Arsenic-trioxide-carrying pH-responsive mesoporous silica nanoparticle and preparation method thereof

A technology of mesoporous silica and arsenic trioxide, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of lack of specificity in ATO distribution, limited application, adverse reactions, etc.

Active Publication Date: 2015-05-27
ZHEJIANG CHINESE MEDICAL UNIVERSITY
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  • Abstract
  • Description
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  • Application Information

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Problems solved by technology

Some scholars have found that ATO can also inhibit the growth and induce apoptosis of a variety of solid tumor cells, but due to the lack of specificity in the distribution of ATO in the body, when it reaches an effective concentration, it will often cause serious adverse reactions to other normal tissues; in addition, ATO Short half-life and rapid elimination after administration, thus limiting its use in solid tumors

Method used

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  • Arsenic-trioxide-carrying pH-responsive mesoporous silica nanoparticle and preparation method thereof
  • Arsenic-trioxide-carrying pH-responsive mesoporous silica nanoparticle and preparation method thereof
  • Arsenic-trioxide-carrying pH-responsive mesoporous silica nanoparticle and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Embodiment 1: the preparation of nanoparticle

[0026] NH 2- Preparation of MSNs: One-step preparation of aminated mesoporous silica by co-precipitation method. 0.3g CTAB was dissolved in ultrapure water, and an appropriate amount of 2mol / L NaOH solution was added to adjust the pH to about 11.5. After magnetic stirring at 80°C for 0.5 h, the mixed solution containing 1 mL of TEOS and 0.5 mL of APTES was added dropwise to the CTAB solution, reacted for 2 h, left to mature for 6 h, centrifuged at 20 000 r / min for 30 min, acidic ethanol (absolute ethanol and Hydrochloric acid (volume ratio 10:1) was washed three times to remove the template agent CTAB. Wash three times with ultrapure water, centrifuge, and freeze-dry to obtain NH 2 -MSNs.

[0027] Preparation of PAA-ATO-MSNs: Accurately weigh 40 mg of MSNs freeze-dried powder, add to 10 mL of 1 mg / mL ATO solution, and stir for 24 hours. 20 000r / min high-speed centrifugation for 30 minutes to remove free ATO, washed th...

Embodiment 2

[0038] Example 2: Determination of Encapsulation Efficiency and Drug Loading Capacity

[0039] Instrument working conditions

[0040] RF power: 1150W; plasma flow: 50L / min; auxiliary gas flow: 0.5L / min; atomizer flow: 0.3L / min; pump speed: 50r / min; instrument stabilization delay: 5s; cleaning time: 30s ; Carrier gas: argon (purity 99.99%); analytical line: 189nm.

[0041] Linear relationship investigation

[0042] Precisely pipette an appropriate amount of arsenic standard solution into a 100mL volumetric flask, dilute to the mark with dilute nitric acid, and obtain a series of arsenic standard solutions with mass fractions of 0, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 mg / L. Measure the emission intensity of each element in the standard blank solution and each standard solution at 189nm, take the emission intensity (Y) as the ordinate, and the concentration (C) as the abscissa, draw a standard curve and get the correlation coefficient by the software iTAVA: Y= 1847.2C+19.606 (r=0.999...

Embodiment 3

[0048] Implementation 3: In vitro drug release study

[0049] PBS (5.0, 6.0, 7.4) solutions with different pH were selected as the release medium to investigate the release characteristics of ATO in the drug-loaded nanoparticles. ATO 0.5mg) was dissolved or dispersed with 2mL release medium, placed in a pre-treated dialysis bag, sealed after removing air bubbles, placed in 100mL release medium, and shaken in a constant temperature water bath (75r / min) at (37±0.5)°C, Accurately sample 2 mL at 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours, and immediately add an equal amount of fresh release medium at the same temperature and pH, and the samples are filtered through a 0.22 μm microporous filter. Membrane filtration, measure the drug content in the release medium after taking the continued filtrate dilution, calculate the cumulative drug release rate (Q%), and draw the drug release curve as Figure 9 . It can be seen from the figure that there is no significant dif...

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Abstract

The invention discloses an arsenic-trioxide-carrying pH-responsive mesoporous silica nanoparticle and a preparation method thereof. The preparation method of the arsenic-trioxide-carrying pH-responsive mesoporous silica nanoparticle mainly comprises the following steps: preparing amino modified mesoporous silica by adopting a coprecipitation method, and loading conjugate acid and base ATO and PAA through electrostatic adsorption for preparing PAA-ATO-MSNs. The prepared PAA-ATO-MSNs are circular or quasi-circular in appearance under a transmission electron microscope, average particle size is (158.6+ / -1.32)nm, Zeta potential is (-28.40+ / -0.34)mV, and encapsulation efficiency and drug loading rate are (40.95+ / -3.21)% and (11.42+ / -1.75)% respectively; in vitro drug release is pH-responsive, and accumulated release amount is increased along with reduction of pH value; pharmacokinetic study shows that compared with ATO-Sol and ATO-MSNs, t1 / 2beta of PAA-ATO-MSNs is obviously prolonged and AUC is obviously increased (P is less than 0.01); and PAA-ATO-MSNs in vitro drug release has obvious pH responsiveness and sustained release property, in vivo pharmacokinetic behaviours of a rat can be obviously improved, and the arsenic-trioxide-carrying pH-responsive mesoporous silica nanoparticle carrier can serve as an ATO tumour-targeted drug delivery system and has a good application prospect.

Description

technical field [0001] The invention relates to a method for preparing polyacrylic acid (PAA) modified amino-modified mesoporous silica (MSNs) loaded arsenic trioxide (ATO) nanoparticles (PAA-ATO-MSNs) and a preparation method thereof. Background technique [0002] Arsenic trioxide (ATO) is the effective active ingredient of the traditional Chinese medicine arsenic, and it is mainly used clinically for the treatment of acute promyelocytic leukemia. Some scholars have found that ATO can also inhibit the growth and induce apoptosis of a variety of solid tumor cells, but due to the lack of specificity in the distribution of ATO in the body, when it reaches an effective concentration, it will often cause serious adverse reactions to other normal tissues; in addition, ATO The short half-life and rapid elimination after administration limit its application in solid tumors. [0003] Mesoporous silica nanoparticles (MSNs) are a new type of inorganic mesoporous materials with large ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K33/36A61K47/04A61K47/32A61P35/02A61P35/00
Inventor 李范珠郭曼曼李晶晶诸佳珍王国伟管佳妮徐骏军刘洋洋费伟东
Owner ZHEJIANG CHINESE MEDICAL UNIVERSITY
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