an ion concentration of 10nmol, and a volume of 6mL, and stir magnetically for 30min to obtain reaction solution 3. The magnetic stirring speed is 175r / min and the temperature is 25°C .

[0068] 2 mL of 1 mg / mL graphene oxide was dropped dropwise into the reaction solution 3, and after the electrostatic adsorption reaction was carried out at a speed of 175 r / min and a temperature of 25 °C for 48 h, centrifuged at a speed of 14000 r / min for 15 min to obtain Temperature-sensitive cationic liposomes adsorbed on graphene ...

Embodiment 3

[0071] 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), (2,3-dioleoyl-propyl)-trimethylammonium chloride (DOTAP), 1-stearyl -sn-glycero-3-phosphocholine (S-lysoPC), N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoyl-SN-glycero-3-phosphoethanolamine ( DSPE-mPEG2000) four kinds of phospholipids were dissolved in the organic solvent of 12mL chloroform and methanol according to the molar ratio of 66:30:2:2 (chloroform 9mL, methanol 3mL), the mass ratios of the four kinds of phospholipids were DPPC 29.068mg, DOTAP 12.573 mg, S-lysoPC 0.88 mg and DSPE-mPEG 2000 3.366 mg.

[0072] Mix 23mg of hydrophobic tumor chemotherapy drug quercetin with phospholipid organic solution.

[0073] The mixture of phospholipids, quercetin and organic solvent was placed in a 25mL eggplant-shaped flask for rotary evaporation. The speed of the film gradient pressure method is 48r / min, the rotary evaporation temperature is 45°C, the rotary evaporation gradient pressure is 0.02, 0.04, 0.06, 0...

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Abstract

The invention discloses a temperature-sensitive cationic liposome capable of adsorbing graphene oxide and a preparation method of the temperature-sensitive cationic liposome, and belongs to the technical field of antitumor drugs. The temperature-sensitive cationic liposome capable of adsorbing the graphene oxide comprises a temperature-sensitive cationic liposome and the graphene oxide adsorbed with the temperature-sensitive cationic liposome. The cationic liposome wraps nucleic acid molecules with negative charges through electrostatic interaction, effective lysosome escape is achieved through the proton sponge effect due to the characteristic of surface positive charges, and nucleic acid and various types of drugs are effectively delivered. The graphene oxide is adsorbed on the surface of the cationic liposome to turn charges into negative charges, so that non-specific protein adsorption is weakened while nucleic acid is protected, macrophage phagocytosis is avoided, and the blood circulation time is prolonged. The graphene oxide adsorbed temperature-sensitive cationic liposome has important application in nucleic acid drug delivery and antitumor drug preparation.

Description

technical field [0001] The invention belongs to the technical field of antitumor drugs, and in particular relates to a temperature-sensitive cationic liposome adsorbing graphene oxide and its preparation. Background technique [0002] Nucleic acid drugs mainly refer to compounds containing nucleotides or deoxynucleotides with genetic characteristics and pharmacological activity, including shRNA, miRNA, siRNA, and plasmid DNA. Nucleic acid drugs are divided into RNA drugs and DNA drugs. During blood delivery, RNA is easily hydrolyzed by RNA hydrolase (RNAse) in serum, recognized and phagocytized by mononuclear phagocytic system (MPS), and easily degraded by various digestive enzymes in lysosomes after entering cells . Only after passing through the "extracellular barrier" outside the cell and the "endosome escape" inside the cell can RNA reach the target site in the cell and finally function. In order to overcome the above obstacles, RNA needs to be wrapped in a carrier to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/52A61K41/00A61K31/7088A61P35/00
CPCA61K47/6911A61K47/52A61K41/0052A61K31/7088A61K45/06A61P35/00A61K2300/00Y02A50/30
Inventor 李健高艳婷栗坤石明刘志伟
Owner YANSHAN UNIV
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