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Cell-specific targeting via nanostructured delivery systems

A nanostructure and carrier system technology, applied in the field of nanostructure carrier systems, can solve problems such as incapability, non-active, non-selective

Active Publication Date: 2021-02-09
智能输送有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage is that not only the desired cells take up the nanoparticles but also other (healthy) cells to which they are transported non-specifically via blood vessels
Another disadvantage is that this transport is restricted by the tumor tissue, i.e. it cannot be transported to other tissues such as kidney or liver
As already mentioned, the disadvantage is that this transport process takes place inactively and nonselectively

Method used

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  • Cell-specific targeting via nanostructured delivery systems
  • Cell-specific targeting via nanostructured delivery systems
  • Cell-specific targeting via nanostructured delivery systems

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0093] Example 1: Synthesis of functionalized polymers

[0094] The synthesized nanoparticles are based on a hydrophobic polymer, poly(lactic-co-glycolic acid) (PLGA), which is biocompatible and biodegradable. This polymer due to its reactive carboxylic acid groups (“acid termination”) can be covalently bonded by coupling agents such as EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) to Conjugates to amine-functionalized dyes. Use polymethine dye DY-635 here (see figure 2 ). Here, every 100th polymer chain is functionalized. Next, the polymer was separated from the free dye DY-635 by dialysis and purified by sedimentation. Here, the characterization is carried out by size exclusion chromatography (SEC), in which a UV / Vis detector and a RI (refractive index) detector are combined with each other. figure 2 A graphical view of the synthesis and the SEC elution profile are shown in .

example 2

[0095] Example 2: Preparation of Nanoparticles

[0096] After functionalization of the polymer (Example 1), nanoparticles were prepared by means of a single emulsion (A) and a double emulsion (B). High-frequency ultrasound is used here, which aids in the formation of nanoscale particles by means of surface-active substances (surfactants, surfactants), here polyvinyl alcohol (PVA). The hydrophobic polymer was for this dissolved in ethyl acetate (25 mg / ml), which is a water-immiscible solvent. 0.3% PVA (polyvinyl alcohol) was used as a surfactant (surfactant) in ultrapure water with a total polymer concentration of 2.5 mg / ml. The polymer suspension in ethyl acetate was added to water with surfactant and nanoparticles were formed by sonication (A). If encapsulating a hydrophilic substance, the hydrophilic substance is first dissolved in water, added to the polymer in ethyl acetate and sonicated. Subsequently, water with surfactant is added to this and nanoparticles are again f...

example 4

[0107] Example 4: Eliciting Drug-Related Effects by RNAi and Absorption in Vitro ("Proof of Concept")

[0108] implement Image 6 A: Hepa 1-6 cells were cultured under standard culture conditions (37°C, 5% CO 2 , DMEM 4.5g / l glucose, 10% heat-inactivated fetal bovine serum, 1% penicillin / streptomycin) were cultured in 6-well plates (100.000 cells / 9.6cm 2 ). After 24 hours, different concentrations of the nanostructured carrier system were added to the wells and incubated for different time periods (concentration and incubation time in Figure 5 Visible in A), the nanostructured carrier system was prepared as in Example 7B. After the incubation time, cells were washed with Hank's balanced salt solution (HBSS) and lysed with RLT buffer (Qiagen GmbH) mixed with 1% β-mercaptoethanol. mRNA was isolated from lysates and analyzed in RT-qPCR. Next, the values ​​were normalized to the expression level of hypoxanthine-guanine-phosphoribosyltransferase and the expression level of HM...

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Abstract

The present invention relates to a nanostructured carrier system comprising at least one polymer and / or at least one lipid and at least one polymethine dye, wherein at least one polymethine dye acts as a target The unit causes the targeted transport of the nanostructured carrier system into the target tissue. The invention also relates to a pharmaceutical composition and the use of the nanostructured carrier system for the transport of the nanostructured carrier system and, if applicable, active pharmaceutical ingredients into target tissues and for the treatment of liver and / or kidney diseases.

Description

technical field [0001] The present invention relates to a nanostructured carrier system comprising one or more polymers and / or lipids and one or more targeting units, especially polymethine dyes, for use in nanostructured carriers The system targets delivery into the target tissue. The invention also relates to the cell-specific transport of one or more pharmaceutical active ingredients into specific target tissues (cell-specific targeting) and the use of the nanostructured carrier system according to the invention for prophylaxis and / or applications for the treatment of disease. Background technique [0002] The use of nanoparticles with conjugated dyes in clinical diagnostics is known in the prior art, for example for detection of organ function or protein expression in the diagnosis of disease-causing states, or for protein histological analysis. Here, coupled dyes, generally fluorescent dyes such as phthalocyanines, are used as labels, the fluorescence and absorption ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K9/127A61K47/34A61K47/22A61K47/10A61K48/00A61K31/713A61K49/00A61K49/06A61K49/22A61P1/16A61P35/00A61P13/12
CPCA61K9/127A61K9/146A61K31/713A61K47/22A61K47/34A61K49/0032A61K49/0084A61K49/0093A61K47/545A61K47/6935A61K47/6911A61K47/6937A61P1/16A61P13/12A61P35/00A61P43/00A61K45/06C12N15/1137C12N2310/14C12N2320/32A61K47/593A61K47/543A61K47/6929
Inventor 迈克尔·鲍尔乌尔里希·舒伯特迈克尔·戈特沙尔特安雅·特雷格克里斯蒂安·皮奇法尔克·根纳特彼得·雷克纳格尔阿德里安·普雷斯
Owner 智能输送有限公司
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