A nano-drug delivery system based on low-generation pamam dendrimer loaded with disulfiram and photosensitizer indocyanine green and its application

A technology of indocyanine green and dendrimer, which is applied in the directions of non-active ingredient medical preparations, active ingredients-containing medical preparations, drug combinations, etc., can solve the complex reaction process, high production cost and low yield. problems, to achieve the effect of improving metabolism too fast, reducing dosage, and increasing action time

Active Publication Date: 2021-06-29
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the application of PAMAM is still mainly based on drug carriers. For example, patent CN201410271351 discloses a folic acid-PAMAM-ursolic acid nano drug with tumor targeting. The initial materials used in this nano drug are highly toxic G3 and G5 To replace polyamide-amine dendrimers (PAMAM), the amino groups on the surface of PAMAM need to be replaced with hydroxyl groups to reduce the toxicity of the material itself, and then folic acid and ursolic acid are reacted with the hydroxyl groups on the surface of PAMAM to finally synthesize the target product. The reaction process is complicated, the production cost is high, and the yield is not high, which limits its application to a certain extent

Method used

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  • A nano-drug delivery system based on low-generation pamam dendrimer loaded with disulfiram and photosensitizer indocyanine green and its application
  • A nano-drug delivery system based on low-generation pamam dendrimer loaded with disulfiram and photosensitizer indocyanine green and its application
  • A nano-drug delivery system based on low-generation pamam dendrimer loaded with disulfiram and photosensitizer indocyanine green and its application

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Experimental program
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Effect test

preparation example Construction

[0036] Preparation of IDG nano drug delivery system

[0037] At room temperature, 10 mg of PAMAM-G0 was added dropwise to 1.7 mL of water, and after ultrasonication for 0.5 h, 100 µL of a certain mass of DSF-DMSO solution and 200 µL of a certain mass of ICG-DMSO solution were simultaneously added dropwise to the above solution After continuous ultrasonication for 4 h, the solution was taken out, placed in a dialysis bag with a molecular weight of 500, and dialyzed in water for 24 h to remove unloaded DSF and solvent DMSO, and freeze-dried to obtain nanomedicine.

[0038] Particle size and potential analysis and detection of DSF@G0 nanomedicine with different DSF contents

[0039] Table 1 The particle size and potential distribution of DSF @G0 nanoparticles with different ICG contents

[0040]

[0041] Particle size and potential analysis and detection of IDG nanomedicine with different ICG content

[0042] Table 2 Particle size and potential distribution of IDG nanoparticle...

Embodiment 1

[0046] Determination of Particle Size and Potential of IDG Nano Drug Delivery System

[0047] IDG samples were prepared according to the optimal drug-carrier ratio after screening (by mass ratio, G0:DSF:ICG=20:4:1), and 1 mg of prepared IDG powder was dissolved in 1 mL of a mixed solvent (ethanol: water = 1:9), after ultrasonication for 15 minutes, dilute 10 times to measure the particle size and potential in the Malvern particle size analyzer, the results are as follows Figure 1a with 1b As shown, the particle size of the IDG nano drug delivery system prepared according to the optimal carrier-to-drug mass ratio is 149.5 nm, less than 200 nm, which is in line with the particle size suitable for the EPR effect, and the charge is 3.75 mV, which is positively charged and can be used with Negatively charged cell membranes fuse into the interior of the cell.

Embodiment 2

[0049] Atomic force microscopy of IDG nano drug delivery system

[0050] Take 20 µL of the prepared IDG solution and drop it on the surface of the mica sheet used for atomic force microscope photography. Nanomorphology, the result is as figure 2 As shown, the nanoparticles are evenly distributed on the whole plane, and the particle size is about 50 nm, which is smaller than the particle size measured by the particle size analyzer. Because the atomic force microscope is more precise and accurate, the captured nanoparticles are more accurate, so the particle size is smaller than the particle size. The particle size measured by the diameter meter.

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Abstract

The invention belongs to the technical field of biopharmaceuticals, and specifically relates to the preparation of a nano drug delivery system based on low-generation PAMAM dendrimers loaded with the classic "alcohol withdrawal drug" disulfiram and photosensitizer indocyanine green and its application in the field of anti-tumor . Based on the low-generation dendrimer PAMAM-G0, the present invention uses a solvent exchange method to pack disulfiram DSF and indocyanine green ICG into the low-generation dendrimer PAMAM-G0 to prepare an IDG nano drug delivery system. The nano drug delivery system prepared by the present invention can be enriched in the tumor site through the EPR effect, and then play the role of chemotherapy and photodynamic therapy under the condition of light, reduce the tissue toxicity of chemotherapy drugs and the phototoxicity of photodynamic therapy, and is an anti-cancer drug for disulfiram. Cancer therapy provides a new research direction.

Description

technical field [0001] The present invention builds a stable and reliable nano drug delivery system IDG with uniform particle size distribution based on the low-generation dendritic macromolecule PAMAM (G0), and delivers new anticancer drugs (classic "alcohol withdrawal drugs") disulfiram and photosensitizer indole Cyanine green to the tumor site, combined with the chemotherapy effect of disulfiram and the photodynamic effect of indocyanine green to kill cancer cells and treat cancer, specifically involves the construction of IDG nano drug delivery system and anti-tumor research, which belongs to the field of biopharmaceutical technology. Background technique [0002] Disulfiram (Disulfiram, DSF), also known as disulfiram, is the most common alcohol withdrawal drug, and its structural formula is as follows: [0003] ; It can effectively inhibit the activity of acetaldehyde dehydrogenase (ALDH) and block the oxidative metabolism of acetaldehyde. Recent studies have shown th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K9/19A61K47/34A61K31/145A61P35/00
CPCA61K9/19A61K31/145A61K41/0057A61K47/34A61P35/00A61K2300/00
Inventor 邵敬伟沈志春廖羽琴周敏
Owner FUZHOU UNIV
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