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Composite nanoparticle as well as preparation method and application thereof

A nanoparticle, hydrolysis and condensation technology, applied in the direction of pharmaceutical formulations, drug combinations, medical preparations of non-active ingredients, etc., can solve the problems of drug delivery systems without reducing ATO, and achieve good acid-responsive drug release ability and strong immune activation effect, the effect of avoiding early leakage

Pending Publication Date: 2022-05-24
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] There are currently no studies on drug delivery systems that combine the tumor therapeutic effects of ATO and the immune activation effects of MSNs to reduce ATO toxicity and enhance drug efficacy

Method used

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  • Composite nanoparticle as well as preparation method and application thereof
  • Composite nanoparticle as well as preparation method and application thereof
  • Composite nanoparticle as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] Example 1 Aminated mesoporous silica nanoparticles (NH 2 -MSN) preparation

[0085] In this example, the effect of the dosage of silicon source TEOS and silane coupling agent APTES on aminated mesoporous silica nanoparticles (NH 2 -MSN) particle size, PDI and the effect of surface potential. Specific steps are as follows:

[0086] Preparation of CTAB solution: Weigh 0.1 g of CTAB powder and dissolve it in 48 mL of ultrapure water, heat and stir it in an oil bath at 50° C. to dissolve, to prepare a CTAB solution with a concentration of 0.055 mM.

[0087]When the temperature of 48 mL of 0.055 mM CTAB solution rose to 70 °C, the mixture of TEOS and APTES was rapidly added dropwise thereto, and the reaction was carried out at 80 °C for 2 h under stirring conditions. After the reaction, cooled, centrifuged to remove the supernatant, collected the bottom precipitate, and dispersed it in acidic ethanol ((EtOH:HCL)=100:1(v / v)) containing concentrated hydrochloric acid (37% b...

Embodiment 2

[0093] Example 2 Preparation of composite nanoparticles (PEG-MSN@ATO)

[0094] In this example, the aminated mesoporous silica nanoparticles (NH 2 -MSN) supported arsenic trioxide to obtain NH 2 -MSN@ATO followed by methoxypolyethylene glycol formaldehyde (mPEG-CHO) with NH 2 -MSN@ATO reaction to obtain composite nanoparticles (PEG-MSN@ATO); the aminated mesoporous silica nanoparticles (NH 2 -MSN) reacts with methoxy polyethylene glycol formaldehyde (mPEG-CHO) to obtain polyethylene glycol modified mesoporous silica nanoparticles (PEG-MSN), and the specific steps are as follows:

[0095] 1. Preparation of composite nanoparticles (PEG-MSN@ATO)

[0096] (1) Preparation of ATO solution: Weigh a certain amount of ATO powder and dissolve it in a NaOH solution with a pH value of 12. After the ATO is completely dissolved, adjust the pH to neutrality with concentrated hydrochloric acid, and then add ultrapure water to adjust the ATO solution to a certain value. volume so that the ...

Embodiment 3

[0107] Example 3 Detection of drug loading and encapsulation efficiency of composite nanoparticles (PEG-MSN@ATO)

[0108] In this example, the effects of different concentrations of ATO on drug loading and encapsulation efficiency were investigated, and the preparation method of PEG-MSN@ATO was the same as that in Example 2. It includes the following steps:

[0109] (1) Collection of supernatant: the supernatant A obtained in step (2) in Example 2 and the supernatant B obtained in (3) were combined and mixed, and the volume was precisely measured, and after the ultrapure water was diluted several times , take 10mL through a 0.22μm filter to obtain a filtrate.

[0110] (2) ICP-AES detection: get the filtrate of step (1) in the present embodiment of 5mL to detect the As concentration wherein with an inductively coupled plasma emission spectrometer, further convert into the content of free ATO wherein, calculate the encapsulation efficiency according to the formula ( Encapsulat...

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Abstract

The invention belongs to the technical field of pharmacy, and discloses a composite nanoparticle as well as a preparation method and application thereof. The nanoparticles comprise mesoporous silica, arsenic trioxide and polyethylene glycol, the arsenic trioxide is entrapped in the mesoporous silica, and the polyethylene glycol is modified on the surface of the mesoporous silica through an imine bond. Mesoporous silicon dioxide with a protein adsorption effect and an immune activation capability is used as a drug carrier to load arsenic trioxide, and hydrophilic polyethylene glycol is connected to the surface of the mesoporous silicon dioxide by using an acid-sensitive imine bond, so that the stability of the composite nanoparticle is enhanced; accurate release of arsenic trioxide at a tumor site and adsorption of mesoporous silica to tumor antigens are realized, so that activation of an immune system is realized, toxic and side effects of arsenic trioxide are reduced, and a treatment effect is enhanced.

Description

technical field [0001] The invention belongs to the technical field of pharmacy, and in particular relates to a composite nanoparticle and a preparation method and application thereof. Background technique [0002] Arsenic trioxide (ATO for short) is the main active ingredient of traditional Chinese medicine arsenic. In the 1970s, Chinese scholars first applied ATO to the treatment of acute promyelocytic leukemia and achieved remarkable results. With the in-depth study of ATO, it has been found that ATO has a good inhibitory effect on solid tumors such as liver cancer. Arsenic (As) atoms in ATO can significantly affect many intracellular signal transduction pathways and cause changes in cell functions, thereby inducing apoptosis, inhibiting angiogenesis and growth and promoting differentiation. Therefore, ATO is also used in the treatment of various malignant tumors. Research and Treatment. However, ATO is a highly toxic drug, and the amount of ATO required for the treatme...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/60A61K33/36A61P35/00A61P37/04
CPCA61K47/6923A61K47/60A61K33/36A61P35/00A61P37/04
Inventor 邱明丰王雪睿苏靖郑梦园
Owner SHANGHAI JIAO TONG UNIV
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