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A reduction-responsive drug-loaded nanoparticle and its preparation method and use

A drug-loaded nano-responsive technology, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of being pumped out of the cell

Inactive Publication Date: 2018-08-28
HEFEI UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the release of drugs from traditional nanocarriers is generally achieved by passive diffusion, and the released drugs may be further pumped out of the cell.

Method used

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  • A reduction-responsive drug-loaded nanoparticle and its preparation method and use
  • A reduction-responsive drug-loaded nanoparticle and its preparation method and use
  • A reduction-responsive drug-loaded nanoparticle and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1: Amphiphilic copolymer mPEG 45 -b-P(DssEEP 15 -EEP 20 )Synthesis

[0036] Polyethylene glycol-polyphosphate is composed of phosphate monomer EEP, DssEEP in the initiator PEG 2K Under the initiation of , TBD is obtained by ring-opening polymerization as a catalyst, and the synthetic route is as follows figure 1 shown.

[0037] 1. Preparation of phosphate monomer

[0038] First, 2-chloro-2-oxo-1,3,2-dioxaphospholane (2-chloro-2-oxo-1,3,2-dioxaphospholane, COP), then COP reacts with ethanol to synthesize EEP, and COP reacts with 2-hydroxyethyl dodecyl persulfide to synthesize DssEEP. Concrete synthetic method is as follows:

[0039] Synthesis of COP: In a 1000mL three-necked round-bottomed flask, dissolve phosphorus trichloride (3.0mol) in anhydrous dichloromethane (500mL), and slowly drop in ethylene glycol (3.0mol) through a constant pressure dropping funnel , after all the drops are finished, continue to react for 0.5 hours, evaporate the solvent under...

Embodiment 2

[0044] Example 2: Amphiphilic copolymer mPEG 45 -b-P(DssEEP 12 -EEP 6 )Synthesis

[0045] Polyethylene glycol-polyphosphate is composed of phosphate monomer EEP, DssEEP in the initiator PEG 2K Under the initiation of , TBD is obtained by ring-opening polymerization as a catalyst, and the synthetic route is as follows figure 1 shown.

[0046] 1, the preparation process of phosphate monomer is the same as embodiment 1.

[0047] 2. Synthesis of block polymers

[0048] The reaction was carried out in a glove box. The reaction was carried out in a glove box. Dissolve mPEG (100g, 0.05mol, Mn=2000g / mol), cyclic phosphate ester monomer DssEEP (0.6mol) and EEP (0.3mol) in THF (10L) (mPEG: DssEEP: EEP molar ratio is 1 :12:6), stir and mix evenly, add catalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD, 0.1mol), react at 25°C for 3min, add benzoic acid ( 0.2mol) to terminate the reaction; the resulting product was precipitated twice in a mixed solvent of ether and methanol (10 / 1, ...

Embodiment 3

[0049] Embodiment 3: Characterization of amphiphilic copolymer PEG-b-P (EEP-DssEEP)

[0050] The polyethylene glycol-polyphosphate block copolymer that embodiment 1,2 prepares carries out proton nuclear magnetic resonance spectrum ( 1 H NMR) analysis to determine its molecular structure and link number, 1 H NMR spectrum see figure 2 .

[0051] figure 2 of polyethylene glycol-polyphosphate 1 H NMR spectrum letters label the protic hydrogens assigned to the block polymer. Through the peak of 3.75ppm (assigned to the methylene group of polyethylene glycol), the peak of 4.31ppm (assigned to the methylene group of the PEEP side chain) and the peak of 2.96ppm (assigned to the methylene group of the PDssEEP side chain) The integral area ratio is calculated to obtain the number of phosphate linkages.

[0052] Gel Permeation Chromatography (GPC) method takes polyethylene glycol as the GPC collection of illustrative plates of the polyethylene glycol-polyphosphate block copolymer...

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Abstract

The invention discloses a drug-loaded nanoparticle with reductive responsiveness and a preparation method and applications thereof. The structural formula of the drug-loaded nanoparticle with reductive responsiveness is as follows:, wherein x is 45, y is 15, and z is 20, or x is 45, y is 12, and z is 6. The diameter of the drug-loaded nanoparticle disclosed by the invention is 91-109 nm. PEG hydrophilic segments constitute a hydrophilic shell layer of the polymer nanoparticle, and polyphosphoesters of which a side group contains disulfide bonds constitute a hydrophobic core. The block polymer can be formed into a micelle by self-assembling in water, and then pharmaceutical molecules are loaded in the hydrophobic core of the carrier nanoparticle through a physical embedding effect, so that the drug solubility is greatly increased, the cycling time is prolonged, and the vascular permeability enhancement effect (i.e. enhanced permeability and retention EPR effect enhancement) is passively targeted to tumor tissues. The nano drug carrier can entrap various hydrophobic antineoplastic drugs such as hydrophobic drugs such as doxorubicin, paclitaxel, gefitinib, camptothecin, and the like.

Description

1. Technical field [0001] The invention relates to a drug-loaded nanoparticle, in particular to a reduction-responsive drug-loaded nanoparticle and its preparation method and application. 2. Background technology [0002] Currently, the main method for treating tumors is chemotherapeutics (chemotherapy). However, the effect of chemotherapy is not satisfactory. Especially with the progress of chemotherapy, tumor cells gradually develop resistance to chemotherapy drugs (including multidrug resistance, MDR), which leads to the failure of clinical chemotherapy. Current studies have shown that most MDR tumor cells have overexpressed P-glycoprotein (P-gp) in their cell membranes, which can excrete anticancer drugs out of the cell. Therefore, how to circumvent the role of P-gp is an important problem to be solved urgently to overcome the drug resistance of such tumor cells. [0003] Nanoparticles based on polymer materials are widely used as delivery carriers for chemotherapy dr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/51A61K9/107A61K47/34A61K31/704A61P35/00
Inventor 杨显珠曹紫洋马寅初钱海生陶伟
Owner HEFEI UNIV OF TECH
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