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pH sensitive nanoparticles prodrug with capacity of co-delivering multiple drugs, preparation method and application thereof

A nanoparticle and co-delivery technology, applied in the fields of polymer chemistry and biomedical engineering, can solve the problems of toxic side effects, low drug loading, slow release rate, etc., to ensure the consistency of in vivo kinetics, improve drug loading capacity, The effect of enhancing stability

Inactive Publication Date: 2015-09-09
INST OF RADIATION MEDICINE CHINESE ACADEMY OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the drug loading capacity of traditional nanocarriers by physically loading drugs is generally very low, and the effective drug concentration must be delivered to the tumor by injecting high-concentration carriers or frequent injections, resulting in a large amount of carrier accumulation in the body that may cause unknown Toxic side effects and tumor drug resistance
At the same time, some carriers assembled by nanoprecipitation technology often lead to the "burst release" of some drugs after a few hours of injection into the body.
These prematurely released drugs will cause serious side effects to the body due to passive diffusion; at the same time, the secondary released drugs have significantly reduced anti-tumor activity due to their low concentration and slow release rate.

Method used

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  • pH sensitive nanoparticles prodrug with capacity of co-delivering multiple drugs, preparation method and application thereof
  • pH sensitive nanoparticles prodrug with capacity of co-delivering multiple drugs, preparation method and application thereof
  • pH sensitive nanoparticles prodrug with capacity of co-delivering multiple drugs, preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0047] figure 1 It is a schematic diagram of the pH-sensitive nanoparticle prodrug of the embodiment of the present invention. from figure 1 It can be seen from the figure that the double sensitive layer cross-linked nanoparticles of the present invention have a three-layer structure, the outer layer is PEG with high biocompatibility, the inner core is the anti-tumor drug DOX bonded to the hydrophilic end, and then wrapped by hydrophobic interaction Another hydrophobic antineoplastic drug Cur.

[0048] (a) Preparation of pH-sensitive nanoparticle prodrugs

[0049] Weigh 200 mg of mPEG-CHO (Methoxy-poly(ethylene glycol)-aldehyde) with a molecular weight of 2000 and 50 mg of doxorubicin (DOX), dissolve them in 2.0 mL of dimethyl sulfoxide (DMSO), add 20 μL of triethylamine was used as a catalyst, and the reaction was shaken in a water bath at 40 °C for 24 h. The solution was placed in a dialysis bag with a molecular weight cut-off of 1 KDa, and DMSO was used as the dialysat...

Embodiment 2

[0056] Sensitivity characterization of PEG-DOX-Cur NPs, the specific steps are as follows:

[0057] The prepared PEG-DOX-Cur NPs were placed in an acidic solution with pH 5.0 and incubated in a constant temperature oscillator at 37°C for 48 h, and the changes in particle size and morphology were detected by laser particle size analyzer and transmission electron microscope. Test results such as Figure 4 As shown in A, the particle size of the nanoparticle prodrug increased significantly at 24 h and 48 h, and the scanning electron microscope showed that the nanoparticle disintegrated at 48 h, and its shape was very irregular ( Figure 4 C).

Embodiment 3

[0059] The in vitro release behavior characterization of PEG-DOX-Cur NPs, the specific steps are as follows:

[0060] Take 5 mL of PEG-DOX-Cur NPs and encapsulate them in a dialysis bag with a molecular weight cut-off of 3500 Da, add 40 mL of dialysate, the dialysate is a phosphate buffer solution with a pH of 7.4, 6.5, and 5.0, and release it at a constant temperature of 37 °C. in the oscillator. At the predetermined time point, take out 5 mL of release solution and add the same volume of fresh release solution. The amount of drug released was measured by UV spectrophotometer.

[0061] The evaluation results of release behavior are as follows: Figure 5 As shown, DOX and Cur exhibit similar release curves, because the Schiff base bond is an acid-responsive cleavage bond, which leads to the cleavage between PEG and DOX, and the hydrophobic interaction between the nanoparticle prodrug and Cur disappears, that is, in When the nanoparticle prodrug disintegrates, all loaded dru...

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Abstract

The invention relates to a pH sensitive nanoparticles prodrug with capacity of co-delivering multiple drugs, a preparation method and an application thereof. According to the invention, an external layer is polyethylene glycol possessing highly biological compatibility, a core is hydrophilic terminal bond and an antitumor drug doxorubicin (DOX), and the other hydrophobic antitumor drug curcumin (Cur) is coated through a hydrophobic effect. A structure is PEG-DOX-W-NPs. Under pH response condition, the nanoparticles prodrug can simultaneously release multiple antitumor drugs through disintegration for performing combination therapy effect. The provided pH sensitive nanoparticles prodrug has the advantages of good biology compatibility and long internal effect time. The preparation method has the advantages of simple process, good stability, and convenient operation and popularization.

Description

technical field [0001] The invention relates to the technical fields of polymer chemistry and biomedical engineering, and relates to a pH-sensitive nanoparticle prodrug capable of loading multiple chemotherapeutic drugs, in particular a pH-sensitive nanoparticle prodrug capable of co-delivering multiple drugs and its preparation method and application . Background technique [0002] Traditional chemotherapy is subject to multiple limitations in the treatment of cancer diseases. Small molecule antineoplastic drugs are often used as chemotherapy agents in the clinical treatment of glioma diseases, but due to their own physical and chemical properties, they have poor bioavailability and poor blood / kidney clearance. Problems such as high rate, poor specificity, low tumor accumulation concentration, high toxicity and side effects, and tumor multidrug resistance severely limit its clinical application. Clinically, it is necessary to increase the dosage to meet the effective conce...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00A61K47/48A61K47/34A61K31/704A61K45/06A61P35/00A61K31/12A61K31/337A61K31/4745A61K31/475A61K31/573A61K38/14
Inventor 刘鉴峰张玉民褚丽萍刘金剑杨翠红高红林
Owner INST OF RADIATION MEDICINE CHINESE ACADEMY OF MEDICAL SCI
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