Nano particle capable of promoting tumor clotting and enzyme/pH dual responsive drug release and preparation method and application thereof

A nanoparticle, responsive technology, applied in the field of biomedical materials and drug controlled release

Active Publication Date: 2019-10-08
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, how to induce blood coagulation in tumor blood vessels to quickly kill cancer cells through more accurate, effective and convenient ideas and methods still needs research and breakthroughs

Method used

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  • Nano particle capable of promoting tumor clotting and enzyme/pH dual responsive drug release and preparation method and application thereof
  • Nano particle capable of promoting tumor clotting and enzyme/pH dual responsive drug release and preparation method and application thereof
  • Nano particle capable of promoting tumor clotting and enzyme/pH dual responsive drug release and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] (1) Preparation of core layer calcium carbonate drug-loaded nanoparticles

[0092]① Dissolve 2.046g of surfactant dodecyl ammonium bromide (CTAB) in 5mL of co-surfactant n-butanol and 27mL of oil phase n-hexane, stir at a constant temperature of 40°C for 0.5h, and form an oil phase after complete dissolution. Then add 0.1mL of 2mol / L calcium chloride aqueous solution and 0.1mL of 2mol / L sodium carbonate aqueous solution to the oil phase (volume ratio of oil phase and water phase is 160:1), stir and react for 12h, centrifuge with n-hexane After washing with alkane and ethanol three times, calcium carbonate nanoparticles were obtained after drying. The X-ray diffractometer pattern of calcium carbonate nanoparticles is as follows figure 2 As shown, it can be proved that the prepared calcium carbonate belongs to the calcite type. Transmission electron microscopy of calcium carbonate nanoparticles as image 3 As shown in the figure, the results show that the spherical sh...

Embodiment 2

[0107] (1) Preparation of core layer calcium carbonate drug-loaded nanoparticles

[0108] ① Dissolve 2.046g of surfactant dodecyl ammonium bromide (CTAB) in 5mL of co-surfactant n-butanol and 27mL of oil phase n-hexane, stir at a constant temperature of 40°C for 0.5h, and form an oil phase after complete dissolution. Then add 0.5mL of 2mol / L calcium chloride aqueous solution and 0.5mL of 2mol / L sodium carbonate aqueous solution (the volume ratio of oil phase and water phase is 32:1) to the oil phase, stir and react for 12h, and use n-hexane after centrifugation. After washing with alkane and ethanol three times, calcium carbonate nanoparticles were obtained after drying. The TEM results of the calcium carbonate nanoparticles showed spherical shape with an average particle size of 300 nm and a potential of +8 mV.

[0109] ② Take 6 mg of calcium carbonate nanoparticles prepared in step ① and disperse it in 2 mL of deionized water, take 4 mg of topotecan hydrochloride (TPT) and ...

Embodiment 3

[0118] (1) Preparation of core layer calcium carbonate drug-loaded nanoparticles

[0119] ① Dissolve 2.046g of surfactant dodecyl ammonium bromide (CTAB) in 5mL of co-surfactant n-butanol and 27mL of oil phase n-hexane, stir at a constant temperature of 40°C for 0.5h, and form an oil phase after complete dissolution. Then add 0.05mL of 2mol / L calcium chloride aqueous solution and 0.05mL of 2mol / L sodium carbonate aqueous solution (the volume ratio of oil phase to water phase is 320:1) respectively into the oil phase, and stir for 12h. After washing with alkane and ethanol three times, calcium carbonate nanoparticles were obtained after drying. The transmission electron microscope results of calcium carbonate nanoparticles showed spherical shape with an average particle size of 50 nm and a potential of +5 mV.

[0120] ② Take 2 mg of calcium carbonate nanoparticles prepared in step ① and disperse them in 2 mL of deionized water, take 4 mg of paclitaxel (PTX) and dissolve it in ...

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Abstract

The invention belongs to the field of biomedical materials and drugs control and release and clotting properties, and specifically relates to a nano particle capable of promoting tumor clotting and enzyme / pH dual responsive drug release and a preparation method and application thereof. The nano particle is provided with a nuclear shell structure, a nuclear layer is a calcium carbonate nano particle loaded with drugs, and a shell layer is a cross-linked structure formed by hyaluronic acid molecules modified by polyethylene glycol and methylacrylic acid anhydride through ultraviolet illumination. Electronegativity, hydrophilicity and the cross-linked structure of the shell layer can improve blood stability of the nano particle, specific binding of hyaluronic acids and cancer cell CD-44 receptors achieves active targeting, a nano drug carrier rapidly releases Ca<2+> in the tumor acidic environment and migrates to a tumor blood vessel and induces clotting, sugar supply to the cancer cellsis blocked, at the same time, the drugs are released rapidly under dual stimulation response of hyaluronidase / pH, the purpose of synergistic killing of the cancer cells is achieved, and the nano particle is of great significance for cancer treatment.

Description

technical field [0001] The invention belongs to the field of controlled release of biomedical materials and drugs, and in particular relates to a nanoparticle capable of promoting tumor coagulation and dual enzyme / pH responsive drug release, and a preparation method and application thereof. Background technique [0002] Malignant tumors have seriously threatened human life and health. In the early stage, surgical resection is often used, while in the late stage, most of them rely on chemotherapy, radiotherapy, and immunotherapy. However, when killing cancer cells, it also kills normal tissue cells, with serious side effects. The "starve tumor" therapy proposed in recent years provides a new idea for cancer treatment. The team of Hu Xun of the Second Zhejiang Medical Hospital used the "starvation tumor" therapy, combined with arterial intubation chemoembolization and injection of sodium bicarbonate, to block tumor blood vessels, block the sugar supply of cancer cells, and rem...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/60A61K45/00A61P35/00A61K31/704A61K31/4745A61K31/337
CPCA61K47/6939A61K47/60A61K45/00A61P35/00A61K31/704A61K31/4745A61K31/337
Inventor 赵剑豪李慧茹容建华
Owner JINAN UNIVERSITY
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