Preparation method and application of diagnosis and treatment microbubbles based on Janus drug conjugates

A conjugated and microbubble technology, applied in the field of biomedical materials, can solve the problems of toxic and side effects of organisms, reduce the therapeutic effect, and low drug loading capacity, so as to avoid drug leakage, increase drug loading capacity, and improve enrichment. and the effect of ingestion

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

AI Technical Summary

Problems solved by technology

The above-mentioned drug loading methods have a common disadvantage. The drug loading is low and easy to leak, which reduces the therapeutic effect and easily causes toxic side effects of the organism.

Method used

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  • Preparation method and application of diagnosis and treatment microbubbles based on Janus drug conjugates
  • Preparation method and application of diagnosis and treatment microbubbles based on Janus drug conjugates
  • Preparation method and application of diagnosis and treatment microbubbles based on Janus drug conjugates

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Mix distearoylphosphatidylcholine (DSPC), distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) and Janus drug conjugate (JCFC) according to a certain molar ratio (80%:10 %: 10%), then adopt ethanol injection method, under 50 ℃ of water-bath ultrasonic conditions, inject above-mentioned mixture into 0.8ml water; After 4 hours, 100 μL each of glycerin and propylene glycol were added and mixed evenly. Put the mixed solution into a 3.5mL vial and fill it with a sufficient amount of perfluoropropane (C 3 f 8 ) gas, oscillated by an oscillator for 45s, separated and purified to obtain multifunctional microbubbles (JCFC MBs) integrating ultrasound imaging and chemotherapy. Putting the microbubbles under a fluorescence microscope, it can be observed that the microbubbles present a regular spherical structure with a size between 450nm and 4μm. Under the fluorescence channel, the camptothecin fluorescence on the shell of the microbubbles can be clearly see...

Embodiment 2

[0028] Distearoylphosphatidylcholine (DSPC), distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) and Janus drug conjugate (JCFC) were mixed according to a certain molar ratio (45%:5 %: 50%), then adopt ethanol injection method, under 50 ℃ of water-bath ultrasonic conditions, inject above-mentioned mixture into 0.8ml water; Place the above-mentioned obtained solution in the dialysis bag of molecular weight cut-off 8000-14000Da, dialyze 2~ After 4 hours, 100 μL each of glycerin and propylene glycol were added and mixed evenly. The mixed solution was put into a 3.5mL vial, filled with a sufficient amount of perfluorobutane gas, and oscillated for 45s. After separation and purification, multifunctional microbubbles (JCFC MBs) integrating ultrasound imaging and chemotherapy were obtained. Microbubble size distribution as attached image 3 As shown, the size of the microbubbles is about 0.73um, showing a relatively narrow distribution, indicating that the siz...

Embodiment 3

[0030] Mix distearoylphosphatidylcholine (DSPC), 1,2-dipalmitoyl-sn-glyceryl-3-phosphatidic acid (DPPA) and Janus drug conjugate (JCFC) in a certain molar ratio (45% : 5%: 50%), then adopt the ethanol injection method, under 50 ℃ water bath ultrasonic conditions, inject above-mentioned mixture into 0.8ml water; After 2-4 hours, take it out and add 100 μL each of glycerin and propylene glycol and mix well. The mixture was put into a 3.5mL vial, and enough perfluorooctylbromide was added, and the shaker was shaken for 45s. After separation and purification, multifunctional microbubbles (JCFC MBs) integrating ultrasound imaging and chemotherapy were obtained.

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Abstract

The invention relates to multifunctional microbubbles integrating ultrasonic imaging and chemotherapy, and relates to a preparation method of the multifunctional microbubbles and application of the multifunctional microbbles to tumor diagnosis and treatment. The structure diagram integrating ultrasonic imaging and chemotherapy is shown in the figures, the membrane components of the microbubbles comprise Janus drug conjugates used for chemotherapy and conventional phosphatides, the proportions of the Janus drug conjugates and the conventional phosphatides can be regulated according to needs, and therefore the drug loading capacity is greatly improved. Under an ultrasonic effect, the purpose that designated targeted blasting is converted to nano particles at a tumor site can be achieved through the multifunctional microbubbles, so that the enrichment and uptake of drugs at the tumor site are greatly improved, and the effect of suppressing tumor growth through chemotherapy is greatly improved.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a multifunctional ultrasonic microbubble integrating ultrasonic imaging and chemotherapy, and its application in tumor diagnosis and treatment. Background technique [0002] In 1968, Gramiak reported for the first time the small bubbles that could enhance imaging, that is, ultrasound microbubble contrast agent (UCA), which created a new field of non-invasive ultrasound diagnosis and treatment. With the deepening of its research, it is found that ultrasound microbubble contrast agent is not only a good contrast agent for ultrasound imaging, but also an important drug delivery carrier. Research on ultrasound microbubble contrast agents carrying genes or drug-targeted therapy is becoming more and more extensive in the medical field. Ultrasound microbubble contrast agent-targeted therapy includes ultrasound-mediated drug-loaded microbubble therapy and ultrasound-media...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22A61K31/4745A61K31/7072A61P35/00
CPCA61K31/4745A61K31/7072A61K49/223A61K2300/00
Inventor 戴志飞梁晓龙高闯
Owner PEKING UNIV
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