Lipid nano granule containing magnetic resonance contrast agent as well as preparation method and use thereof

A magnetic resonance contrast agent and lipid nanoparticle technology, which is applied in the directions of MRI/MRI contrast agent, emulsion delivery, drug delivery, etc., can solve the problem of distinguishing intestinal contents, low detection rate of small lesions, Difficulty and other problems to achieve the effect of improving the encapsulation rate

Active Publication Date: 2009-08-05
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The first method has a low detection rate for small lesions, and it is difficult to distinguish small lesions of mucosal origin from intestinal contents
The second method is better than the first method for lesion detection and lesion characterization. However, after intravenous administration, it is distributed throughout the body without tissue and organ targeting and specificity. It is distributed in the intercellular space and cannot enter the cell. Distribution

Method used

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  • Lipid nano granule containing magnetic resonance contrast agent as well as preparation method and use thereof
  • Lipid nano granule containing magnetic resonance contrast agent as well as preparation method and use thereof
  • Lipid nano granule containing magnetic resonance contrast agent as well as preparation method and use thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1～3

[0023] Embodiments 1-3 are related to the preparation method of loaded Gd-DTPA lipid nanoparticles

Embodiment 1

[0024] Embodiment 1: Preparation of loaded Gd-DTPA lipid nanoparticles

[0025] Weigh 200mg of Span-80 and dissolve in 10mL of n-hexane to form the organic phase of the emulsion; in addition, weigh the prescription amount of Gd-DTPA and 18mg of Tween-80 recorded in Table 1, dissolve in 1mL of distilled water to form the aqueous phase . Under the stirring condition of 400rpm, the aqueous phase is added in the organic phase to form a water-in-oil (W / O) microemulsion; 50 mg of the glycerol monostearate and lecithin mixture of the recipe amount are weighed and dissolved in 1 mL of absolute ethanol, The solution was quickly poured into 11 mL of W / O microemulsion, and stirred continuously for 5 min at room temperature to obtain a lipid nanoparticle dispersion system. The dispersion system was centrifuged at a high speed of 20000rpm to separate the precipitated lipid nanoparticles, washed the precipitated lipid nanoparticles twice with 2mL of n-hexane, and dispersed the precipitated...

Embodiment 2

[0028] Example 2: Investigation of the physicochemical properties of the loaded Gd-DTPA lipid nanoparticles (note: the consistency of the effect and the weight 4 ratio)

[0029]Take an appropriate amount of the lipid nanoparticle dispersion prepared above, dilute it 20 times with 0.1% poloxamer solution, and measure its particle size and surface potential with a 3000HS particle size and surface potential analyzer.

[0030] The encapsulation efficiency of Gd-DTPA in nanoparticles was determined and calculated by indirect method. Nanoparticles are prepared as described above, the lipid nanoparticle dispersion is centrifuged after adding hydrochloric acid flocculation, the supernatant is collected, and the fluorescence spectrophotometry (Ex=495nm, Em=514nm, Slit=5nm) measures the fluorescence value I 1 , calculate the amount of free Gd-DTPA in the solution; Calculate the encapsulation efficiency of fluorescent graft by (1) formula:

[0031]

[0032] Gd-DTPA drug loading is ca...

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Abstract

The invention provides a lipid nano-particle which is easy to absorb by an intestinal tract, wherein a magnetic resonance contrast agent, namely gadolinium diethylenetriaminepentaacetic acid (Gd-DTBA) is loaded, and glyceryl monostearate and lecithin are taken as lipid materials. The invention applies lipidosome nano-particles which are easy to absorb by the intestinal tract to enveloping the magnetic resonance contrast agent, namely the gadolinium diethylenetriaminepentaacetic acid which is clinically used most commonly to ensure that the magnetic resonance contrast agent, namely the gadolinium diethylenetriaminepentaacetic acid which is not absorbed by a digestive canal can be absorbed into an intestinal wall in a large quantity to make the intestinal wall produce MRI enhancement, displays pathological changes through the difference of normal intestinal walls and the pathological changes on the absorption and distribution of the lipid nano-particle, and can reflect the absorption function condition of the lipid nano-particle caused by the pathological changes. The method has the following advantages: the local administration is performed, and no intravenous and systemic administration are needed; the method may realize the evaluation of an intestinal absorption function; the nano-particle enters cells to realize the horizontal visualization of the cells; and the nano-particle mainly adopts lymph transport and can realize lymphatic imaging which are favorable for the lymphatic target display of intestinal pathological changes.

Description

technical field [0001] The invention relates to a lipid nanoparticle loaded with a magnetic resonance contrast agent, a preparation method thereof and an application in intestinal magnetic resonance imaging. Background technique [0002] Various imaging methods, including barium double contrast radiography, CT, and MRI, all play an important role in the examination of intestinal lesions. The various positive contrast agents involved, such as barium, iodine-containing contrast, and gadopentetate meglumine (Gd-DTPA), are not easily absorbed or cannot be absorbed by the digestive tract. Compared with CT, MRI has extremely high soft tissue resolution and no radiation, so it has attracted much attention in the examination of intestinal lesions in recent years. The most widely used clinical MR contrast agent is Gd-DTPA. Gd-DTPA is a positive contrast agent and is not absorbed by the digestive tract. There are two main methods of its application in the digestive tract. The firs...

Claims

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Application Information

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IPC IPC(8): A61K49/06A61K49/18
Inventor 章士正袁弘孙继红胡富强郑伟良杜永忠
Owner ZHEJIANG UNIV
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