Preparation of medicine-carrying nano particles transmitting blood brain barrier and application of nano particles in cooperation with focused ultrasonic targeted micro-bubble damage technology

A blood-brain barrier and drug-loaded nanotechnology, applied in the field of biomedicine, can solve the problems of curcumin hindrance and poor stability

Active Publication Date: 2019-07-30
PEKING UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is difficult to pass through the blood-brain barrier, which has become an obstacle for the application of curcumin in vivo and clinical treatment.
[0003] With regard to the methods used by nanoparticles as chemotherapeutic drug carriers to pass through the blood-brain barrier, the most widely used surface modification is polysorbate 80, which can adsorb apolipoproteins ApoB and ApoE in plasma to its surface, and use ApoB, ApoE can bind to low-density lipoprotein receptors on the capillary endothelial cells in the brain, and through receptor-mediated endocytosis, it can enter the brain tissue and release drugs through the blood-brain barrier, but its biggest disadvantage is its relatively low stability. Poor, can cause premature drug release before reaching the target site

Method used

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  • Preparation of medicine-carrying nano particles transmitting blood brain barrier and application of nano particles in cooperation with focused ultrasonic targeted micro-bubble damage technology
  • Preparation of medicine-carrying nano particles transmitting blood brain barrier and application of nano particles in cooperation with focused ultrasonic targeted micro-bubble damage technology
  • Preparation of medicine-carrying nano particles transmitting blood brain barrier and application of nano particles in cooperation with focused ultrasonic targeted micro-bubble damage technology

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] According to curcumin and N, N-di-hexadecyl-Nα-6-(3-triethoxysilyl) propyl dimethylaminocaproyl-L-alaninamide in a molar ratio of 1:15 Organic / inorganic complex lipids in chloroform (CHCl 3 ) and mix well. Using the film hydration method, the above system was evaporating in a water bath at 55° C. for 15-30 minutes until the solvent was completely evaporated to form a film. Add 5% polysorbate 80 deionized aqueous solution, hydrate the film in a 55°C water bath for 15-30 minutes, and use an ultrasonic pulverizer at 20% strength for 10 minutes to fully disperse it. The resulting system was left overnight at 4°C until it self-assembled to form curcumin nanoparticles, and centrifuged at 6000 rpm to remove unencapsulated free curcumin. The nanoparticle structure of the system is uniform and stable, and the particle diameter is about 110 nanometers observed by transmission electron microscope and atomic force microscope. Specific as figure 2 shown.

Embodiment 2

[0024] Mix distearoylphosphatidylcholine (DSPC) and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) in a molar ratio of 1:9, and then use the ethanol injection method to sonicate in a water bath at 50°C. Under certain conditions, the above mixture was injected into 0.8 ml of water; the solution obtained above was placed in a dialysis bag with a molecular weight cut-off of 8000-14000 Da, and dialyzed for 2-4 hours, and after taking it out, 100 microliters of glycerin and propylene glycol were added and mixed evenly. Put the mixed solution into a 3.5ml vial, fill it with a sufficient amount of perfluoropropane gas, and vibrate with an oscillator for 30 seconds. After separation and purification, microbubbles for targeted destruction by focused ultrasound are obtained. The size of the microbubbles is between 0.5- 2 microns, showing a relatively narrow distribution, and the size of the surface microbubbles is relatively uniform. Specific as image 3 sho...

Embodiment 3

[0026] In order to evaluate the effect of polysorbate 80-modified siliceous nanoparticles and microbubbles in Example 1-2 on opening the blood-brain barrier in the targeted destruction of focused ultrasound, the mice were fixed in a stereotaxic apparatus, and polysorbate was injected intravenously. Sorbitol 80-modified siliceous nanoparticles and microbubbles at a concentration of 2 × 10 5 One per gram of body weight, and adopt the acoustic parameter conditions of a center frequency of 1.28MHz and an ultrasonic sound pressure of 0.6MPa, and act for 1 minute. Then at 0.1, 6, 12 and 24 hours, the mice were perfused with normal saline and fixed with 4% paraformaldehyde, the brain tissue was separated, and the content of curcumin in the three-dimensional brain tissue was observed by fluorescence imaging using the Caliper Spectrum IVIS imaging system and quantitative. Specific results such as Figure 4As shown, group 1 is the normal saline control group, group 2 is the curcumin c...

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Abstract

The invention relates to medicine-carrying nano particles transmitting the blood brain barrier and cooperating with a focused ultrasonic targeted micro-bubble damage technology for assisting a chemotherapeutic drug curcumin in transmitting the blood brain barrier and relates to a preparation method and effective parameters of a drug conveying system and application of the drug conveying system intreatment for the neurodegenerative disease. The schematic diagram of the medicine-carrying nano particles transmitting the blood brain barrier and cooperating with the focused ultrasonic targeted micro-bubble damage technology is shown in the description, carrier components comprise organic / inorganic compound lipid and polysorbate 80, the proportion can be regulated and controlled according to the demands, the medicine-carrying amount is increased, the plasma half-life is prolonged, and the efficiency of transmitting the blood brain barrier is improved. Under the function of the focused ultrasonic targeted micro-bubble damage, through the nano particles, the curcumin can be gathered and taken in the specific brain area through a fixed-point and targeted method, and the treatment effect ofthe chemotherapy on the neurodegenerative disease is effectively improved.

Description

technical field [0001] The invention belongs to the field of biomedical technology, and specifically relates to a drug delivery system that combines drug-loaded nanoparticles through the blood-brain barrier combined with focused ultrasound targeted microbubble destruction technology, and its use in central nervous degenerative diseases. Background technique [0002] The blood-brain barrier refers to the barrier between plasma and brain cells formed by the walls of brain capillaries and glial cells, and the barrier between plasma and cerebrospinal fluid formed by the choroid plexus, which can prevent viruses, bacteria and other toxins from being released from the blood Enter the brain tissue, but also block the delivery of most drugs, for example, curcumin has shown potential in different experimental models to treat Parkinson's, and can clear the wrongly accumulated α-synuclein in the striatum . However, the difficulty of crossing the blood-brain barrier has become an obsta...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K31/12A61K41/00A61K47/54A61P25/28
CPCA61K31/12A61K41/0023A61K2300/00
Inventor 戴志飞张妮丝郑海荣
Owner PEKING UNIV
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