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Loaded double-drug nanoparticles and its preparation method and application

A nanoparticle and nanomicelle technology, applied in the field of loaded double-drug nanoparticles and its preparation, can solve problems such as insufficient drug stimulus response, achieve good photodynamic therapy effect, and the effect of simple and easy preparation method

Active Publication Date: 2021-08-17
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, due to the heterogeneity of tumors, the ROS-mediated response to drug stimulation is still insufficient.

Method used

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  • Loaded double-drug nanoparticles and its preparation method and application
  • Loaded double-drug nanoparticles and its preparation method and application
  • Loaded double-drug nanoparticles and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] This embodiment provides a nanoparticle loaded with double drugs and its preparation method.

[0060] 1) Dissolve 10 mg of amphiphilic polymer and 1 mg IR780 in 1 mL of dichloromethane to obtain the first solution; the second solution is 200 μL of 10 mg / ml Doxy aqueous solution; add 200 μL of the second solution to the first solution, and Ultrasonic emulsification in an ice bath with a power of 70 W for 3 minutes to obtain the first emulsion.

[0061] 2) Polyvinyl alcohol is formulated into a 1% aqueous solution, F68 is formulated into a 1% aqueous solution, and the two are mixed to obtain a third solution (polyvinyl alcohol solution: F68 solution = 7:3, volume ratio); add the first emulsion to 4ml In the third solution, ultrasonic emulsification was used with a power of 200W and a time of 5 minutes to obtain the second emulsion.

[0062] 3) At room temperature, the organic solvent was removed by rotary evaporation to obtain the product after rotary evaporation. The s...

Embodiment 2

[0067] This embodiment provides a nanoparticle loaded with double drugs and its preparation method.

[0068] 1) Dissolve 20mg of amphiphilic polymer and 1.1mg IR780 in 1mL of dichloromethane to obtain the first solution; the second solution is 220μL of 10mg / ml Doxy aqueous solution; add 200μL of the second solution to the first solution , ultrasonic emulsification in an ice bath with a power of 70W and a time of 3 minutes to obtain the first emulsion.

[0069] 2) Polyvinyl alcohol is formulated into a 1% aqueous solution, and F68 is formulated into a 1% aqueous solution to obtain a third solution (polyvinyl alcohol: F68=7:3); the first emulsion is added to 4ml of the third solution, and ultrasonic For emulsification, the power is 200W, and the time is 5 minutes to obtain the second emulsion.

[0070] 3) At room temperature, the organic solvent was removed by rotary evaporation to obtain the product after rotary evaporation. The spin-evaporated product was centrifuged at a ce...

experiment example 1

[0073] This experimental example provides the in vivo distribution of the loaded double-drug nanoparticles prepared in Example 1.

[0074] 20-22 g female BALB / c athymic nude mice were purchased from Beijing Weitong Lihua Experimental Animal Center, Beijing, China. All animal experiments followed the protocols of the Peking University Ethics Committee. By inoculating 1×10 in the armpit of female BALB / c athymic nude mice 7 Three MDA-MB-231 cells were used to establish a triple-negative breast cancer model. When the tumor grows to about 150mm 3 , the mice inoculated with MDA-MB-231 tumors were randomly divided into 4 groups (3 mice in each group). IR780 or NPs / ID were injected into the tail vein respectively (the concentration of IR780 was 100mg / mL). At 3, 5, 8, 12 or 24 hours after administration, the in vivo fluorescence distribution of the mice was recorded using the Maestro small animal fluorescence imaging system. After 24 hours, the mice were killed suddenly, and the t...

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Abstract

The present invention relates to loaded double-drug nanoparticles and its preparation method and application. The loaded double-drug nanoparticles are water-in-oil-in-water nanomicelles, which include amphiphilic polymer PEG‑PPS, hydrophobic drugs and hydrophilic Drugs; prepared by emulsification of amphiphilic polymers, hydrophobic drugs, and hydrophilic drugs. The preparation method of the present invention is simple and easy, and solves the compounding problem of hydrophilic drugs and hydrophobic drugs in the nano-drug loading system, and the double-drug-loaded nanoparticles prepared by the method of the present invention can be detected through the distribution of nanocomposites in vivo, Immunofluorescent staining of tumor tissue, detection of ATP content, detection of ROS active oxygen in vivo, and anti-tumor experiments have shown good photodynamic therapy effects.

Description

technical field [0001] The invention relates to the technical field of drug preparation, in particular to a nanoparticle loaded with double drugs, a preparation method and application thereof. Background technique [0002] Photodynamic therapy as a non-invasive treatment has been widely used in clinical research. Upon laser irradiation, the photosensitizer turns surrounding oxygen molecules into toxic reactive oxygen species that kill tumor cells. However, due to the rapid proliferation of tumor cells and the irregular vasculature of tumor tissue, tumor tissue exhibits hypoxic characteristics, which have great limitations for oxygen-dependent photodynamic therapy. In addition, photodynamic therapy exacerbates hypoxia at the tumor site by directly depleting oxygen or indirectly destroying tumor blood vessels. This in turn affects the therapeutic efficiency of photodynamic therapy. Under hypoxic conditions, cancer cells stimulate HIF-1 expression and regulate a series of si...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K45/06A61K9/107A61K31/65A61K47/32A61P35/00
CPCA61K9/1075A61K31/65A61K41/0057A61K45/06A61K47/32A61P35/00A61K2300/00
Inventor 吴雁赵彩艳王绚
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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