Preparation and application of carrier-free double-drug self-assembled nanoparticles

A self-assembled nanoparticle, carrier-free technology, applied in the field of medicine, can solve the problems of catalysts and organic solvents and other toxic substances residues, complex preparation process, etc., to achieve the effect of improving drug bioavailability, reducing dosage, and improving inhibition

Active Publication Date: 2022-05-13
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in general, nanocarriers such as mesoporous silica are usually obtained through tedious chemical synthesis and modification reactions. Application of medicine system in clinic

Method used

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  • Preparation and application of carrier-free double-drug self-assembled nanoparticles
  • Preparation and application of carrier-free double-drug self-assembled nanoparticles
  • Preparation and application of carrier-free double-drug self-assembled nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Preparation of Ursolic Acid and Sorafenib Carrier-Free Self-Assembled Nanoparticles

[0039] Accurately weigh 8 mg of ursolic acid powder, dissolve it in 2 mL of methanol, and configure it as a 4 mg / mL methanol solution of ursolic acid; accurately weigh 8 mg of sorafenib powder, dissolve it in 2 mL of methanol, and configure it as 4 mg / mL Sorafenib methanol solution; 4 mg / mL ursolic acid methanol solution and 4 mg / mL Sorafenib methanol solution were mixed uniformly according to the volume ratio of 4:1, as the organic phase; Add 0.0625 mL of organic phase dropwise to 1 mL of ultrapure water at a uniform speed, and ultrasonically disperse for 10–20 min at room temperature (25°C), ultrasonic frequency 40 kHz, and ultrasonic power 250 W, and then dry the methanol with a nitrogen blower. The aqueous solution of ursolic acid / sorafenib carrier-free self-assembled nanoparticles was obtained, and the nanoparticles were recorded as nanometer-1.

[0040]Accurately weigh...

Embodiment 2

[0044] Example 2 Observation of appearance and morphology of ursolic acid / sorafenib carrier-free self-assembled nanoparticles

[0045] Take 20 μL of the ursolic acid / sorafenib carrier-free self-assembled nanoparticle aqueous solution prepared in Example 1 and drop it on the surface of fresh mica sheet, and let it stand at room temperature for 30 min, and then wash it three times with ultrapure water to remove Surface impurities were finally blown dry with nitrogen, and images of the nanoparticle surface were collected under an atomic force microscope to confirm the morphology around the sample.

[0046] The result is as figure 2 As shown, the atomic force image results show that the morphology of nano-1, nano-2 and nano-3 is approximately spherical, and the dispersion is good.

Embodiment 3

[0047] Example 3 Stability investigation of ursolic acid / sorafenib self-assembled nanoparticles without carrier

[0048] The ursolic acid / Sorafenib carrier-free self-assembled nanoparticles prepared in Example 1 were dispersed in ultrapure water or in DMEM medium containing 10% fetal bovine serum (FBS) by volume fraction, at 4°C Stored under low temperature, take out an equal volume of nanometer solution every day, measure its particle size with a dynamic light scattering particle size analyzer and record the data.

[0049] The result is as image 3 As shown, the stability results show that when ursolic acid / Sorafenib carrier-free self-assembled nanoparticles are dispersed in ultrapure water and DMEM+10%FBS, the particle size still maintains a relatively stable state, which can be Subsequent cell experiments will provide the experimental basis.

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Abstract

The invention provides a preparation method and application of carrier-free double-drug self-assembled nanoparticles. A chemotherapeutic drug sorafenib and a natural product ursolic acid molecule are self-assembled by a solvent exchange method through a pi-alkyl bond, an alkyl bond and a hydrogen bond to form nanoparticles, then indocyanine green is physically adsorbed into the nanoparticles, and the surfaces of the nanoparticles are modified with nucleic acid aptamers and cell-penetrating peptides, so that the indocyanine green nanoparticles are prepared. Thus, the carrier-free double-drug self-assembled nanoparticles are prepared. Potential toxicity caused by introduction and co-modification of a traditional polymer or inorganic carrier is effectively avoided, and a new way is provided for application of a nanotechnology to the field of cancer treatment.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the preparation and application of carrier-free self-assembled nanoparticles, especially the application in the preparation of drugs for treating liver cancer. Background technique [0002] At present, the clinical treatment of various cancers mainly adopts surgery, radiotherapy and chemotherapy and other treatment methods. Among them, chemotherapy is still the most common treatment method in the treatment of various cancers, and it always occupies an important position. [0003] Sorafenib, as a new type of multi-target anti-tumor drug, is currently the first-line drug approved by the US FDA for the treatment of liver cancer, and has achieved good results in clinical treatment. However, the development process of liver cancer is complicated, and long-term high-dose use can easily lead to drug resistance. A single drug administration strategy can no longer meet the n...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/56A61K47/54A61K47/55A61K47/64A61K49/00A61P35/00B82Y5/00B82Y20/00B82Y40/00A61K31/44
CPCA61K31/44A61K31/56A61K47/55A61K47/549A61K47/64A61K47/6929A61P35/00A61K49/0021A61K49/0052A61K49/0093B82Y5/00B82Y20/00B82Y40/00
Inventor 邵敬伟乐景青杨芳
Owner FUZHOU UNIV
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