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Antileukemie GSH/pH responsive nanometer drug delivery system and preparation method thereof

A drug delivery system and responsive technology, applied in the field of GSH/pH-responsive nano drug delivery system and its preparation, can solve the problems of refractory degradation and unsuitability of sodium alginate, etc., to improve water solubility, reduce drug resistance, To achieve the effect of stability

Inactive Publication Date: 2019-01-11
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the rigid molecular chain of sodium alginate, it is difficult to degrade in vivo, which makes sodium alginate not suitable as a drug carrier

Method used

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  • Antileukemie GSH/pH responsive nanometer drug delivery system and preparation method thereof
  • Antileukemie GSH/pH responsive nanometer drug delivery system and preparation method thereof
  • Antileukemie GSH/pH responsive nanometer drug delivery system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] (1) Preparation of Aldehyde Sodium Alginate (DSA):

[0043] Take 1.00g sodium alginate (SA) and add it into 20mL deionized water, heat and stir to dissolve it. Cool to room temperature, and use a volumetric flask to make up to 100ml. Weigh 1.0796 g of sodium periodate, add it into an Erlenmeyer flask and react with the sodium alginate solution for 24 hours under the condition of shielding from light and magnetic stirring. Then add a few drops of anhydrous ethylene glycol to stop the reaction. After standing for 2 hours, add absolute ethanol and a little NaCl solid, stir and let stand until flocculent precipitation appears. Filtrate under reduced pressure, wash twice with a little ethanol, and freeze-dry at -34°C to obtain aldehyde sodium alginate. The degree of oxidation is 80%.

[0044] (2) Preparation of 6-mercaptoguanine-formyl sodium alginate polymer prodrug:

[0045] Weigh 0.01g of the prepared aldehyde sodium alginate and dissolve it in 2ml of deionized water. A...

Embodiment 2

[0049] (1) Preparation of Aldehydic Sodium Alginate (DSA)

[0050] Take 1.00g sodium alginate (SA) and add it into 20mL deionized water, heat and stir to dissolve it. Cool to room temperature, and use a volumetric flask to make up to 100ml. Weigh 1.0796 sodium periodate, add it into a Erlenmeyer flask and react with sodium alginate solution for 24 hours under the condition of shielding from light and magnetic stirring. Then add a few drops of anhydrous ethylene glycol to stop the reaction. After standing for 2 hours, add absolute ethanol and a little NaCl solid, stir and let stand until flocculent precipitation appears. Filtrate under reduced pressure, wash twice with a little ethanol, and freeze-dry at -34°C to obtain aldehyde sodium alginate. The degree of oxidation is 80%.

[0051] (2) Preparation of 6-mercaptoguanine-aldehyde sodium alginate polymer prodrug

[0052] Weigh 0.02g of the prepared aldehyde sodium alginate and dissolve it in 2ml of deionized water. At the s...

Embodiment 3

[0056] (1) Preparation of Aldehydic Sodium Alginate (DSA)

[0057] Take 1.00g sodium alginate (SA) and add it into 20mL deionized water, heat and stir to dissolve it. Cool to room temperature, and use a volumetric flask to make up to 100ml. Weigh 0.499 g of sodium periodate, add it into an Erlenmeyer flask and react with the sodium alginate solution for 24 hours under the condition of shielding from light and magnetic stirring. Then add a few drops of anhydrous ethylene glycol to stop the reaction. After standing for 2 hours, add absolute ethanol and a little NaCl solid, stir and let stand until flocculent precipitation appears. Filtrate under reduced pressure, wash twice with a little ethanol, and freeze-dry at -34°C to obtain aldehyde sodium alginate. The degree of oxidation is 60%.

[0058] (2) Preparation of 6-mercaptoguanine-aldehyde sodium alginate polymer prodrug

[0059] Weigh 0.01g of the prepared aldehyde sodium alginate and dissolve it in 2ml of deionized water....

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Abstract

The invention relates to an antileukemie GSH / pH responsive nanometer drug delivery system and a preparation method thereof. A cross-linking compound of hydrophobic antineoplastic drug 6-thioguanine and biodegradable aldehyde sodium alginate is an active ingredient of the system. The system is prepared according to the following steps: oxidizing sodium alginate with sodium periodate, thereby acquiring aldehyde sodium alginate; grafting 6-thioguanine onto the molecular chain of aldehyde sodium alginate through schiff base reaction, thereby acquiring a pH responsive polymer prodrug; and acquiringdisulfide bond cross-linking polymer prodrug micelle in the manner of ultrasonically-assisted self-assembling in a buffer solution, thereby endowing particles with GSH and pH responsiveness. The preparation method provided by the invention is simple, is capable of promoting water solubility of 6-thioguanine and inhibition ratio of tumor cells, is capable of reducing toxic or side effect of normalcells and is expected to achieve the purpose of obviously promoting the therapeutic effect of chemotherapeutic drugs for leukemia.

Description

technical field [0001] The invention relates to an intelligent nanometer drug delivery system, in particular to a GSH / pH responsive nanometer drug delivery system for anti-leukemia and a preparation method thereof. Background technique [0002] In recent years, polymeric prodrug nano-drug delivery systems have attracted extensive attention due to their easily optimized structural features. The polymer prodrugs prepared by grafting hydrophobic drugs onto hydrophilic macromolecules can form a single-component nano drug delivery system through self-assembly, which has the following advantages: (1) improve the water solubility of hydrophobic drugs; (2) ) Avoid premature drug leakage and prevent drug degradation and inactivation in the blood; (3) prolong the blood circulation time of drugs; (4) enhance the selective release of drugs in targeted tissues and cells; (5) improve drug loading capacity (6) Improve drug bioavailability; (7) Enhance the passive targeting of drugs at tum...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/04A61K47/61A61K9/107A61K31/52A61P35/02
CPCA61K9/1075A61K31/52A61K47/61A61P35/02C08B37/0084
Inventor 殷以华潘茜赵铭洲万燕鸣郑丽敏杨梦丹吴杰郑化何梦
Owner WUHAN UNIV OF TECH
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