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Multifunctional targeting drug delivery system with combined action of chemotherapy and phototherapy and preparation method thereof

A technology of targeted drug delivery and combined action, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, etc. Treatment effects and other issues, to achieve the effect of solving multidrug resistance, enhancing anti-tumor efficacy, and reducing toxic and side effects

Active Publication Date: 2019-08-30
深圳禾义科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Commonly used photosensitizers are mostly water-insoluble molecules (such as Ce6), which are easy to aggregate and lack targeting to the tumor site, making it difficult to deliver to the tumor site in vivo and enrich to an effective concentration, thereby affecting the therapeutic effect

Method used

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  • Multifunctional targeting drug delivery system with combined action of chemotherapy and phototherapy and preparation method thereof
  • Multifunctional targeting drug delivery system with combined action of chemotherapy and phototherapy and preparation method thereof
  • Multifunctional targeting drug delivery system with combined action of chemotherapy and phototherapy and preparation method thereof

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preparation example Construction

[0031] 1) Preparation of Ce6@PDA

[0032] Dissolve 20 mg PLGA and 2 mg Ce6 in 1 mL of acetone, and add them dropwise to 20 mL of deionized water under constant stirring in the dark, stir for 12 hours to remove acetone, centrifuge and wash with de-ethanol and deionized water to remove free Ce6, freeze-dry to obtain Ce6 / PLGA NP, disperse 50mgCe6 / PLGA NP in 50mL Tris-HCl buffer (pH8.5, 10mM), add 50mg dopamine hydrochloride, stir for 4 hours in the dark, then centrifuge the mixture and wash it three times with deionized water to remove untreated Polymerized dopamine was freeze-dried to obtain Ce6@PDA.

[0033] 2) HA-NH 2 Synthesis

[0034] Weigh 50mgHA, 145.6mgEDC.HCl, 88mgNHS, dissolve in 15mL formamide, activate the carboxyl group of HA under nitrogen protection, then slowly add it dropwise to ice-cold 10mL formamide solution containing 2.704mmol ethylenediamine, under nitrogen environment The reaction was stirred for 24 hours, and the reaction solution was precipitated in ex...

Embodiment 2

[0040] 1) Preparation of Ce6@PDA

[0041] Dissolve 30mgPLGA and 2mgCe6 in 1mL of acetone, and add it dropwise to 20mL of deionized water under constant stirring in the dark, stir for 12 hours to remove acetone, centrifuge and wash with de-ethanol and deionized water to remove free Ce6, freeze-dry to obtain Ce6 / PLGA NP, disperse 50mgCe6 / PLGA NP in 50mL Tris-HCl buffer (pH8.5, 10mM), add 50mg dopamine hydrochloride, stir for 6 hours in the dark, then centrifuge the mixture and wash it three times with deionized water to remove untreated Polymerized dopamine was freeze-dried to obtain Ce6@PDA.

[0042] 2) HA-NH 2 Synthesis

[0043] Weigh 50mgHA, 145.6mgEDC.HCl, 88mgNHS, dissolve in 15mL formamide, activate the carboxyl group of HA under nitrogen protection, then slowly add it dropwise to ice-cold 10mL formamide solution containing 2.704mmol ethylenediamine, under nitrogen environment The reaction was stirred for 24 hours, and the reaction solution was precipitated in excess c...

Embodiment 3

[0049] 1) Preparation of Ce6@PDA

[0050] Dissolve 30mgPLGA and 2mgCe6 in 1mL of acetone, and add it dropwise to 20mL of deionized water under constant stirring in the dark, stir for 12 hours to remove acetone, centrifuge and wash with de-ethanol and deionized water to remove free Ce6, freeze-dry to obtain Ce6 / PLGA NP, disperse 50mgCe6 / PLGA NP in 50mL Tris-HCl buffer (pH8.5, 10mM), add 50mg dopamine hydrochloride, stir in the dark for 8 hours, then centrifuge the mixture and wash it with ethanol and deionized water in sequence to The unpolymerized dopamine was removed, and Ce6@PDA was obtained by freeze-drying.

[0051] 2) HA-NH 2 Synthesis

[0052] Weigh 50mgHA, 145.6mgEDC.HCl, 88mgNHS, dissolve in 15mL formamide, activate the carboxyl group of HA under nitrogen protection, then slowly add it dropwise to ice-cold 10mL formamide solution containing 2.704mmol ethylenediamine, under nitrogen environment The reaction was stirred for 24 hours, and the reaction solution was pre...

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Abstract

The invention discloses a multifunctional targeting drug delivery system with combined action of chemotherapy and phototherapy and a preparation method thereof. The method comprises the following steps: preparation of drug-loaded nanoparticles; synthesis of HA-NH2; synthesis of DOX-ss-HA-NH2; and preparation of a targeting drug delivery system Ce6@PDA-HA-ss-DOX. The multifunctional targeting drugdelivery system disclosed by the invention has good biocompatibility, biodegradability and low toxicity, and can respond to the biological characteristics of low pH environment, high glutathione concentration and high CD44 receptor expression of tumor cells to release drugs. The chemotherapy is carried out together with photothermal therapy and photodynamic therapy so as to obviously improve the killing effect on the tumor cells, and to provide a better treatment method for tumor.

Description

technical field [0001] The invention relates to the technical field of material preparation and drug controlled release, in particular to a multifunctional targeted drug delivery system with combined effects of chemotherapy and phototherapy and a preparation method thereof. Background technique [0002] Cancer, also known as malignant tumor, is a disease caused by the abnormal mechanism of controlling cell growth and proliferation. Cancer is a major problem worldwide, and the global cancer-related burden continues to increase. At present, chemotherapy is still the main means of cancer treatment. Chemotherapy drugs are powerful and can quickly kill or kill tumor cells, and play an important role in clinical treatment. However, chemotherapy drugs generally have problems such as poor cell selectivity, large toxic and side effects, serious adverse reactions, and multidrug resistance, which make it difficult for drugs to exert their best curative effect. Therefore, targeting tu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K31/704A61K47/69A61P35/00
CPCA61K31/704A61K41/0052A61K41/0071A61K47/6935A61K47/6939A61P35/00A61K2300/00
Inventor 许沛虎宁偲偲徐海星黄志军张婉婷李锐王娜方雪婷李泽马毓聪闫秀美
Owner 深圳禾义科技有限公司
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