Liposome-encapsulated organic-metal-framework nano medicine delivery system preparation method and application

A nano drug delivery system, organometallic technology, applied in the field of preparation of liposome-encapsulated organometallic framework nano drug delivery system, can solve problems such as DNA single-strand breaks, DNA base damage, programmed cell death, etc., to increase Oxidative stress levels, good stability, and low toxicity to normal cells

Inactive Publication Date: 2019-01-04
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The increased reactive oxygen species (ROS) can cause DNA base damage and a large number of DNA single-strand breaks (SSB) and lead to programmed cell death

Method used

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  • Liposome-encapsulated organic-metal-framework nano medicine delivery system preparation method and application
  • Liposome-encapsulated organic-metal-framework nano medicine delivery system preparation method and application
  • Liposome-encapsulated organic-metal-framework nano medicine delivery system preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Preparation and characterization of MOF-Fe with different particle sizes in Example 1

[0038] The organic ligand solution and the iron compound were magnetically stirred under heating, and then part of the reaction solution was taken out from the flask. Continue to add organic ligand solution and iron compound solution to the original reaction solution, and take out part of the reaction solution after reacting for a period of time. Continue with the same steps. The reaction solution taken out at different stages was washed and dried in vacuum. MOF-Fe with different particle sizes were obtained.

[0039] The molar ratio of the initial organic ligand solution to the iron compound is 5:1-1:1.

[0040] The molar ratio of the added organic ligand solution to the iron compound solution is 5:1-1:1.

[0041] The reaction time is 15min-4h.

[0042]The morphology of the three different particle size products was observed by scanning electron microscope (SEM), and the 50nm p...

Embodiment 2

[0044] Example 2 Preparation and characterization of Lip / MOF-Fe nano drug delivery system

[0045] The mass ratio is 40%-70% of phospholipid, 15%-30% of cholesterol, and 5%-20% of DSPE-mPEG dissolved in chloroform and methanol. Add a certain volume of MOF-Fe absolute ethanol solution to the above mixed solution. 37 ° C water bath, vacuum rotary evaporation to remove the organic solvent to form a uniform film. Add 0.05-0.3mM dichloroacetic acid solution and hydrate under vacuum for 30min. The obtained solution was placed in an ice bath, and the cell sonicator was sonicated for 1-15min, 10-30KHz, 100-300W. Then, the polycarbonate membrane (pore size: 400 nm, 200 nm, 100 nm) was repeatedly extruded sequentially through a small extruder. The obtained product was separated and purified by G50 Sephadex column. The particle size and particle size distribution were measured by Malvern laser particle size analyzer, and the morphology was observed by TEM.

[0046] The phospholipid ...

Embodiment 3

[0048] Example 3 Lip / MOF-Fe long-term stability and serum stability evaluation

[0049] For long-term stability evaluation, Lip / MOF-Fe was prepared into 1.0mg / ml with PBS solution, stored at 4°C and 25°C, and the particle size was measured with a dynamic light scattering instrument (DLS), once every two days. Continuous measurement for two weeks to investigate the long-term stability of nanoparticles. For evaluation of serum stability, Lip / MOF-Fe was formulated with PBS containing 50% fetal bovine serum (FBS) to a concentration of 1.0 mg / ml. At 37°C, the particle size change was detected at different time points.

[0050] Such as Figure 5 As shown, the stability of the nanoparticles is good, and the particle size has no significant change (p>0.05) after being placed for 2 weeks; the serum stability results are as follows: Figure 6 As shown, the nano drug delivery system did not agglomerate, and the particle size did not change significantly (p>0.05). Good stability.

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Abstract

The invention discloses a liposome-encapsulated organic-metal-framework nano medicine delivery system preparation method and application. An organic metal framework is MOF-Fe prepared from an iron compound and an organic ligand, is octahedral morphologically and has mimetic peroxidase catalytic activity. Water solubility can be improved by PEC modified liposome encapsulation, and dichloroacetic acid solution in pH of 4.0 is loaded into liposome to provide acidic catalytic reaction conditions for MOF-Fe, so that the liposome-encapsulated organic-metal-framework nano medicine delivery system isfinally formed. The medicine delivery system is characterized in that the particle size is about 150nm, spherical shape, high stability, high catalytic activity and slowness in release are realized, and hydroxyl radicals and superoxide anions are continuously generated through reaction with H2O2. Internal oxidative stress level of tumor cells can be raised, tumor cell apoptosis is induced, and remarkable suppression effects on tumor tissues are achieved. Therefore, a novel scheme is provided for antitumor treatment such as tumor non-chemotherapeutic pharmaceutical treatment and multi-drug resistance of tumors.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis and nano preparations, in particular to a preparation method and application of a liposome-wrapped organometallic framework nano drug delivery system. Background technique [0002] Tumor cells have the ability of unlimited growth, proliferation, new blood vessels, invasion and metastasis, which is the same as H 2 o 2 production is closely related. Tumor cells produce excess H through glucose metabolism 2 o 2 , and is strictly regulated by various stimuli such as cells, cytokines and growth factors. h 2 o 2 Mainly produced by mitochondria, as a nonpolar molecule, H 2 o 2 It can freely pass through the cell membrane and nuclear membrane, activate different signaling pathways, and have special effects on the proliferation, differentiation, migration or apoptosis of tumor cells. tumor cells to H 2 o 2 Has a strong dependence and is also very sensitive to its changes, H 2 o 2 To...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/24A61P35/00
CPCA61K9/1271A61K47/24A61P35/00
Inventor 孙磊陈建美郭雷雷王学堃徐郁蕊高雅张继康张瑜蒙霞葛俊良宁兴海
Owner NANJING UNIV
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