Preparation method of pH-responsive adriamycin nano-drug capsule with surface positive charge

A nano-drug, doxorubicin technology, applied in the direction of drug combination, microcapsule, capsule delivery, etc., can solve the problems of degradation cycle and degradation efficiency, low drug loading, tissue toxicity and side damage, etc., and achieves a small average particle size. , The effect of fast dissolution rate and large dissolution rate

Active Publication Date: 2017-05-31
BEIJING UNIV OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The most widely studied and used drug carrier is polymer micelles / vesicles (amphiphilic copolymers, liposomes), but it has low drug loading, poor stability, and poor encapsulation efficiency, and it is very easy to circulate in the body During the process, the anti-tumor agent will leak out before it reaches the tumor site, causing serious toxic and side effects to normal tissues.
Although colloidal particles of biodegradable polymers (polylactic acid, lactic acid-glycolic acid copolymer, polycaprolactone, etc.) have high drug loading and encapsulation efficiency, due to the degradation cycle and degradation efficiency of the polymer, Inhibited drug release efficiency
On the other hand, because most polymer nano drug carriers do not have the "proton sponge effect", the escape efficiency of endosomes and lysosomes in the process of loading into cells is low, and it is difficult to effectively deliver drugs to the cell matrix and nuclei

Method used

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  • Preparation method of pH-responsive adriamycin nano-drug capsule with surface positive charge
  • Preparation method of pH-responsive adriamycin nano-drug capsule with surface positive charge
  • Preparation method of pH-responsive adriamycin nano-drug capsule with surface positive charge

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Add 0.1 mol of OP-10, 0.12 mol of triethylamine and 80 mL of tetrahydrofuran into the three-necked flask, place the three-necked flask in ice water, and stir with an electromagnetic stirrer. Dissolve 0.12 mol of AC in tetrahydrofuran, and then add it dropwise into a three-neck flask. After the addition is complete, react for 5 hours, and keep the temperature at 0-5°C. The tetrahydrofuran was removed from the reaction product by a rotary evaporator, and the temperature was set at 50 °C. Then add 200 mL of acetone, separate to obtain the supernatant containing OP-AC, then use a rotary evaporator (set temperature at 40° C.) to remove the acetone, and centrifuge to obtain OP-AC. Dry in a vacuum oven to obtain OP-AC.

[0046] From figure 1 It can be seen from the NMR diagram shown that there is an obvious characteristic peak around 3.5 ppm, indicating that there is a double bond in the experimentally synthesized OP-AC.

[0047] From figure 2 It can be seen from the infr...

Embodiment 2

[0049]Weigh 5 mg of doxorubicin hydrochloride, dissolve it in 1 mL of dimethyl sulfoxide at room temperature, add 4 μL of triethylamine to remove hydrochloric acid according to the molar ratio of triethylamine: doxorubicin hydrochloride is 3:1, react for 10 min, record For the mixture ①. Dissolve 1 mg of OP-AC in 25 mL of deionized water, stir for 10 min, and record it as the mixture ②. Add the mixed solution ① to the mixed solution ②, react for 20 minutes, and record it as the mixed solution ③. According to the ratio of doxorubicin / (AM+GDM) as 1 / 0.03 (mass ratio), and the mass ratio of AM and GDM as 1 / 0.4, add AM to the mixture ③, add GDM after 10 minutes, and then add 0.2 mg ammonium persulfate, add TEMED according to the mass ratio of monomer and TEMED as 1 / 5, react for 1.5h, and record it as the mixed solution ④. Put the mixed solution ④ into a dialysis bag (MW=3500), dialyze with deionized water, store in the dark at 4°C, change the deionized water every 4 hours, and re...

Embodiment 3

[0052] Weigh 5 mg of doxorubicin hydrochloride, dissolve it in 1 mL of dimethyl sulfoxide at room temperature, add 4 μL of triethylamine to remove hydrochloric acid according to the molar ratio of triethylamine: doxorubicin hydrochloride is 3:1, react for 10 min, record For the mixture ①. Dissolve 1 mg of OP-AC in 25 mL of deionized water, stir for 10 min, and record it as the mixture ②. Add the mixed solution ① to the mixed solution ②, react for 20 minutes, and record it as the mixed solution ③. According to the ratio of doxorubicin / (AM+GDM) as 1 / 0.05 (mass ratio), and the mass ratio of AM and GDM as 1 / 0.4, add AM to the mixture ③, add GDM after 10 minutes, and then add 0.2 mg ammonium persulfate, add TEMED according to the mass ratio of monomer and TEMED as 1 / 5, react for 1.5h, and record it as the mixed solution ④. Put the mixed solution ④ into a dialysis bag (MW=3500), dialyze with deionized water, store in the dark at 4°C, change the deionized water every 4 hours, and r...

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Abstract

The invention relates to a preparation method of a pH-responsive adriamycin nano-drug capsule with a surface positive charge. The preparation method comprises the steps of uniformly mixing adriamycin nano-drug particles with surfaces modified by acrylate with a certain amount of neutral monomer acrylamide (AM), a positively charged monomer N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) and a pH-responsive degrading cross-linking agent in deionized water, adding an oxidation-reduction initiator ammonium persulfate / tetramethylethylenediamine (TEMED) to initiate in-situ free radical polymerization, and carrying out dialysis and freeze drying, so as to obtain the adriamycin nano-drug capsule. By changing the type of cross-linking agents and regulating the dosages of the monomers and cross-linking agents, the adriamycin nano-drug capsule with relatively good properties such as relatively small mean grain size, dispersion uniformity, relatively high dissolution velocity and dissolution rate can be obtained. The invention provides a novel thought and option, the operation of the method is simple, and the accurate control of the structure and the surface and the in-vivo efficient delivery of the adriamycin nano-drug capsule can be realized.

Description

technical field [0001] The invention belongs to the field of medicine preparation, and in particular relates to a preparation method of pH-responsive doxorubicin nano drug capsules with positive surface charges. Background technique [0002] According to the data released by the Ministry of Health of China, in 2015, about 4.3 million people in China were diagnosed with cancer, and another 2.8 million died of cancer. Cancer has become the most important disease that endangers human health. One of the main treatments for cancer is drug therapy. However, most of the current anticancer drugs have poor water solubility, poor stability, low selectivity to tumor tissue, and poor curative effect. Strong toxicity and other defects. Therefore, finding a reliable drug carrier is the key to solving these problems. [0003] The most widely studied and used drug carrier is polymer micelles / vesicles (amphiphilic copolymers, liposomes), but it has low drug loading, poor stability, and poo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F290/06C08F220/56C08F222/20C08F222/38C08F4/40A61K47/58A61K47/69A61K9/51A61K31/704A61P35/00
CPCA61K9/5138A61K31/704C08F4/40C08F290/062C08F222/103
Inventor 张建军宋晓庆王洁欣乐园陈建峰
Owner BEIJING UNIV OF CHEM TECH
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