Folic acid mediated dual-drug-loading targeting polymeric micelle and preparation method and application thereof

A technology of polymer glue and double drug loading, which can be used in drug combinations, pharmaceutical formulations, medical preparations with non-active ingredients, etc. Effect

Inactive Publication Date: 2019-08-16
NANJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Purpose of the invention: In order to solve the above-mentioned technical problems, the present invention provides a folic acid-mediated targeted dual drug-loaded polymer micelle and its preparation method and application. The polymer micelle can solve the problem of poor water solubility of paclitaxel, and can Targeting folic acid to improve anti-cancer effect

Method used

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  • Folic acid mediated dual-drug-loading targeting polymeric micelle and preparation method and application thereof
  • Folic acid mediated dual-drug-loading targeting polymeric micelle and preparation method and application thereof
  • Folic acid mediated dual-drug-loading targeting polymeric micelle and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] 1) Preparation of polylysine polymer macromolecule (PLL):

[0047]

[0048] Step 1: Dissolve Lys(Z) (5g, 17.85mmol) in 65ml of anhydrous tetrahydrofuran, stir for 30min, add phosgene (2.12g, 7.15mmol), and react for 3 hours at 50°C under nitrogen . A large amount of pre-cooled n-hexane was added and stirred for 10 min, and the compound Lys(Z)-NCA was obtained by suction filtration. 1H NMR (400MHz, DMSO-d 6 ):δ9.11(1H,α-NH),7.34(5H,Ph),5.00(2H,-CH 2 Ph), 4.42(1H,-CH), 2.98(2H,-CH2), 1.69(2H,-CH2), 1.4(2H,-CH2), 1.28(2H,-CH2).FT-IR(cm -1 ): 943 (O=C-O-C=O stretching vibration absorption band NCA), 1688 (C=O in the Cbz group), 1774, 1812 (C=O in the NCA), 1250 (C-O in the Cbz group).

[0049] Step 2: The compound Lys(Z)-NCA (5.10g, 16.65mmol) obtained in the previous step was dissolved in 25mL DMF under the action of nitrogen, and then hexylamine (55.65μg, 0.55mmol) dissolved in 1ml DMF was added to the reaction , Heat to 35°C for 3 days. A large amount of pre-cooled methyl ...

Embodiment 2

[0072] (1) Determination of sample solid content:

[0073] Weigh the glass bottle 5 times and calculate the average value. Take 1 mL sample (such as PGA-PTX) into the glass bottle and dry it to constant weight in a vacuum drying oven. Then weigh the bottle 5 times and calculate the average value to obtain the solid content of the sample.

[0074] (2) Drawing of standard curve:

[0075] Different concentrations of FA, PTX and GEM solutions were prepared with methanol, and the absorbance was measured with an ultraviolet spectrophotometer. The detection wavelength of folic acid is 283nm, the detection wavelength of paclitaxel is 230nm, and the detection wavelength of gemcitabine is 269nm. The standard curve is drawn according to the UV absorbance corresponding to each concentration, such as Figure 5 Shown. Calculate the concentration of the drug in the sample according to the standard curve.

[0076] (3) Formula for calculating drug loading and grafting rate:

[0077] Drug loading = dr...

Embodiment 3

[0081] Example 3: Performance test of the folate-mediated targeted dual drug-loaded polymer micelles of the present invention

[0082] (1) Preparation of nano-FA-PMDNPs containing folic acid:

[0083] The preferred mass ratio is 20:1: Take PGA-PTX, PGA-GEM, and PGA-FA with a pipette, and add 50 μL of PLL aqueous solution to obtain a clear and transparent solution. Through the mutual attraction of positive and negative charges, they self-assemble into nanoparticles by standing overnight.

[0084] (2) Preparation of PTX-GEM NPs without folic acid nanoparticles:

[0085] The preferred mass ratio is 20:1: Use a pipette to take 300 μL of each of PGA-PTX and PGA-GEM, and add 400 μL of PLL aqueous solution to obtain 1 mL of a clear and transparent solution. Through the mutual attraction of positive and negative charges, they self-assemble into nanoparticles by standing overnight.

[0086] (3) The stability of FA-PMDNPs and PMDNPs

[0087] The nanoparticles (0.5 mg / mL) were kept at room temper...

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Abstract

The invention discloses a folic acid mediated dual-drug-loading targeting polymeric micelle and a preparation method and application thereof. The polymeric micelle is a nanoparticle formed by that polyglutamic acid grafted with paclitaxel, gemcitabine and folic acid is subjected to electrostatic self-assembly with polylysine. Compared with the prior art, the dual-drug-loading targeting polymeric micelle has advantages that by joint use of paclitaxel and gemcitabine, great antitumor effects can be achieved, the problem of poor water solubility of paclitaxel is solved, efficacy improvement and toxicity reduction are realized by targeting, and probability is provided for cancer targeted low-toxicity treatment.

Description

Technical field [0001] The invention relates to a folic acid-mediated targeting dual drug-loaded polymer micelle, a preparation method and application thereof, and belongs to the technical field of drug-loaded polymer micelles. Background technique [0002] Nanomedicine, as an emerging technology, provides an important R&D platform for precise positioning and early diagnosis, targeting, long-term and combined therapy of tumors, to overcome the bottleneck problem of non-specific targeting and non-selective damage to body tissues by traditional drugs Provides the possibility. In recent years, a large number of researchers have designed and synthesized a large number of nano drugs that can be used for tumor diagnosis and treatment based on polymer micelles, dendrimers, quantum dots, nano gold, nano mesoporous silicon and other nano drug carriers, mainly through the "core-shell" structure Design, surface modification and other methods to improve the properties of nanomedicine. Comp...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K31/337A61K31/7068A61K47/64A61P35/00C08G69/10C08G69/48
CPCA61K9/1075A61K31/337A61K31/7068A61K47/645A61P35/00C08G69/10C08G69/48A61K2300/00
Inventor 沈健朱永强王雪源肖翰詹诗雨
Owner NANJING NORMAL UNIVERSITY
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