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Preparation method of multi-response targeting mesoporous silicon-based intelligent carrier

A kind of mesoporous silicon and intelligent technology, applied in the field of biomedicine, can solve the problems of insufficient curative effect, drug leakage and other problems, achieve the effect of optimal intelligent drug release behavior, improve curative effect and wide application prospect

Inactive Publication Date: 2019-01-18
嘉兴德扬生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, MSNs carriers that only respond to a single stimulus are often difficult to adapt to complex in vivo environments, resulting in insufficient efficacy or even early drug leakage.

Method used

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  • Preparation method of multi-response targeting mesoporous silicon-based intelligent carrier
  • Preparation method of multi-response targeting mesoporous silicon-based intelligent carrier
  • Preparation method of multi-response targeting mesoporous silicon-based intelligent carrier

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] A method for preparing a multi-response targeting mesoporous silicon-based smart carrier, the main steps are as follows:

[0021] (1) Weigh 0.5 g of cetyltrimethylammonium bromide and 0.24 g of sodium hydroxide into 240 mL of water, stir vigorously at 80 °C for half an hour, then add 0.5 mL of orthosilicate tetra Ethyl ester, then continue to react at 80 ° C for 2 h, centrifuge and wash the white precipitate with ethanol and water to obtain mesoporous silicon nanoparticles;

[0022] (2) Disperse 200 mg of the obtained mesoporous silicon nanoparticles in toluene, add 0.1 mL of silane coupling agent KH151 to it, reflux reaction at 70 °C overnight, and collect the surface-modified mesoporous silicon nanoparticles by high-speed centrifugation. porous silicon;

[0023] (3) Weigh 100 mg of mesoporous silicon with double bonds on the surface and disperse it in 40 ml of deionized water, add 12 mg of sodium lauryl sulfate, 67 mg of polyvinylcaprolactam, and 33 mg of double bond...

Embodiment 2

[0025] Take 20 mg of composite carrier and disperse it in 10 ml of phosphate buffer, add 1ml of doxorubicin aqueous solution (2mg / mL) to it, ultrasonically disperse and stir overnight in the dark, centrifuge to obtain the composite carrier loaded with doxorubicin, wash The obtained supernatant was collected and detected by an ultraviolet-visible spectrophotometer, and the calculated drug loading rate was 8.59%, and the encapsulation rate was 94%. The composite particles loaded with doxorubicin were dispersed in the buffer solution of pH 7.4 and pH 5.0 respectively, and 20 mM glutathione (GSH) was added to the buffer solution of each corresponding group, and heated at 37 and 42 °C The drug release experiment was carried out, and the cumulative released drug amount and the percentage of the total drug amount were plotted at each time point to obtain the cumulative release curve. From image 3 It can be seen from the buffer curve that when three stimuli are used to simultaneousl...

Embodiment 3

[0027] Human cervical cancer cells HeLa were planted in a 6-well plate at a density of 300,000 / well, and drug-loaded particle dispersions with doxorubicin concentrations of 0.5, 1, 2, 5, and 10 μg / ml were added to each well to mix with the cells. After co-cultivation for 4 h, the culture medium was discarded, washed with PBS, and trypsin was added to digest the cells, and the digested cell suspension was filtered for detection by flow cytometry. At the same time, HeLa cells were pretreated with pure hyaluronic acid culture medium with a concentration of 10 mg / ml, and co-cultured with drug-loaded particles, which were used as the control group for detection. The detection wavelength is Ex 479 nm / Em 587 nm. From Figure 4 It can be seen from the results that when the concentration of doxorubicin is constant, the cells pretreated with hyaluronic acid can significantly reduce the uptake of drug-loaded particles. Body shielding makes it unable to effectively bind specifically to ...

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Abstract

The invention relates to a preparation method of a multi-response targeting mesoporous silicon-based intelligent carrier. The preparation method of the intelligent carrier comprises the following steps: preparing mesoporous silicon nanoparticles, a silane coupling agent is used to modify it so as to form an active double bond on the surface, Disulfide bonded crosslinked gel shell was prepared on mesoporous silicon by emulsion polymerization in aqueous solution using potassium persulfate as initiator, bis (acryloyl) cystamine as crosslinking agent, polyvinylcaprolactam and methacryloylated hyaluronic acid as monomers. The composite carrier can simultaneously respond to three kinds of stimuli of temperature, high reducibility and enzyme, realize degradation of organic layer, open pore channel to release drug, synthesize zero leakage, multi-response and hyaluronic acid targeting, the intelligent carrier is expected to greatly improve the anti-tumor effect, and has good application prospect in the field of drug release.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to a method for preparing a multi-response targeting mesoporous silicon-based intelligent carrier. Background technique [0002] The effective treatment of cancer is of great significance for alleviating the suffering of patients, prolonging the survival time of patients and improving the quality of life of patients. However, traditional chemotherapeutic drugs have large toxic and side effects and do great damage to normal cells while killing tumor cells. Due to its unique advantages, the nano-controlled release system provides a new technical means for drug delivery and release in the field of nano-oncology. Stimuli-responsive mesoporous silicon nanoparticles have become one of the star materials in the field of nanomedicine, especially drug release, due to their unique "intelligence". With the continuous development of biomedical research, stimuli-responsive drug delivery systems can u...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/36A61K47/04A61K31/704A61P35/00
CPCA61K9/5115A61K9/5161A61K31/704A61P35/00
Inventor 陈良
Owner 嘉兴德扬生物科技有限公司
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