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Unsaturated fatty acid-photosensitizer co-assembled nanoparticles and their construction methods and applications

A technology of unsaturated fatty acids and photosensitizers, applied in the application field of anti-tumor drug delivery system, can solve the problems of unfavorable development, poor biocompatibility, cumbersome synthesis, etc., and achieve the effect of reducing adverse reactions and toxicity

Active Publication Date: 2022-07-01
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the polymer used as the carrier has the characteristics of cumbersome synthesis, residual organic solvent and poor biocompatibility, which is not conducive to the further development of the combined application of UFA-photosensitizer

Method used

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  • Unsaturated fatty acid-photosensitizer co-assembled nanoparticles and their construction methods and applications
  • Unsaturated fatty acid-photosensitizer co-assembled nanoparticles and their construction methods and applications
  • Unsaturated fatty acid-photosensitizer co-assembled nanoparticles and their construction methods and applications

Examples

Experimental program
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Effect test

Embodiment 1

[0046] Example 1: Preparation of PEG-modified TAPP-OA co-assembled nanoparticles

[0047] OA, TAPP and PEG modifier DSPE-PEG 2000 Dissolved in DMSO to prepare 8.3 mg / mL OA stock solution, 5 mg / mL TAPP stock solution and 1.0 mg / mL DSPE-PEG, respectively 2000 stock solution. Combine 50 μL OA stock, 50 μL TAPP stock and 50 μL DSPE-PEG 2000 The stock solution was mixed (the molar ratio of oleic acid and photosensitizer was 4:1), and the mixed solution was added dropwise to 2 mL of deionized water at a stirring speed of 800 rpm to form nanoparticles spontaneously. Transfer the preparation to an ultrafiltration tube and centrifuge at 3000 rpm for 15 minutes to remove the organic solvent in the preparation, and add deionized water to the desired concentration. The particle size and morphology of the PEG-modified TAPP-OA co-assembled nanoparticles prepared in this example were observed using a transmission electron microscope. The results are shown in figure 2 A; The particle siz...

Embodiment 2

[0048] Example 2: Preparation of PEG-modified TAPP-LA co-assembled nanoparticles

[0049] LA, TAPP and PEG modifier DSPE-PEG 2000 Dissolved in DMSO to prepare 16.6 mg / mL LA stock solution, 10 mg / mL TAPP stock solution and 2.0 mg / mL DSPE-PEG, respectively 2000 stock solution. Combine 50 μL LA stock, 50 μL TAPP stock and 100 μL DSPE-PEG 2000 The stock solution was mixed (the molar ratio of linoleic acid and photosensitizer was 4:1), and the mixed solution was added dropwise to 4 mL of deionized water at a stirring speed of 900 rpm to form nanoparticles spontaneously. Transfer the preparation to an ultrafiltration tube and centrifuge at 3000 rpm for 15 minutes to remove the organic solvent in the preparation, and add deionized water to the desired concentration. The particle size and morphology of the PEG-modified TAPP-LA co-assembled nanoparticles prepared in this example were observed using a transmission electron microscope. The results are shown in image 3 A; Dynamic lig...

Embodiment 3

[0050] Example 3: Preparation of PEG-modified TAPP-LNA co-assembled nanoparticles

[0051] LNA, TAPP and PEG modifier DSPE-PEG 2000 Dissolved in DMSO to prepare 33.2mg / mL LNA stock solution, 20mg / mL TAPP stock solution and 4.0mg / mL DSPE-PEG, respectively 2000 stock solution. Combine 100 μL NA stock, 100 μL TAPP stock and 100 μL DSPE-PEG 2000 The stock solution was mixed (the molar ratio of linolenic acid and photosensitizer was 4:1), and the mixed solution was added dropwise to 10 mL of deionized water at a stirring speed of 1000 rpm to form nanoparticles spontaneously. Transfer the preparation to an ultrafiltration tube and centrifuge at 3000 rpm for 15 minutes to remove the organic solvent in the preparation, and add deionized water to the desired concentration. The particle size and morphology of the PEG-modified TAPP-LNA co-assembled nanoparticles prepared in this example were observed using a transmission electron microscope. The results are shown in Figure 4 A; The ...

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Abstract

The unsaturated fatty acid-photosensitizer co-assembled nanoparticle and its construction method and application belong to the field of new auxiliary materials and new dosage forms for pharmaceutical preparations. Preparation method: Dissolve a certain amount of a mixture of unsaturated fatty acid, photosensitizer and PEG modifier into an appropriate amount of organic solvent, slowly drop the solution into deionized water under stirring conditions, and spontaneously form uniform nanoparticles. The particle size of the obtained nanoparticles is small and uniform, which is conducive to the enrichment of nanoparticles in the tumor site through the enhancement effect of penetration and retention; it has an ultra-high drug loading capacity, which is beneficial to reduce the adverse reactions and toxicity related to excipients; Using a photosensitizer, the combined use of linoleic acid and tetrakis (4-aminophenyl) porphyrin can significantly increase the level of intracellular lipid peroxidation and thus the most significant increase in ROS level, resulting in a synergistic anti-tumor effect.

Description

technical field [0001] The invention belongs to the field of new excipients and new dosage forms for pharmaceutical preparations, and particularly relates to co-assembled nanoparticles of unsaturated fatty acids and photosensitizers, a construction method thereof, and applications in antitumor drug delivery systems. Background technique [0002] Cancer is a major disease that seriously threatens human life and health. According to the World Health Organization (WHO), more than 8 million people die of cancer every year in the world. Currently, common cancer treatment strategies are surgical resection, chemotherapy, radiation therapy, and phototherapy. Compared with other therapies, photodynamic therapy is favored by patients and medical staff due to its less systemic toxicity and high treatment selectivity. During photodynamic therapy, photosensitizers can be activated by external specific wavelengths to generate reactive oxygen species (ROS), especially singlet oxygen ( 1 ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K41/00A61K47/54A61K47/60A61P35/00A61K31/201A61K31/202
CPCA61K47/542A61K47/60A61K41/0071A61K9/145A61P35/00A61K31/201A61K31/202A61K2300/00
Inventor 孙进侯彦先何仲贵
Owner SHENYANG PHARMA UNIVERSITY