Construction and application of endoplasmic reticulum targeted nano drug delivery system

A nano-drug loading and endoplasmic reticulum technology, which is applied in nano-drugs, endocrine system diseases, nanotechnology, etc., can solve the problems of inability to deliver active molecules in a targeted manner, and cannot realize carrier functions, etc., and achieve good industrial production and application prospects, design Novel schemes to improve the effect of accumulation

Active Publication Date: 2021-03-12
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

From the above introduction, it can be seen that the research on endoplasmic reticulum-targeted fluorescent probes based on sulfonamide and sulfonylurea groups is relatively mature, but they are only limited to the endoplasmic reticulum localization of their own molecules, and these designs have not been able to realize the carrier Function, unable to deliver active molecules (targets to the endoplasmic reticulum site) that do not have the ability to localize the endoplasmic reticulum to the endoplasmic reticulum

Method used

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  • Construction and application of endoplasmic reticulum targeted nano drug delivery system
  • Construction and application of endoplasmic reticulum targeted nano drug delivery system
  • Construction and application of endoplasmic reticulum targeted nano drug delivery system

Examples

Experimental program
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Effect test

Embodiment 1

[0048] Synthesis of N-dodecyl-4-methylbenzenesulfonamide modification: Weigh dodecylamine and dissolve it in an appropriate amount of dichloromethane (DCM), add triethylamine as an acid-binding agent, weigh and place p-toluene Sulfonyl chloride was dissolved in an appropriate amount of DCM, and slowly added dropwise to the reaction system under stirring in an ice bath. The molar ratio of p-toluenesulfonyl chloride to dodecylamine was 1.2-1.5:1. The reaction was carried out in an ice bath for 1 h, then transferred to room temperature for 4-10 h. During this period, the reaction progress was detected by thin-layer chromatography (TLC), and the system was clear and transparent. After the reaction, the residual triacetic acid was neutralized with 2M dilute hydrochloric acid, the pH was adjusted to neutral by pH test paper, the organic phase was collected after extraction with saturated saline, and the organic solvent was evaporated under reduced pressure in vacuo to obtain a crude ...

Embodiment 2

[0054] Synthesis of p-dodecylbenzenesulfonamide modification: Weigh p-dodecylbenzenesulfonyl chloride, dissolve it in chloroform and add it to a 25mL three-necked flask, add concentrated ammonia water under ice bath conditions, stir magnetically for 30min, and convert to Reaction at room temperature for another 2-6 h, TLC detection of the reaction process. The molar ratio of p-dodecylbenzenesulfonyl chloride to ammonia water is 1:3-10. After the reaction, use chloroform to extract and collect the organic phase, dry it with anhydrous sodium sulfate, filter, collect the organic phase, and evaporate under reduced pressure to remove the organic solvent , to get crude products. Purify by silica gel chromatographic column afterwards, the eluent system is: heptane:ethyl acetate=4:1 (volume ratio), collect target product, evaporate under reduced pressure to remove organic solvent, obtain the target product of purification, it is pale yellow viscous thick liquid, weighed, and calculat...

Embodiment 3

[0060] Synthesis of dodecanesulfonamide modification: first measure ammonia water and add it to a three-necked flask, then add an appropriate amount of methanol, weigh dodecanesulfonyl chloride and dissolve it in an appropriate amount of methanol, slowly add it dropwise under ice-bath stirring conditions, React for 30 minutes, then turn to room temperature and react overnight. After the reaction, use saturated brine and ethyl acetate to extract, collect the organic phase, dry over anhydrous sodium sulfate and filter, then collect the organic phase, and evaporate the organic solvent under reduced pressure to obtain a white crystalline product. Weigh and calculate yield. Store at room temperature or 4°C.

[0061] Dodecylsulfonamide synthesis reaction equation:

[0062]

[0063] Confirmation of dodecanesulfonamide structure: (1) Dodecanesulfonamide was carried out by nuclear magnetic resonance 1 H NMR structure confirmation: 1 H NMR (500MHz, CDCl 3 )δ4.49 (s, 2H), 3.14-3....

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Abstract

The invention provides construction and application of an endoplasmic reticulum targeted nano drug delivery system. By modifying sulfamide or sulfonylurea compounds with endoplasmic reticulum tendencyinto endoplasmic reticulum targeting nano-compounds constructed in a nano-carrier, the constructed novel endoplasmic reticulum targeting liposome can load water-soluble and fat-soluble drugs and quickly transfer the drugs to the endoplasmic reticulum part, so that accumulation of the drugs at the action part of the liposome is improved, and the bioavailability of the drugs is improved. The medicine treatment effect is enhanced, and the toxic and side effect is weakened; the delivery of nucleic acid drugs needing lysosome escape can be remarkably improved, and a new strategy is provided for exerting the curative effect of the drugs. The nano-carrier disclosed by the invention is not only limited to lipidosome, but also can be solid lipid nanoparticles, nano-emulsion, polymer micelles and the like. The endoplasmic reticulum targeted modification nano-carrier provided by the invention is novel in scheme and simple in preparation method, and has good industrial production and applicationprospects.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to the construction of a kind of endoplasmic reticulum targeting nano-drug loading system and its application in the fields of anti-tumor, anti-metabolic disorder, anti-virus and anti-inflammation. Background technique [0002] Drug action targets involve receptors, enzymes, ion channels, transporters, immune system and genes, etc., and drugs need to reach the action targets to exert their efficacy. Modern drug delivery systems require that drugs can be transported to target tissues, target cells, and even specific organelles. At present, the research on tissue and cell-targeted drug delivery systems is relatively mature, and tertiary targeting, that is, organelle targeting, is a hot and difficult point in the current research on drug delivery systems. Tertiary targeting includes cytoplasmic targeting and organelle targeting, and organelle targeting includes mitochondrial targeting, endoplasm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/60A61K45/00C07C303/38C07C311/16A61P5/00A61P29/00A61P35/00B82Y5/00B82Y30/00B82Y40/00
CPCA61K47/6911A61K47/60A61K45/00A61P35/00A61P29/00A61P5/00B82Y5/00B82Y30/00B82Y40/00C07C303/38C07C311/16
Inventor 游剑刘雨
Owner ZHEJIANG UNIV
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