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Application and preparation method of metastatic encephaloma targeted nano drug delivery system with effects of LRP1 up-regulation and targeting

A technology of brain metastases and drug delivery system, applied in the field of nanobiomedicine

Inactive Publication Date: 2019-06-21
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, recent reports indicate that even a highly effective target like Angiopep-2 mediates only 0.2-0.3% of the injected dose into the brain

Method used

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  • Application and preparation method of metastatic encephaloma targeted nano drug delivery system with effects of LRP1 up-regulation and targeting
  • Application and preparation method of metastatic encephaloma targeted nano drug delivery system with effects of LRP1 up-regulation and targeting
  • Application and preparation method of metastatic encephaloma targeted nano drug delivery system with effects of LRP1 up-regulation and targeting

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Experimental program
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preparation example Construction

[0067] A preparation method of a brain metastases-targeted nano drug delivery system that can upregulate and target LRP1, comprising:

[0068] Step 1: Dissolve the biodegradable polymer base carrier in an appropriate amount of organic solvent, and add a certain amount of functional small molecules that can up-regulate LRP1 to form an oil phase;

[0069] In one embodiment, this step can be specifically performed as follows: the biodegradable polymer base carrier is dissolved in an appropriate amount of organic solvent, and a certain amount of functional small molecules that can up-regulate LRP1 is added to form an oil phase, wherein the The polymer materials mentioned are polylactic acid (molecular weight of 0.3-15,000, 15-30,000, 3-55,000, 55-90,000), polylactic acid-glycolic acid (molecular weight of 0.1-15,000, 15-24,000, 2.4-3.8 million, 3.8-5.3 million, 5.3-70,000, 7-88,000, the ratio of lactide and glycolide is 75 / 50 or 50 / 50), polycaprolactone (molecular weight is 0.4-40...

Embodiment 1

[0095] Weigh 50 mg of polylactic acid-glycolic acid-polylysine and 50 mg of simvastatin and dissolve them in 1 mL of ethyl acetate as the oil phase. Weigh 25 mg of doxorubicin hydrochloride and dissolve in 100 μL of water. As the inner water phase, the solution was added dropwise to the oil phase under vortexing conditions to form a water-in-oil emulsion; then the emulsion was added dropwise to 4 mL of 2.5% polyvinyl alcohol solution under vortexing conditions, and phacoemulsification was performed A water-in-oil-in-water emulsion is formed; the emulsion is quickly poured into 50 mL of a 0.3% polyvinyl alcohol solution, and the ethyl acetate is removed by stirring and volatilization; the obtained nanoparticle suspension is centrifuged at a low speed of 1000 rpm for 5 min to obtain a supernatant to remove larger nanoparticles particles and unencapsulated simvastatin; the aforementioned supernatant was subjected to ultracentrifugation at 30,000 rpm for 20 min to obtain nanopartic...

Embodiment 2

[0097] Weigh 50 mg of polylactic acid-glycolic acid-polylysine and 50 mg of simvastatin and dissolve them in 1 mL of ethyl acetate as the oil phase. Weigh 25 mg of doxorubicin hydrochloride and dissolve in 100 μL of water. As the inner water phase, the solution was added dropwise to the oil phase under vortexing conditions to form a water-in-oil emulsion; then the emulsion was added dropwise to 4 mL of 2.5% polyvinyl alcohol solution under vortexing conditions, and phacoemulsification was performed A water-in-oil-in-water emulsion is formed; the emulsion is quickly poured into 50 mL of a 0.3% polyvinyl alcohol solution, and the ethyl acetate is removed by stirring and volatilization; the obtained nanoparticle suspension is centrifuged at a low speed of 1000 rpm for 5 min to obtain a supernatant to remove larger nanoparticles particles and unencapsulated simvastatin; the aforementioned supernatant was subjected to ultracentrifugation at 30,000 rpm for 20 min to obtain nanopartic...

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Abstract

The invention discloses an application and preparation method of a metastatic encephaloma targeted nano drug delivery system with effects of LRP1 up-regulation and targeting. By a biologically-degradable high polymer material serving as a basic carrier, internally-loaded functional small molecules capable of up-regulating low-density lipoprotein receptor related protein 1 (LRP1), and an LRP1 targeting ligand for surface modification, the nano drug delivery system is capable of realizing targeted delivery of the internally-loaded LRP1 up-regulation molecules under the action of the surface ligand so as to specifically up-regulate the surface LRP1 level of cerebral microvascular endothelial cells and metastatic encephaloma cells, accumulation of the LRP1 targeting ligand modified nano drug delivery system in metastatic encephaloma is promoted, and accordingly the nano drug delivery system forms a self-promoted drug delivery system. The nano drug delivery system which loads antitumor drugs realizes delivery of drugs in therapeutic concentration, and the preparation method is simple and high in operability and economic benefit.

Description

technical field [0001] The invention belongs to the technical field of nanometer biomedicine, and in particular relates to a preparation method and application of a brain metastases targeted nanometer drug delivery system that can upregulate and target LRP1. Background technique [0002] Brain metastases are a disease in which malignant tumors from other parts of the body metastasize to the brain. About 24-45% of cancer patients develop brain metastases, and it has become a common clinical problem in oncology. With the advancement of diagnostic technology and the prolongation of survival of patients with tumors of surrounding tissues, the incidence of brain metastases continues to increase. At present, the main treatment for brain metastases is surgery, combined with radiotherapy and chemotherapy; however, these methods have a series of drawbacks, including difficult surgery, difficult to remove effectively and completely, and the side effects of whole brain radiotherapy, wh...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K47/34A61K47/22A61K45/00A61P35/04
Inventor 韩亮郭倩
Owner SUZHOU UNIV
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