GA/Fe2+ nanoparticles, composite nanoparticles thereof, preparation and application

A nanoparticle and reaction solution technology, applied in the field of medicine, can solve the problems of aseptic inflammation of acidic degradation products, the initial burst release aggravates neurotoxicity, and the inability to significantly increase drug loading, so as to promote Fenton reaction and avoid brain tissue edema , Improve the effect of bioavailability

Active Publication Date: 2020-07-14
SHANDONG UNIV QILU HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although Wafer has received more and more attention, but the inventors found that the slow-release chemotherapy system has exposed some defects in clinical application, such as: ①The drug loading is single and the drug loading cannot be significantly increased. If the drug loading is increased, it will lead to initial breakthrough ②Some patients may have obvious local cerebral edema; ③Acidic degradation products can easily cause aseptic inflammation; ④Degraded debris may block the circulation of cerebrospinal fluid

Method used

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  • GA/Fe2+ nanoparticles, composite nanoparticles thereof, preparation and application
  • GA/Fe2+ nanoparticles, composite nanoparticles thereof, preparation and application
  • GA/Fe2+ nanoparticles, composite nanoparticles thereof, preparation and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1 GA / Fe 2+ Preparation of nanoparticles

[0050] FeCl 2 4H 2 O (23 mg) and PVP (80 mg) were added to 4 ml of degassed deionized water, and after stirring vigorously at room temperature for 5 minutes, GA (1 ml, 10 mg ml) dissolved in deionized water -1 ) was added dropwise into the above solution and stirred in a nitrogen atmosphere. After 24 hours, a purple GA / Fe 2+ nanocomposites. Concentrate and purify by ultrafiltration using an ultrafilter with a molecular weight cut off (MWCO) of 10 kDa. The resulting nanoparticles were stored at 4°C. GA / Fe 2+ The preparation process and function of nanoparticles are shown in figure 1 shown.

Embodiment 2

[0051] Example 2 GA / Fe 2+ Preparation of @ZIF-8 nanoparticles

[0052] This embodiment uses ZIF-8 package GOX and GA / Fe 2+ Granules, including: GA / Fe to be formulated with deionized water 2+ Nanoparticles (prepared by Example 1) solution (15mg ml -1 ) was added dropwise with stirring 160mM Zn(NO 3 ) 2 ·6H 2O aqueous solution, after stirring for 5 minutes, the mixed solution was added dropwise to 10 mM 2-methylimidazole aqueous solution under vigorous stirring, and the reaction solution was centrifuged for 10 minutes, and the obtained precipitate was washed with water for 3 times.

[0053] Among them, GA / Fe 2+ SEM and TEM images of @ZIF-8 nanoparticles figure 2 As shown, the particle size distribution and average particle size are as follows image 3 , Figure 4 As shown, the zeta potential is as Figure 5 shown.

Embodiment 3

[0054] Example 3 Drug-loaded GA / Fe 2+ @ZIF-8 nanoparticles

[0055] 1. GOX+GA / Fe 2+ Preparation of @ZIF-8 nanoparticles

[0056] GA / Fe prepared with deionized water 2+ Nanoparticles (prepared by Example 1) solution (15mg ml -1 ) was added dropwise with stirring 160mM Zn(NO 3 ) 2 ·6H 2 In O aqueous solution, the Zn(NO 3 ) 2 ·6H 2 GOX was dissolved in O aqueous solution, and the concentration of GOX was 1 mg / mL. After stirring for 5 minutes, the mixed solution was added dropwise to 10 mM 2-methylimidazole aqueous solution under vigorous stirring, and the reaction solution was centrifuged for 10 minutes, and washed with water. The resulting precipitate was 3 times.

[0057] Among them, GOX+GA / Fe 2+ SEM and TEM images of @ZIF-8 nanoparticles figure 2 As shown, the particle size distribution and average particle size are as follows image 3 , Figure 4 As shown, the zeta potential is as Figure 5 shown.

[0058] 2. DOX+GOX+GA / Fe 2+ Preparation of @ZIF-8 nanopart...

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Abstract

The invention provides GA / Fe2+ nanoparticles, composite nanoparticles thereof, preparation and application. The GA / Fe2+ nanoparticles comprise or are obtained by compounding the following raw materials: Fe2+ salt, PVP and GA. ZIF-8 is adopted to encapsulate the GA / Fe2+ nanoparticles and carry drugs such as DOX and / or GOX to obtain the composite nanoparticles, the content of iron ions in tumor cells can be remarkably increased, meanwhile, in combination with the carried drugs, a synergistic effect on tumor killing is achieved, a Fenton reaction is promoted, tumor cell iron death is induced, andtherefore, growth of the tumor cells is effectively inhibited.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a GA / Fe 2+ Nanoparticles, their composite nanoparticles, preparation and applications. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Glioma is a cancer of the central nervous system with a high degree of malignancy and high local recurrence. Local chemotherapy has become one of the most promising methods for the treatment of glioma due to its definite therapeutic effect and small systemic side effects, and has been recognized by the latest edition of the United States. It is recommended by the NCCN guidelines, but it has not yet been clinically applied in China. The only local sust...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/52A61K47/22A61K47/12A61K47/61A61K47/69A61K33/26A61K31/704A61K38/44A61P35/00
CPCA61K9/5123A61K47/61A61K47/6929A61K33/26A61K31/704A61K38/44A61P35/00C12Y111/01A61K2300/00
Inventor 倪石磊张玉霖仲瀚林戚其超
Owner SHANDONG UNIV QILU HOSPITAL
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