Double-drug loaded nanoparticle and preparation method and application thereof

A nanoparticle and nanomicelle technology, which is used in pharmaceutical formulations, drug combinations, antitumor drugs, etc., can solve problems such as insufficient response to drug stimulation, achieve good photodynamic therapy effects, and the preparation method is simple and feasible. effect of the problem

Active Publication Date: 2018-12-25
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the heterogeneity of tumors, the ROS-med

Method used

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  • Double-drug loaded nanoparticle and preparation method and application thereof
  • Double-drug loaded nanoparticle and preparation method and application thereof
  • Double-drug loaded nanoparticle and preparation method and application thereof

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 invention relates to a double-drug loaded nanoparticle and a preparation method and application thereof. Being a water-in-oil-in-water nanomicelle, the double-drug loaded nanoparticle comprising amphiphilic polymers PEG-PPS (polyethylene glycol-polyphenylene sulfite), hydrophobic drugs and hydrophilic drugs is prepared through the emulsification reaction of the amphiphilic polymers, hydrophobic drugs and hydrophilic drugs. The preparation method of the double-drug loaded nanoparticle is simple and easy to apply and solving the problem of compounding the hydrophilic drugs and hydrophobic drugs in a nano drug delivery system. Furthermore, the double-drug loaded nanoparticle prepared through the preparation method has the advantages of passing various detection such as distribution detection of nano-components in vivo, immunofluorescence staining of tumor tissues, detection of ATP (adenosine triphosphate) content, detection of ROS (reactive oxygen species) in vivo and anti-tumor experiments and exhibiting a good photodynamic therapy effect.

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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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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