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Functionalized mesoporous silica tumor targeted transportation controlled-release system and preparation method thereof

A tumor targeting, mesoporous silicon technology, applied in antitumor drugs, powder delivery, drug delivery, etc., can solve the inaccuracy of the evaluation carrier system, the difficulty of clinical trials, and the inability of the drug delivery system to achieve targeting, etc. problem, to achieve the effect of high drug utilization, reducing agglomeration and increasing dispersibility

Active Publication Date: 2019-03-01
HUBEI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The research on polylysine / cyclodextrin / mesoporous silicon drug carrier has made some progress in drug release control, but there are still many problems: (1) polylysine / cyclodextrin / mesoporous silicon drug carrier system The research belongs to bioengineering, which is subject to objective conditions, and it is difficult to conduct clinical trials in a short period of time. These results cannot fully and truly reflect the situation of human trials, so it brings a lot of inaccuracy to the evaluation of the carrier system
(2) Due to the complexity of the tumor microenvironment, the drug delivery system cannot achieve better targeting

Method used

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  • Functionalized mesoporous silica tumor targeted transportation controlled-release system and preparation method thereof
  • Functionalized mesoporous silica tumor targeted transportation controlled-release system and preparation method thereof
  • Functionalized mesoporous silica tumor targeted transportation controlled-release system and preparation method thereof

Examples

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Effect test

Embodiment 1

[0056] 1. Preparation of p-toluenesulfonyl-β-cyclodextrins (β-CD-OTs)

[0057] Weigh 25g of β-CD and dissolve it in 300mL of 0.4M NaOH solution, and stir in an ice-water bath until the cyclodextrin is completely dissolved. 18 g of p-toluenesulfonyl chloride (TsCl) was weighed and slowly added dropwise to the β-CD solution. After stirring and reacting in an ice-water bath for 90 min, suction filtration was performed. The filtrate was taken, and the pH was adjusted to 8.5 with HCl. The mixture was stirred and reacted at room temperature for 2 h, and the reactant was placed in the refrigerator (4° C.) overnight, and suction filtered the next day, and the filter residue was washed three times with deionized water. The final product was dried at 60 °C to obtain β-CD-OTs.

[0058] 2. Preparation of nitrogenated cyclodextrin (β-CD-N3)

[0059] Weigh 10g of β-CD-OTs and dissolve in 100mL of deionized water, heat to 80°C, then add 2.54g of sodium azide (NaN3), and stir for 18h. The...

Embodiment 2

[0084] 1. Preparation of p-toluenesulfonyl-β-cyclodextrins (β-CD-OTs)

[0085] Weigh 25g of β-CD and dissolve it in 350mL of 0.4M NaOH solution, and stir in an ice-water bath until the cyclodextrin is completely dissolved. 20 g of p-toluenesulfonyl chloride (TsCl) was weighed and slowly added dropwise to the β-CD solution. After stirring and reacting in an ice-water bath for 90 min, suction filtration was performed. The filtrate was taken, and the pH was adjusted to 8.5 with HCl. The mixture was stirred and reacted at room temperature for 2 h, and the reactant was placed in the refrigerator (4° C.) overnight, and suction filtered the next day, and the filter residue was washed three times with deionized water. The final product was dried at 60 °C to obtain β-CD-OTs.

[0086] 2. Preparation of nitrogenated cyclodextrin (β-CD-N3)

[0087] Weigh 10g of β-CD-OTs and dissolve in 100mL of deionized water, heat to 80°C, then add 3.22g of sodium azide (NaN3), and stir for 18h. The...

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Abstract

The invention provides a functionalized mesoporous silica tumor targeted transportation controlled-release system and a preparation method thereof. Cyclodextrin is used for coating mesoporous silica,and further coating poly-lysine; amino amidation treatment is performed to obtain a system with high medicine carrying and release controlling. A preparation process comprises preparation of p-toluenesulfonyl-beta-cyclodextrin, preparation of nitriding cyclodextrin, synthesis of S-(2-aminoethylmercapto)-2-mercaptopyridine hydrochloride, preparation of mercapto functionalized mesoporous silica nanoparticles, preparation of disulfide functionalized mesoporous silica nanoparticles, preparation of alkynyl functionalized mesoporous silica nanoparticles, preparation of medicine-carrying mesoporous silica nanoparticles, preparation of amantadine-terminated poly-lysine, wrapping modification of poly-lysine, and amino amination modification. By adopting the preparation method, the targeted enriching and release of medicaments is realized finally, and high medicament utilization rate is achieved.

Description

technical field [0001] The invention relates to the field of drug controlled release, in particular to the field of a functionalized mesoporous silicon tumor targeted transport controlled release system and a preparation method thereof. Background technique [0002] In recent years, with the research on the tumor microenvironment, people have gradually realized that the tumor microenvironment is a highly heterogeneous micro-ecosystem composed of tumor cells and their surrounding environment, which is constantly evolving with the development of tumors. Compared with normal tissues and blood circulating in the body, tumor tissues have a lower pH (pH≈6.8), and endosomes and intracellular lysosomes exhibit lower pH values ​​(<5.4) and higher concentrations of GSH. Therefore, pH- and reduction-sensitive carriers are widely used. [0003] The cell membrane is a phospholipid bilayer, which means that constructing a negatively charged or uncharged carrier can reduce the phagocy...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/64A61K47/61A61K31/704A61P35/00
CPCA61K31/704A61K47/61A61K47/645A61K47/6923A61P35/00
Inventor 李草陈重银罗毕矗卢金博万立辉陈辉
Owner HUBEI UNIV
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