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An oral nanoparticle for penetrating gastrointestinal mucus and epithelial cell barrier and its preparation method and application

An epithelial cell and nanoparticle technology, applied in non-active ingredients medical preparations, medical preparations containing active ingredients, pharmaceutical formulas, etc., can solve the problem of weakening the affinity between nanocarriers and cell membranes, the effect is not satisfactory, and the real Solve problems such as effective drug delivery

Active Publication Date: 2022-08-02
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, it is worth noting that the modification of hydrophilic PEG weakens the affinity between nanocarriers and cell membranes, making them lack the ability to overcome the two barriers of intestinal mucus diffusion layer and epithelial cell absorption layer at the same time, and cannot really solve the problem of nanocarriers entering the gastrointestinal tract. The problem of effective drug delivery after drug delivery, the effect of improving drug oral absorption is still unsatisfactory

Method used

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  • An oral nanoparticle for penetrating gastrointestinal mucus and epithelial cell barrier and its preparation method and application
  • An oral nanoparticle for penetrating gastrointestinal mucus and epithelial cell barrier and its preparation method and application
  • An oral nanoparticle for penetrating gastrointestinal mucus and epithelial cell barrier and its preparation method and application

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Embodiment 1

[0041] A preparation method of oral nanoparticles for penetrating gastrointestinal mucus and epithelial cell barrier, characterized in that, comprising the following steps:

[0042] (1) Preparation of pH-responsive materials, the synthesis process is as follows figure 1 shown:

[0043] A: Dissolve 2.50 g of stearic acid (SA) in 100 ml of dichloromethane (DCM), add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to the above solution (EDCI) 2.02g, triethylamine (TEA) 1ml and tert-butyl carbazate (boc-hydrazide) 1.39g, reacted at room temperature for 12h, after the reaction, washed with water 3 times, then washed with saturated brine 3 times, It was then dried over anhydrous sodium sulfate, filtered, and the solvent was removed in vacuo to obtain 2.77 g of BOC-protected hydrazide SA;

[0044] B: Dissolve 1 g of BOC-protected hydrazide SA in 20 mL of ethyl acetate, add 2 drops of hydrochloric acid dropwise to the above solution, and react at room temperature for 2 h...

Embodiment 2

[0049] A preparation method of oral nanoparticles for penetrating gastrointestinal mucus and epithelial cell barrier, characterized in that, comprising the following steps:

[0050] (1) Preparation of pH-responsive materials:

[0051] A: Dissolve 1.10 g of stearic acid (SA) in 30 mL of dichloromethane (DCM), and add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to the above solution (EDCI) 1.48g, triethylamine (TEA) 0.2mL and tert-butyl carbazate (boc-hydrazide) 0.61g, react at room temperature for 20h, after the reaction, wash with water 3 times, then with saturated brine 3 times , then dried over anhydrous sodium sulfate, filtered, and the solvent was removed in vacuo to obtain 1.31 g of BOC-protected hydrazide SA;

[0052] B: Dissolve 0.50 g of BOC-protected hydrazide SA in 15 mL of ethyl acetate, add 3 drops of hydrochloric acid dropwise to the above solution, and react at room temperature for 4 h. After the reaction, the product is washed with deionized wat...

Embodiment 3

[0057] A preparation method of oral nanoparticles for penetrating gastrointestinal mucus and epithelial cell barrier, characterized in that, comprising the following steps:

[0058] (1) Preparation of pH-responsive materials:

[0059] A: 1.50 g of stearic acid (SA) was dissolved in 20 mL of dichloromethane (DCM), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was added to the above solution (EDCI) 1.72g, triethylamine (TEA) 0.2mL and tert-butyl carbazate (boc-hydrazide) 1.04g, react at room temperature for 24h, after the reaction, wash with water 3 times, then with saturated brine 3 times , then dried over anhydrous sodium sulfate, filtered, and the solvent was removed in vacuo to obtain 1.76 g of BOC-protected hydrazide SA;

[0060] B: Dissolve 0.50 g of BOC-protected hydrazide SA in 20 mL of ethyl acetate, add 3 drops of hydrochloric acid dropwise to the above solution, and react at room temperature for 6 h. After the reaction, the product is washed with de...

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Abstract

The invention discloses a preparation method of oral nanoparticles for penetrating gastrointestinal mucus and epithelial cell barrier, comprising the following steps: (1) preparing a pH-responsive material: combining polyethylene glycol and stearic acid through an acylhydrazone bond Connect to obtain a pH-responsive material; (2) prepare a polymer material: connect the chitosan oligosaccharide and stearic acid through an amide bond to obtain a polymer material; (3) prepare a nanoparticle: combine the pH-responsive material of the above step (1). It is mixed with the polymer material of step (2), and a nano-coprecipitation self-assembly method is adopted to obtain a core / shell oral nanoparticle with the polymer material as the core and the pH-responsive material as the shell. In the nanoparticles obtained by the preparation method provided by the invention, the acylhydrazone bonds are broken and the polyethylene glycol shell is broken off in the mucus microenvironment, and the CSO-SA inner core is exposed, so as to realize the transition from hydrophilicity to hydrophobicity and near neutrality to positive charge on the surface of the nanoparticles Transition and increased adhesion, which in turn enhances its ability to cross the epithelial cell barrier, improve the oral absorption rate of the drug.

Description

technical field [0001] The invention relates to the field of drug carrier materials, in particular to an oral nanoparticle for penetrating gastrointestinal mucus and epithelial cell barriers, and a preparation method and application thereof. Background technique [0002] Currently, the gastrointestinal biological barrier is the main reason for the low oral bioavailability of drugs. Although the encapsulation of the drug by nanocarriers can protect it from degradation by gastrointestinal enzymes, for the drug to be effectively absorbed into the blood circulation, the nanocarriers must pass through the mucus diffusion barrier on the intestinal surface and the epithelial cell absorption barrier successively. The highly viscoelastic and dynamically renewed mucus layer has a strong ability to capture and rapidly remove exogenous particles, which is an important barrier for the diffusion of nanocarriers to epithelial cells for further absorption. The force (cell membrane affinity...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/16A61K47/26A61K47/36A61K38/28A61P3/10A61K9/50C08B37/08C08G65/333
CPCA61K47/16A61K47/26A61K47/36A61K38/28A61P3/10A61K9/5031C08B37/003C08G65/33324
Inventor 张金洁李建波张振中强弘王帅帅冯天歌蔡慧杰刘志磊
Owner ZHENGZHOU UNIV
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