Chitosan nanometer ultrasound contrast agent carrying adriamycin and preparation method and application thereof

An ultrasound contrast agent, chitosan nanotechnology, applied in echo/ultrasonic imaging agents, preparations for in vivo tests, medical preparations with non-active ingredients, etc., can solve the research and evaluation of targeting and drug-carrying characteristics and other problems, to achieve high drug encapsulation rate and drug loading, strong imaging ability, and the effect of enhancing development

Active Publication Date: 2019-01-25
SHANDONG UNIV QILU HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the nano-scale ultrasound contrast agent prepared by this method is in the state of nano-droplets. In practical application, certain external stimuli a

Method used

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  • Chitosan nanometer ultrasound contrast agent carrying adriamycin and preparation method and application thereof
  • Chitosan nanometer ultrasound contrast agent carrying adriamycin and preparation method and application thereof
  • Chitosan nanometer ultrasound contrast agent carrying adriamycin and preparation method and application thereof

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Embodiment 1

[0041] Embodiment 1: Preparation of chitosan nanoscale ultrasonic contrast agent carrying DOX

[0042] A preparation method of a chitosan nanoscale ultrasonic contrast agent carrying doxorubicin, the steps are as follows:

[0043] (1) Weigh palmitic acid and lecithin and disperse them in phosphate buffer (Na 2 HPO 4 8mM, KH 2 PO4 2mM, pH7.2), mixing to make a suspension for subsequent use, in the suspension, the concentration of palmitic acid is 0.45g / L, and the concentration of lecithin is 0.9g / L; Add chitosan (molecular weight is 160kDa) and doxorubicin, the concentration of chitosan and doxorubicin in the suspension is respectively 0.5g / L and 1g / L, 25 ℃ co-incubation 30min, obtain the incubation product;

[0044] (2) filling the incubation product prepared in step (1) with perfluoropropane gas, and ultrasonically vibrating for 2 minutes at room temperature to obtain an emulsified product;

[0045] (3) Place the emulsified product prepared in step (2) at 4°C for 2 hour...

Embodiment 2

[0049] A preparation method of a chitosan nanoscale ultrasonic contrast agent carrying doxorubicin, the steps are as follows:

[0050] (1) Weigh palmitic acid and lecithin and disperse them in phosphate buffer (Na 2 HPO 4 8mM, KH 2 PO 4 2mM, pH7.3), mixing to make a suspension for subsequent use, in the suspension, the concentration of palmitic acid is 0.4g / L, and the concentration of lecithin is 0.8g / L; Add chitosan (molecular weight is 160kDa) and doxorubicin, the concentration of chitosan and doxorubicin in the suspension is respectively 0.4g / L and 1.6g / L, 25 ℃ co-incubation 25min, obtain the incubation product;

[0051] (2) filling the incubation product prepared in step (1) with perfluoropropane gas, and ultrasonically vibrating for 3 minutes at room temperature to obtain an emulsified product;

[0052] (3) Place the emulsified product prepared in step (2) at 4°C for 4 hours, remove the lower layer after layering, dilute 6 times and centrifuge at 500rpm at a low spe...

Embodiment 3

[0055] A preparation method of a chitosan nanoscale ultrasonic contrast agent carrying doxorubicin, the steps are as follows:

[0056] (1) Weigh palmitic acid and lecithin and disperse them in phosphate buffer (Na 2 HPO 4 8mM, KH 2 PO 4 2mM, pH7.4), mixing to make a suspension for subsequent use, in the suspension, the concentration of palmitic acid is 0.5g / L, and the concentration of lecithin is 1.0g / L; Add chitosan (molecular weight is 160kDa) and doxorubicin, the concentration of chitosan and doxorubicin in the suspension is respectively 0.6g / L and 1.8g / L, 25 ℃ co-incubation 35min, obtain the incubation product;

[0057] (2) filling perfluoropropane gas into the incubation product obtained in step (1), and ultrasonically vibrating for 4 minutes at room temperature to obtain an emulsified product;

[0058] (3) Place the emulsified product prepared in step (2) at 4°C for 6 hours, remove the lower layer after layering, dilute 8 times and centrifuge at 500rpm at a low spe...

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Abstract

The invention relates to a chitosan nano-level ultrasound contrast agent carrying adriamycin and a preparation method and application thereof, the adriamycin-loaded chitosan nano-level ultrasound contrast agent prepared by the invention Chitosan is use as that shell membrane, Doxorubicin (DOX) and perfluoropropane (PFP) were encapsulated in the chitosan shell membrane, the particle size was 300-900 nm, the average particle size was 641 nm (PDI:0.256). In the nanometer scale, DOX and PFP could penetrate the vascular space of tumor tissues, and had targeting and high efficiency for tumor therapy. The nano-scale ultrasound contrast agent has a strong enhancement imaging ability, but also can maintain the development for a long time, and has higher drug encapsulation efficiency and drug loading, and high biological safety. Combined with ultrasound targeted destruction microbubbles (UTMD) can significantly improve the extraction rate of DOX and reduce the survival rate of tumor cells, whichis conducive to the treatment of tumor diseases.

Description

technical field [0001] The invention relates to a chitosan nanoscale ultrasonic contrast agent carrying doxorubicin, a preparation method and application thereof, and belongs to the technical field of ultrasonic molecular imaging. Background technique [0002] With the rapid development of ultrasound molecular imaging technology and bio-nanotechnology, nanoscale ultrasound contrast agents are developing rapidly. Nano-scale ultrasound contrast agent is one of the research hotspots in the field of molecular imaging in recent years, and it is also one of the important research directions of targeted drug delivery system (TDDS), which can effectively overcome the poor targeting of traditional tumor drugs. , Systemic toxic side effects and other shortcomings. Different from traditional micron-scale ultrasound contrast agents (blood pool imaging agents), nano-scale ultrasound contrast agents have strong penetrating power and can pass through the space between blood vessel walls o...

Claims

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Application Information

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IPC IPC(8): A61K49/22A61K9/51A61K31/704A61K47/36A61K47/12A61K47/24A61P35/00
CPCA61K9/5123A61K9/5161A61K31/704A61K49/223A61P35/00
Inventor 李杰周晓莹郭鲁时丹丹孟冬孙霄商蒙蒙
Owner SHANDONG UNIV QILU HOSPITAL
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