Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A brain-targeted gene delivery system based on polymethacrylate

A polymethacrylate, brain-targeted technology, applied in the biological field, can solve the problems affecting the application potential of gene delivery, and achieve the effects of increasing transfection efficiency and expression level, good application prospects, and controllable degree of modification.

Active Publication Date: 2016-08-03
FUDAN UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it still has a certain hemolytic defect when PDMAEMA is used alone, thus affecting the potential of gene delivery applications

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A brain-targeted gene delivery system based on polymethacrylate
  • A brain-targeted gene delivery system based on polymethacrylate
  • A brain-targeted gene delivery system based on polymethacrylate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] Add 2mmol of methoxy-polyethylene glycol (Me-PEG), 20ml of CH 2 Cl 2 , 1mlTEA, cooled in an ice-water bath, mixed 8.37mol of 2-bromoacetobutyryl bromide with 20ml of CH 2 Cl 2 After mixing, it was slowly added dropwise into a four-neck flask, and the addition was completed in 30 minutes, and reacted at room temperature for 48 hours to generate MPEG-Br.

[0074] In the vacuum reactor A, add the complexing agent bipyridine, vacuumize, under N 2 Add catalyst copper bromide (CuBr) and DMAEMA under protection, magnetically stir, cool with liquid nitrogen, vacuumize - pass N 2 , repeated three times. Initiator (MPEG-Br), solvent isopropanol and water are added to vacuum reactor B, cooled by liquid nitrogen, vacuumed - N 2 , repeated three times. Then melt the contents of the two reactors A and B at room temperature, transfer the initiator solution in B to A with a sampler, cool with liquid nitrogen, evacuate - pass N 2 , repeated three times. Complete the deaeration s...

Embodiment 2

[0079] Dissolve 2.0 mg of the prepared MePEG-PDMAEMA and Maleimide-PEG-PDMAEMA in 0.5ml of deuterated chloroform, identify the structure of the carrier material with a 400MHz superconducting nuclear magnetic resonance spectrometer, and obtain the nuclear magnetic resonance spectrum. The results are shown in the attached figure 1 . After the reaction of PDMAEMA and Me-PEG, the characteristic absorption peak of methoxy group appeared at 3.4ppm, and the characteristic absorption peak of polyethylene glycol appeared at 3.6ppm, indicating that Me-PEG was successfully modified on PDMAEMA (ie MePEG-PDMAEMA) Simultaneously, after PDMAEMA reacted with Maleimide-PEG, in addition to the characteristic absorption peak of polyethylene glycol appeared at 3.6ppm, the characteristic absorption peak of maleimide group also appeared at 6.7ppm, indicating that Maleimide-PEG was successfully connected onto PDMAEMA (ie Maleimide-PEG-PDMAEMA).

Embodiment 3

[0081] Precisely weigh an appropriate amount of lyophilized Maleimide-PEG-PDMAEMA, dissolve it in PBS (pH7.0), and prepare a stock solution with a nitrogen atom concentration of 100nmol / μL; at the same time, prepare a pH7.0 PBS stock solution of the brain-targeting functional group TGN , the concentration is 100nmol / μL containing cysteine. Measure equal volumes of the two stock solutions into vials and stir at room temperature for 4 h. The maleimide group specifically binds to the sulfhydryl group on cysteine ​​to form TGN-PEG-PDMAEMA. Dissolve 2.0mg of the prepared TGN-PEG-PDMAEMA gene delivery carrier in 0.5ml of deuterated chloroform, and identify its structure with a 400MHz superconducting nuclear magnetic resonance spectrometer. The results are shown in the attached figure 1 . After the reaction of Maleimide-PEG-PDMAEMA with brain-targeting functional group TGN, the characteristic absorption peak of maleimide group at 6.7ppm disappeared, indicating that TGN was successf...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention belongs to the field of biotechnology, and relates to a polymethacrylate-based brain-targeted gene delivery system and a preparation method thereof. The carrier of the gene delivery system is composed of three parts covalently linked with the cationic segment polymethacrylate, the electrically neutral segment and the brain-targeting functional group TGN. The carrier then self-assembles with the anionic plasmid DNA through electrostatic interaction to form a nanogel bundle. The invention can deliver the gene drug to pass through the blood-brain barrier and enter the brain to play a role. The invention significantly improves the brain targeting ability of the gene delivery system and the expression of genes in the brain after the administration test by non-invasive intravenous injection; its particle size, surface charge and modification degree of targeting functional groups are all controllable , which facilitates the optimization of gene delivery systems. The gene delivery system constructed by the present invention has the advantages of low cytotoxicity and high brain targeting efficiency.

Description

technical field [0001] The invention belongs to the field of biological technology and relates to a drug delivery system, in particular to a polymethacrylate-based brain-targeted gene delivery system and a preparation method thereof. technical background [0002] With the intensification of population aging process, many brain diseases such as Parkinson's disease and Alzheimer's disease are more and more plagued by human beings, seriously affecting people's health and quality of life. Gene therapy has gradually become a very potential treatment for the above diseases, but due to the existence of the blood-brain barrier (BBB), therapeutic genes cannot autonomously enter the brain lesions and play a therapeutic role. In some studies, hyperosmotic shock, carotid artery injection and direct intracerebroventricular injection were used as invasive routes of administration. Although the effect is good, it is easy to cause brain infection and BBB damage. Therefore, how to increase ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61K47/32A61P25/00
Inventor 张奇志钱勇蒋新国
Owner FUDAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com