Doxorubicin and TRAIL co-supported albumin nanoparticle targeting preparation and preparation method thereof

An albumin nanoparticle, doxorubicin-loaded technology, applied in peptide/protein components, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc., can solve cell apoptosis, prone to drug resistance, etc. problem, to achieve the effect of reducing toxic side effects and increasing accumulation

Inactive Publication Date: 2015-11-04
SHENYANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

TRAIL is prone to drug resistance when used alone, and synergistic or additive effects can be seen in combination with chemotherapy drugs (such as etoposide, cisplatin, doxorubicin and 5-fluorouracil), which can lead to apoptosis

Method used

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  • Doxorubicin and TRAIL co-supported albumin nanoparticle targeting preparation and preparation method thereof
  • Doxorubicin and TRAIL co-supported albumin nanoparticle targeting preparation and preparation method thereof
  • Doxorubicin and TRAIL co-supported albumin nanoparticle targeting preparation and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Preparation of albumin nanoparticle-targeted formulations co-loaded with doxorubicin and TRAIL

[0039] (1) Take BSA to make a 2% (g / ml) aqueous solution, and adjust the pH to 8.0 with 1 mole per liter of sodium hydroxide solution. Take 1 ml of BSA solution, add 4 ml of 0.02% doxorubicin hydrochloride ethanol solution dropwise to it with stirring, at a rate of 10 ml / min, to obtain a drug-containing albumin solution. Then, add 4% glutaraldehyde ethanol solution dropwise to the drug-containing albumin solution under stirring, continue to stir for 2 hours, then transfer to a rotary evaporator, and rotary evaporate at 40°C for 20 minutes under vacuum to remove ethanol. The obtained product was centrifuged at 10°C and 14,000 rpm for 10 minutes, discarded the centrifuged supernatant, washed and centrifuged twice with distilled water repeatedly, and discarded the supernatant to obtain nanoparticles. Then add distilled water to the nanoparticles and vortex to dispers...

Embodiment 2

[0043] Example 2 Preparation of albumin nanoparticle-targeted formulations co-loaded with doxorubicin and TRAIL

[0044] (1) Take BSA to make a 1% (g / ml) aqueous solution, and adjust the pH to 8.0 with 1 mole per liter of sodium hydroxide solution. Take 1 ml of BSA solution, add 4 ml of 0.01% ethanol solution of doxorubicin dropwise to it under stirring, at a speed of 10 ml / min, to obtain a drug-containing albumin solution. Then, add 4% glutaraldehyde ethanol solution dropwise to the drug-containing albumin solution under stirring, continue to stir for 2 hours, then transfer to a rotary evaporator, and rotary evaporate at 40°C for 20 minutes under vacuum to remove ethanol. The obtained product was centrifuged at 10°C and 14,000 rpm for 10 minutes, discarded the centrifuged supernatant, washed and centrifuged twice with distilled water repeatedly, and discarded the supernatant to obtain nanoparticles. Then add distilled water to the nanoparticles and vortex to disperse...

Embodiment 3

[0047] Example 3 Preparation of Drug-loaded Albumin Nanoparticles Targeting Folate Receptor and Tumor pH-Sensitive Release

[0048] (1) Take BSA to make a 5% (g / ml) aqueous solution, and adjust the pH to 8.0 with 1 mole per liter of sodium hydroxide solution. Take 1 ml of BSA solution, add 4 ml of 0.05% ethanol solution of doxorubicin dropwise to it under stirring, at a speed of 10 ml / min, to obtain a drug-containing albumin solution. Then, add 4% glutaraldehyde ethanol solution dropwise to the drug-containing albumin solution under stirring, continue to stir for 2 hours, then transfer to a rotary evaporator, and rotary evaporate at 40°C for 20 minutes under vacuum to remove ethanol. The obtained product was centrifuged at 10°C and 14,000 rpm for 10 minutes, discarded the centrifuged supernatant, washed and centrifuged twice with distilled water repeatedly, and discarded the supernatant to obtain nanoparticles. Then add distilled water to the nanoparticles and vortex ...

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Abstract

A doxorubicin and TRAIL co-supported albumin nanoparticle targeting preparation and a preparation method thereof. The preparation consists of doxorubicin hydrochloride DOX.HCl, human tumor necrosis factor apoptosis ligand TRAIL, bovine serum albumin BSA, polyethyleneimine PEI, carboxymethyl chitosan-folate conjugates CMCS-FA, water for injection and a crosslinking agent, and is a doxorubicin and TRAIL entrapped albumin nanoparticle targeting drug delivery system. The method comprises preparation of doxorubicin supported albumin nanoparticles, synthesis of a carboxymethyl chitosan-folate conjugate (CMCS-FA), and preparation of doxorubicin and TRAIL co-entrapped folate targeting albumin nanoparticles. Folic acid mediated active targeting and tumor pH sensitive release enhance the accumulation of drug carrier in tumors; the supported doxorubicin and TRAIL can produce synergistic anticancer effect and have a strong killing effect on cancer cells (including drug-resistant cells).

Description

technical field [0001] The invention relates to a drug-loaded preparation and a preparation method, in particular to an albumin nanoparticle targeting preparation and a preparation method of co-loading doxorubicin and TRAIL. Background technique [0002] According to the "Global Cancer Report 2014" released by the World Health Organization, the global cancer cases will show a rapid growth trend, from 14 million in 2012 to 19 million in 2025, and the number will increase to 24 million in 2035 people. Nearly half of the new cases are in Asia, most of which are in China. China has 3.07 million new cancer patients and 2.2 million deaths every year, accounting for 21.9% and 26.8% of the global total respectively. Therefore, the market for antineoplastic drugs has grown rapidly in recent years, with a compound growth rate of 7.2% globally from 2008 to 2013, and a compound growth rate of 20.4% in China, much higher than the global growth rate. [0003] The defect of current treat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K38/17A61K47/22A61K47/42A61P35/00A61K31/704
Inventor 张岩李洪仁李锋
Owner SHENYANG UNIV
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