Self-assembled nano medicine-loaded micelle as well as preparation method and application thereof

A nano-drug loading and self-assembly technology, which is applied in the direction of pharmaceutical formulations, anti-tumor drugs, drug combinations, etc., can solve the problems of not being able to identify anti-tumor drugs, and achieve the effect of inhibiting proliferation and division, particle size and fractional coefficient.

Inactive Publication Date: 2020-02-21
YUNNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have found that tetrandrine (TET) can specifically bind to P-gp and change the configuration of P-gp so that its active site cannot recognize anti-tumor drugs to reverse multidrug resistance

Method used

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  • Self-assembled nano medicine-loaded micelle as well as preparation method and application thereof
  • Self-assembled nano medicine-loaded micelle as well as preparation method and application thereof
  • Self-assembled nano medicine-loaded micelle as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] The present embodiment provides a kind of preparation method of paclitaxel dimer, and this preparation method comprises the following steps:

[0057] 1.1 Weigh 136mg (0.16mmol) PTX and dissolve it in 5mL dichloromethane (DCM);

[0058] 1.2 Add 18.7mg (0.089 mmol) DTDP, and then sequentially add 67.1mg (0.35 mmol) 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) and 2.2 mg (0.018 mmol) 4-dimethylaminopyridine (DMAP);

[0059] 1.3 Stir at 20°C for 50-90min at a speed of 600rpm;

[0060] 1.4 Then add 32.1mg (0.17 mmol) EDC.HCl and 2.2mg (0.018 mmol) DMAP in sequence, and continue to stir for 20-30 hours under nitrogen protection;

[0061] 1.5 Use TLC spot plate to detect the reaction process; the reaction product is purified by silica gel column chromatography, using dichloromethane (DCM): ethyl acetate (EA) = 2:1 as the mobile phase, and using a rotary evaporator (30°C) to remove excess PTX after liquid 2 .

[0062] by NMR 1 H-NMR and UHPLC-Orbi...

Embodiment 2

[0064] This embodiment provides the preparation of blank non-drug-loaded blank nanomicelles. The nanomicelles in this embodiment are preferably mPEG-PLGA blank nanomicelles. The preparation method includes the following steps:

[0065] 1.1 Weigh 10 mg of the carrier material mPEG-PLGA and dissolve it in 4 mL of tetrahydrofuran (THF) solution;

[0066] 1.2 Add this solution drop by drop to 10mL of vigorously stirred deionized water, control the drop rate to 15s / drop, and continue to stir for 48h after the dropwise addition;

[0067] 1.3 Use a rotary evaporator at 35°C for 20 minutes to remove unvolatilized THF;

[0068] 1.4 Centrifuge the solution at 5000rmp for 5min to remove mPEG-PLGA that does not form micelles;

[0069] 1.5 Take the supernatant and dialyze it through a dialysis membrane with a molecular weight of 3500~10000 to remove the residual organic solvent again, which is the mPEG-PLGA blank nanomicelle solution.

Embodiment 3

[0071] This embodiment provides a preparation method of self-assembled nano drug-loaded micelles, the preparation method comprising the following steps:

[0072] 1.1 Weigh 10mg of PTX 2 and 10mg of TET were dissolved in 10mL THF solution to prepare a solution containing 1mg / mL PTX 2 and 1mg / mL TET in THF (paclitaxel dimer-tetrandrine organic solution);

[0073] 1.2 Take out 1mL paclitaxel dimer-tetrandrine organic solution and add the carrier material mPEG-PLGA, the mass ratio of mPEG-PLGA, paclitaxel dimer and tetrandrine is 10:1:1; solution;

[0074] 1.3 Add the mixed solution dropwise to 10mL of vigorously stirred deionized water, control the solution dropping speed to 15s / drop, and continue stirring for 48h after the dropping to volatilize the THF solution;

[0075] 1.4 Stir at a speed of 500rpm for 48h;

[0076] 1.5 Rotate evaporation at 30°C for 20 minutes to remove non-volatile THF solution; then centrifuge at 5000rpm for 300s to remove uncoated PTX 2 and TET;

[...

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Abstract

The present application provides a self-assembled nano medicine-loaded micelle as well as a preparation method and application thereof, and belongs to the technical fields of pharmaceutical preparations, polymer materials and nano materials. The preparation provided by the invention is a co-delivery reduction-sensitive nanomicelle drug delivery system prepared from a paclitaxel dimer prodrug, tetrandrine and an amphiphilic copolymer material. The synthesized drug provided by the invention is coated in a polymer material to prepare the nanomicelle. According to the method, a disulfide bond is introduced in the synthesis of the dimer prodrug, the tetrandrine can be firstly released to inhibit multidrug resistance caused by excessive P-glycoprotein in tumor cells, and the paclitaxel dimer isreduced into paclitaxel in a reducing environment in the tumor cells to inhibit the proliferation and division of the tumor cells and achieve the purpose of reversing the multidrug resistance of the tumor cells; and at the same time, the micelle particles provided by the invention are uniformly distributed and in a monodispersion state, and can realize a passive targeting effect in vivo and significantly increase the accumulation of the drug in cells.

Description

technical field [0001] The application relates to the fields of pharmaceutical preparations, polymer materials and nanotechnology, in particular to a self-assembled nano drug-loaded micelle and its preparation method and application. Background technique [0002] Cancer is one of the diseases with the highest fatality rate in the world. Chemotherapy is the main method to treat cancer, but chemotherapy drugs usually cause systemic toxicity due to their poor biocompatibility. At present, drug delivery systems using nanocarrier materials to deliver anticancer drugs have been extensively studied, but there are still many defects, such as low drug loading, too large or too small micellar particle size, and so on. At the same time, chemotherapeutic drugs are likely to cause multidrug resistance of tumor cells and lead to chemotherapy failure. Multidrug resistance is mainly due to the excessive P-glycoprotein (P-gp) in tumor cells that can pump drugs out of the cell, thereby reduc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/34A61K47/55A61K31/337A61K31/4748A61P35/00A61K47/69A61K47/68
CPCA61K9/1075A61K31/337A61K31/4748A61K47/34A61K47/55A61K47/6853A61K47/6907A61P35/00A61K2300/00
Inventor 袁青梅秦溱宋亚东
Owner YUNNAN UNIV
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