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Gadolinium and copper sulphide loaded polyethyleneimine nanometer gel as well as preparation and application thereof

A polyethyleneimine and nanogel technology, which can be applied to preparations for in vivo tests, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., can solve the problems of poor effect of nanodiagnostic agents and other problems

Active Publication Date: 2019-04-05
DONGHUA UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is to provide a polyethyleneimine nanogel loaded with gadolinium and copper sulfide and its preparation method and application, so as to overcome the defects of poor efficacy of nano-diagnostic agents in the prior art

Method used

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  • Gadolinium and copper sulphide loaded polyethyleneimine nanometer gel as well as preparation and application thereof
  • Gadolinium and copper sulphide loaded polyethyleneimine nanometer gel as well as preparation and application thereof
  • Gadolinium and copper sulphide loaded polyethyleneimine nanometer gel as well as preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] (1) Dissolve 272mg polyethyleneimine (PEI) and 32mg N,N-methylenebisacrylamide (BIS) in 5mL ultrapure water, mix and stir for 15min, then add dropwise to 60mL Span 80 in toluene ( 20mg / mL), stirred at 1000rpm for 30min to initially form a W / O emulsion, and then placed the W / O emulsion in a sonicator for 2min sonication, then added 1.2mL triethylamine dropwise and continued to stir at 1000rpm overnight. Afterwards, the W / O emulsion was centrifuged at 12000rpm for 15min, and the supernatant was removed. The precipitate was redispersed with 15mL of methanol and placed in a 8-10kDa dialysis bag for dialysis for 3 days to obtain PEI NGs.

[0069] (2) Dissolve 27.5mg FA in 5mL DMSO, then add 3mL of EDC in DMSO (3.25mg / mL) and 2mL of NHS in DMSO (3mg / mL) to activate for 3h. Then 5mL NH 2 - PEG-COOH DMSO solution (10 mg / mL) was added dropwise to the above-mentioned activated solution, stirred for 3 days, dialyzed (PBS 1d, ultrapure water 2 days), and freeze-dried to obtain FA-...

Embodiment 2

[0072] The PEI NGs, FA:Gd@PEI NGs and FA:CuS:Gd@b-PEI NGs solutions (500 μg / mL) prepared in Example 1 were used to measure the surface potential and hydrodynamic diameter. The measurement results (Table 1) showed that the surface potential of PEI NGs was +53.3mV and the hydrodynamic diameter was 532.7nm. While FA:CuS:Gd@b-PEI NGs exhibited a decreased surface potential (+10.2 mV) and a reduced hydrodynamic diameter (258.5 nm). The successful synthesis of FA:CuS:Gd@b-PEI NGs was demonstrated. At the same time, the hydrodynamic diameter of FA:CuS:Gd@b-PEI NGs in various solutions (water, saline, PBS, DMEM) is almost unchanged, which proves that FA:CuS:Gd@b-PEI NGs has good colloidal stability sex. The FTIR spectra of PEI NGs prepared in Example 1 and FA:CuS:Gd@b-PEI NGs were measured afterwards ( image 3 ), 1651cm in the spectrum of PEI NGs -1 The absorption peak at shows the presence of carbon-oxygen double bonds in the cross-linking agent BIS. 1591cm in the spectrum of F...

Embodiment 3

[0076] The content of Gd element in the FA:CuS:Gd@b-PEI NGs prepared in Example 1 was determined by the ICP-AES test method. FA:CuS:Gd@b-PEI NGs with Gd concentration of 0.05, 0.1, 0.2, 0.3 and 0.4mM and 2mL aqueous solution of gadolinium agent Magnevist were prepared respectively, and the magnetic resonance imaging analyzer was used to measure the material's concentration at different Gd concentrations. T 1 relaxation effects (such as Figure 7 ). The calculated r of FA:CuS:Gd@b-PEI NGs and clinical gadolinium agent Magnevist 1 The values ​​are 11.66 and 4.56mM respectively -1 the s -1 . r of FA:CuS:Gd@b-PEI NGs 1 higher than the r of the clinical gadolinium agent Magnevist 1 value. It shows that the FA:CuS:Gd@b-PEI NGs prepared in Example 1 can be used as excellent T in MR molecular imaging diagnosis. 1 Positive contrast agent.

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Abstract

The invention relates to gadolinium and copper sulphide loaded polyethyleneimine nanometer gel as well as preparation and application thereof. The gel contains folic acid, DTPA-Gd compounds, 1,3-propane sultone, copper sulphide and polyethyleneimine nanometer gel. The preparation method comprises the following steps of preparing polyethyleneimine gel; preparing a gadolinium, folic acid and amphoteric ion modified polyethyleneimine nanometer gel compound; preparing gadolinium and copper sulphide loaded polyethyleneimine nanometer gel. The gel has the uniform dimension distribution; good solution dispersion performance and cell compatibility are realized; the r1 relaxation rate is obviously improved; good photothermal conversion efficiency is realized; the potential application value is realized in the fields of MR imaging and PTT.

Description

technical field [0001] The invention belongs to the field of nano therapeutic agent and its preparation and application, in particular to polyethyleneimine nanogel loaded with gadolinium and copper sulfide and its preparation method and application. Background technique [0002] Magnetic resonance (MR) imaging technology is an advanced medical imaging diagnostic technology developed in the 1970s, and has been widely used in the detection and early diagnosis of various human diseases. MR imaging has high resolution, high spatial and tomographic imaging capabilities, no ionization damage caused by radiation, and can obtain anatomical and physiological information at the same time, which has incomparable advantages in other medical imaging. MR imaging is playing an increasingly important role in the field of disease surveillance. However, the weakness of MR imaging is its low sensitivity, and the overlapping relaxation times of different organs or tumor tissues make MR imaging...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/34A61K47/22A61K49/18A61K49/12A61K41/00A61P35/00
CPCA61K9/06A61K41/0052A61K47/22A61K47/34A61K49/105A61K49/12A61K49/1803A61P35/00
Inventor 史向阳张昌昌孙文杰徐放夏进东王玥
Owner DONGHUA UNIV
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