Polycation capable of being degraded into spermine, and synthesis method and nanoparticles thereof

A technology of polycation and synthesis method, which is applied in the fields of polycation degradable to spermine and its synthesis and nanoparticle, can solve the problems of loss of spermine and non-degradation, etc.

Inactive Publication Date: 2012-06-27
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the degradation of these two polycations is achieved through the breakage of the linker. The C-N-C bond between the spermine and the linker cannot be degraded, and the spermine cannot return to the original state but has fragments of the linker after the breakage. thus losing the significance of spermine as an endogenous molecule

Method used

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  • Polycation capable of being degraded into spermine, and synthesis method and nanoparticles thereof
  • Polycation capable of being degraded into spermine, and synthesis method and nanoparticles thereof
  • Polycation capable of being degraded into spermine, and synthesis method and nanoparticles thereof

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Experimental program
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Effect test

Embodiment 1

[0037] The synthetic method of Polyimine-PSP

[0038] Such as figure 1 Shown, the synthetic route of polycation. The whole reaction is carried out in an anhydrous and oxygen-free environment. Weigh a certain amount of spermine, add an appropriate amount of newly steamed ethanol to dissolve (add an appropriate amount of dry molecular sieves simultaneously), then weigh aceglyoxal (40w% aqueous solution) according to a suitable stoichiometric ratio, and store it at -10~10°C (preferably 0 °C), methylglyoxal (40w% aqueous solution) was slowly added dropwise to the above mixture. Then react overnight at room temperature at 10-30°C. Filtrate, dialyze the filtrate in deionized water for 10-48 hours with a dialysis bag (Mw=7000), freeze-dry at low temperature and remove water in a vacuum to obtain the final product.

[0039] The H-NMR spectrum of Polyimine-MSP is as follows figure 2 Shown; The IR spectrum of Polyimine-MSP is shown as image 3 shown by figure 2 , 3 It can be s...

Embodiment 2

[0041] Polyimine-MSP in vitro degradation experiment

[0042] The GPC chromatographic columns involved in the present invention are water Ultrahydrogel water-soluble gel columns, which are respectively Ultrahydrogel 120 model WAT011520 and Ultrahydrogel 250 model WAT011525. The detector is a differential viewer. Size exclusion chromatography (equipped with a differential monitor) tests the relative molecular weight of polycations degraded under physiological conditions. This method uses 1-4% formic acid aqueous solution as mobile phase, and the flow rate is 0.6-1ml / min. First dissolve the polycation in pure water to prepare a 2mg / ml aqueous solution, then use dilute hydrochloric acid to adjust the pH value of the polycation aqueous solution to 7.4, then incubate at 37°C, and take samples at regular intervals for molecular weight testing. The result is as Figure 4 shown by Figure 4 It can be seen that within two hours, the molecular weight of the polymer did not change gre...

Embodiment 3

[0044] Preparation of polyimine-MSP and plasmid-forming complex polyplex

[0045] Preparation of complexes. Detection of polycation (Polyimine-MSP) as a gene carrier complexes DNA or RNA through electrostatic interaction under different mass ratios with DNA or RNA. Weigh quantitative polycations, add ultrapure water or DEPC water to make a 2mg / mL solution, then filter with a 0.22μm sterile filter head, dilute the plasmid concentration to 1mg / mL, and prepare complex solutions with different mass ratios , it is necessary to keep the concentration of the plasmid solution constant, then dilute the concentration of the polycation solution according to different mass ratios, pay attention to keep the volumes of the diluted polycation solution and the plasmid solution equal, and finally quickly add the polycation solution to the plasmid solution and mix , and incubated at room temperature for 15-30min, thus obtaining a series of complexes with mass ratio.

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Abstract

The invention discloses a polycation capable of being degraded into spermine, and a synthesis method and nanoparticles thereof, belonging to the technical field of medicines. The polycation can be used for conveying nucleic acids. Spermine and pyruvaldehyde are utilized to construct and degrade the polycation returningto the initial state of multi-ammonia molecules. The synthesis method of the polycation comprises the following steps: slowly dropwisely adding a pyruvaldehyde water solution into a spermine ethanol solution, and simultaneously adding the mixture into a dry molecular sieve; and stirring with a magnetic stirrer at room temperature to carry out condensation reaction on primary amino group, aldehyde group and keto-carbonyl group. The polycation is degradable, and can release spermine containing unprotonated amino group in the degradation process; and the degradation product can not generate acidic group like other degradable polymers. The polycation is beneficial to lysosome escape, and also beneficial to releasing genes in cytoplasm with low surface charges. As for the proton sponge effect, the lysosome cracks due to the osmotic pressure generated by the proton sponge effect. The amino key of the polycation has the action of proton sponge.

Description

technical field [0001] The present invention relates to a synthesis method in the field of pharmaceutical technology, in particular to a polycation that can be used for nucleic acid (DNA and RNA) delivery, with spermine as the basic building block and degradable to spermine, and its synthesis method, nano particles. Background technique [0002] Effective gene delivery requires the delivery system to be able to complete a series of biological functions, including compressing genes into compact particles, delivering genes to target cells, helping genes escape lysosome degradation, and releasing genes into the cytoplasm , self-degrades to non-toxic monomers and can be eliminated in vivo. To meet these requirements, a synthetic gene delivery vehicle should structurally contain functional groups to achieve the above biological functions. In order to simplify the preparation process and toxicity test, the simplicity of the structure of the synthetic gene carrier is very importa...

Claims

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Application Information

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IPC IPC(8): C08G73/00C12N15/87C12N15/85
Inventor 杜子秀金拓黄立群
Owner SHANGHAI JIAO TONG UNIV
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