Preparation method and application of PH reversible controlled release meso-porous silicon nanometer drug delivery system

A technology of mesoporous silicon nanoparticles and nano-drug loading, applied in the fields of nano-biomedicine and tumor treatment, can solve the problem that pH-responsive controlled release behavior is not reversible, and achieve good biocompatibility and reduce toxicity.

Active Publication Date: 2020-10-20
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The first purpose of the present invention is to provide a pH-reversible controlled-release mesoporous silicon nano-drug-loading syste...

Method used

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  • Preparation method and application of PH reversible controlled release meso-porous silicon nanometer drug delivery system
  • Preparation method and application of PH reversible controlled release meso-porous silicon nanometer drug delivery system
  • Preparation method and application of PH reversible controlled release meso-porous silicon nanometer drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1. Preparation of a breast cancer-specific pH reversible controlled-release mesoporous silicon nano-drug delivery system (Figure 1).

[0045] (1) Synthesis of mesoporous silicon nanoparticles (MSNs): First, 500 mg of octadecyltrimethylammonium bromide (CTAB) was dispersed into 200 mL of ultrapure water and 40 mL of ethylene glycol solution as a template, and 2mol / L NaOH (1.75mL) was added to the above mixture. Then, after the mixture was continuously stirred at 80° C. for 1 h, 2.5 mL of tetraethylorthosilicate was added, and stirred at 80° C. for 2 h. Afterwards, in a high-speed refrigerated centrifuge, centrifuge at a speed of 12100 rpm for 20 min, and collect the solid precipitate. The precipitate was washed three times with ultrapure water and ethanol, and then dried in a vacuum oven. Finally, the dried samples were calcined in a muffle furnace at 550 °C for 6 h to remove the template agent CTAB, and the obtained dried samples were MSNs.

[0046] (2) Synth...

experiment example 2

[0050] Experimental example 2. Characterization of a breast cancer-specific pH reversible controlled-release mesoporous silicon nanometer drug delivery system.

[0051] Various nanocarriers prepared in Example 1 were used as detection objects for characterization to verify the success of each step of modification. Firstly, the changes of the surface of the mesoporous silicon nanoparticles before and after the modification of the polytannic acid layer were observed by a transmission electron microscope. figure 2 It shows that the mesoporous silicon nanoparticles are relatively regular circular and monodisperse, and at the same time, have a clearly visible mesoporous structure. After modifying the polytannic acid layer ( image 3 ), a layer of polymer film appeared on the surface of the particles, which reduced the dispersion and blurred the edges. At the same time, the mesoporous structure was no longer clear. This demonstrates the successful modification of the polytannic a...

experiment example 3

[0052] Experimental example 3. In vitro drug controlled release experiment of a breast cancer specific pH reversible controlled release mesoporous silicon nanometer drug loading system.

[0053] The DOX / MSNs-PTA-HER2 prepared in Example 1 was used as the detection object to carry out the in vitro controlled release experiment: a certain amount of the drug-loading system was dispersed in 10 mL of PBS solution, and transferred into a dialysis bag. Then, the dialysis bags are placed in buffers of different pH. At regular time intervals, 1 mL of buffer solution was taken out, and its absorbance was measured with a UV-Vis spectrophotometer, and the drug release was calculated by comparing with the standard curve. At the same time, add 1 mL of fresh buffer to the system to keep the total volume constant. First, the pH-controlled release performance of the nano-drug delivery system was studied in different and constant pH environments. Such as Figure 7 As shown, as the pH value g...

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Abstract

The invention provides a preparation method and application of a PH reversible controlled release meso-porous silicon nanometer drug delivery system. The PH reversible controlled release meso-porous silicon nanometer drug delivery system comprises meso-porous silicon nanoparticles and a compact polytannic acid layer, wherein the meso-porous silicon nanoparticles are loaded with drugs; and the compact polytannic acid layer is tightly wrapped on the surface of the meso-porous silicon nanoparticles so as to adjust and control specific release of the drugs at a tumour site. According to the preparation method and application of the PH reversible controlled release meso-porous silicon nanometer drug delivery system in the invention, the drugs are loaded by taking the meso-porous silicon nanoparticles as the carrier; tannic acid and a polyamine molecular cross-linking agent with amino at both ends perform spontaneous oxidation polymerization in an alkaline condition to form the polytannic acid layer, which is used as intelligent gating molecules wrapped on the surface of drug loaded meso-porous silicon; therefore, PH reversible responsive controlled release is realized; finally, by meansof Schiff base reaction or Michael addition reaction, a targeting agent with amino or sulfydryl is covalently crosslinked on the surface of the polytannic acid layer, so that specific targeted drug delivery on cancer cells is realized; the designed synthetic nanometer drug delivery system can effectively solve the problem that the traditional stimulus responsive drug delivery system is nearly irreversible; and thus, the secondary toxicity possibly due to the fact that a drug carrier has drug residues can be avoided.

Description

technical field [0001] The invention relates to the field of nano-biomedicine, in particular to a preparation method of a pH-reversible controlled-release mesoporous silicon nanometer drug-carrying system and its application in the field of tumor treatment. Background technique [0002] At present, cancer is still one of the greatest threats to human health, and at the same time, chemotherapy is still one of the most effective means of treating cancer. However, the serious defects of chemotherapy itself have greatly restricted its application, including: 1. The killing effect of chemotherapy drugs is often non-specific. While killing tumor cells, it can also kill normal tissue cells, causing huge toxicity. Side effects; 2. When chemotherapy drugs are transported in body fluids, the leakage of drugs is serious, and the amount of drugs that finally reach the tumor site is often low; 3. Cancer cells have poor absorption capacity of chemotherapy drugs, etc. [0003] With the de...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/34A61K47/04A61K47/26A61K47/42A61K31/704A61P35/00
CPCA61K9/5169A61K9/5123A61K9/5115A61K9/5146A61K31/704A61P35/00
Inventor 陈超马同昊王平汤文
Owner EAST CHINA UNIV OF SCI & TECH
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