A visual microvesicle composition carrying adriamycin and a preparing method thereof

A compound, adriamycin technology, applied in the field of anti-tumor drugs, can solve the problems of poor tumor targeting effect and drug release ability, and achieve the effect of improving chemotherapy effect, promoting uptake, and improving targeting ability

Active Publication Date: 2016-11-30
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the complexity of the in vivo environment in further in vivo applications, the tumor targeting effect and drug release ability of the complex system are not good when applied in vivo

Method used

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  • A visual microvesicle composition carrying adriamycin and a preparing method thereof
  • A visual microvesicle composition carrying adriamycin and a preparing method thereof
  • A visual microvesicle composition carrying adriamycin and a preparing method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] 1. Preparation of visualized microbubble complexes

[0026] (1) Dissolve PEG 0.1mmol and cRGD 0.2mmol in anhydrous DMF, add catalyst EDC 0.2mmol and triethylamine 0.1mmol and react at 50°C for 12h. Remove excess anhydrous DMF by rotary evaporation, add TFA until the pH value is 5.0 (10ml), react at room temperature for 1 hour, remove TFA by rotary evaporation, adjust the pH value to neutral by adding triethylamine dropwise, and rotate again to obtain the intermediate product PEG- cRGD;

[0027] (2) Dissolve succinic anhydride-heparin 50mg, aminated folic acid 6mg, aminated biotin 4.5mg and PEG-cRGD (2mgcRGD) in anhydrous DMSO, add catalyst EDC 14mg and NHS 11mg, react at room temperature for 24h and place Dialyze in the dialysis membrane for 48h. Add 2 mg of ADH and 4 mg of EDC to double-distilled water and react at room temperature for 6 hours, add 6 mg of doxorubicin, adjust the pH value to 5.0 with glacial acetic acid, react at room temperature for 12 hours, adjust...

Embodiment 2

[0033] 1. Preparation of visualized microbubble complex, monoligand acid-sensitive doxorubicin prodrug and double-ligand acid-sensitive doxorubicin prodrug

[0034] (1) The dual-ligand acid-sensitive doxorubicin prodrug and visualized microbubble complex was prepared according to the steps in Example 1.

[0035] (2) The monoligand acid-sensitive doxorubicin prodrug H-F-DOX was prepared according to the same method as in steps (1) and (2) of Example 1, wherein the aminoated folic acid was omitted in step (2).

[0036] (3) The monoligand acid-sensitive doxorubicin prodrug H-RGD-DOX was prepared according to the same method as in steps (1) and (2) of Example 1, wherein PEG-cRGD was omitted in step (2).

[0037] 2. Detection of cellular uptake ability of visualized microbubble complexes

[0038] (1) Flow cytometric uptake experiments comparing the uptake of monoligand acid-sensitive doxorubicin prodrugs H-F-DOX, H-RGD-DOX and double-ligand acid-sensitive doxorubicin prodrugs H-F-...

Embodiment 3

[0040] Example 3 (Visualization of Cytotoxicity Detection of Microvesicle Complexes)

[0041] 1. Take the double-ligand acid-sensitive doxorubicin prodrug and visualized microbubble complex prepared in Example 1.

[0042] 2. MTT cytotoxicity test compares the killing effect of free doxorubicin, double-ligand acid-sensitive doxorubicin prodrug and the visualized microbubble complex combined with ultrasound on MCF-7 breast cancer cells. The results showed that, compared with the free doxorubicin group, the dual-ligand acid-sensitive doxorubicin prodrug group and the visualized microbubble complex group combined with ultrasound showed stronger killing effects, and the visualized microbubble complex combined with ultrasound The compound group has the strongest killing ability to MCF-7 breast cancer cells. The ranking of its LD50 is: combined ultrasound-assisted visualized microbubble complex group image 3 shown).

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Abstract

The invention relates to a visual microvesicle composition carrying adriamycin. The composition is formed by connecting dual-ligand acid-sensitive adriamycin prodrug groups to the surface of a biotinylated lipid microvesicle through an avidin intensive bridging manner, wherein the chemical structure of each dual-ligand acid-sensitive adriamycin prodrug group is shown as a following formula (I). The composition can promote adriamycin release in a tumor acidic microenvironment, can enhance a targeting function, and can exert a function of real-time ultrasonic tumor targeting imaging.

Description

technical field [0001] The invention relates to antitumor drugs, in particular to antitumor drugs characterized by carriers. Background technique [0002] Doxorubicin is an anthracycline antineoplastic drug commonly used in clinical practice. However, its clinical application is limited because it can cause various toxic and side effects such as cardiotoxicity, nephrotoxicity, bone marrow suppression, hair loss and gastrointestinal reactions. Therefore, it is of great significance for the treatment of tumors to modify doxorubicin to prepare a drug-loading system to improve the curative effect and reduce the side effects. [0003] Ultrasound-targeted microbubble destruction technology is an effective drug delivery aid that can facilitate site-specific release of drugs. Inertial cavitation such as microacoustic flow, shock wave and microjet produced by microbubble rupture can increase the endothelial gap and cell membrane permeability, which can effectively increase drug upt...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K31/704A61P35/00
CPCA61K31/704
Inventor 李颖嘉王莺罗婉贤文戈杨莉
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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