Tumor-targeted double-drug-delivery nano carrier and preparation method thereof

A nanocarrier, tumor targeting technology, applied in the field of biomedical engineering materials, can solve the problems of uncontrollable drug release, low tumor specificity, high cytotoxicity, etc., to improve drug effect, low cytotoxicity, tumor targeting strong effect

Inactive Publication Date: 2017-10-20
广州博徕斯生物科技股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing polymer self-assembled nanosystems still have problems such as low tumor specificity, high cytotoxicity, slow biodegradation, and uncontrollable drug release, which limit their application.

Method used

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  • Tumor-targeted double-drug-delivery nano carrier and preparation method thereof
  • Tumor-targeted double-drug-delivery nano carrier and preparation method thereof
  • Tumor-targeted double-drug-delivery nano carrier and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1: Preparation of dihydroxy polycaprolactone (PCL) with disulfide bonds

[0040] Dissolve cystamine and ε-caprolactone with disulfide bonds in dry toluene, slowly add the catalyst stannous isooctanoate dropwise for 20 minutes under anhydrous and oxygen-free conditions, and condense at 110°C in a nitrogen environment after the dropwise addition Reflux reaction for 18 hours, magnetic stirring during the reaction, and the rotation speed was 300rpm; after the reaction was completed, the toluene solvent was removed by rotary evaporation at 40°C, and then precipitated with cold ether, and then vacuum-dried at 40°C for 12h to obtain dihydroxypolycaprolactone with a disulfide bond (PCL).

[0041] Wherein, the quality of cystamine is 200mg; The total volume of toluene is 10mL; The mol ratio of cystamine, ε-caprolactone, stannous isooctanoate is 1:132:0.05; The volume ratio of cold ether and reaction system solution is 10 :1.

[0042] The prepared dihydroxy polycaprolac...

Embodiment 2

[0043] Example 2: Preparation of acrylate-terminated dihydroxypolycaprolactone (PCL-Acrylate):

[0044] Dissolve triethylamine and acryloyl chloride in dry toluene, respectively, and first vacuum and blow nitrogen into the dihydroxy polycaprolactone (PCL) having a disulfide bond prepared in Example 1, and then successively add triethylamine and The toluene solution of acryloyl chloride was slowly added dropwise for 30 minutes in an ice bath and protected from light; condensed and refluxed at 80°C for 8 hours, magnetically stirred at a speed of 300rpm during the reaction, after the reaction, the reaction solution was filtered to remove triethylamine hydrochloride After crystallization, the filtrate was precipitated in excess cold n-hexane, filtered by suction, and the white powder product was collected, and finally vacuum-dried at 40°C for 24 hours to obtain acrylate-terminated dihydroxy polycaprolactone (PCL-Acrylate).

[0045] Wherein, the quality of the dihydroxy polycaprola...

Embodiment 3

[0047] Example 3: Preparation of polycaprolactone-poly(amide-amine) polymer (PCL-PAMAM)

[0048] The polyamide-amine dendrimer (PAMAM) and the acrylate-terminated bishydroxypolycaprolactone (PCL-Acrylate) prepared in Example 2 were dissolved in chloroform respectively, and the polyamide-amine dendrimer (PAMAM) was completely dissolved at 55°C under a nitrogen atmosphere, and then the chloroform solution of acrylate-terminated bishydroxypolycaprolactone (PCL-Acrylate) was slowly added dropwise to the polyamide-amine dendrimer ( In the chloroform solution of PAMAM), vacuumize, nitrogen flow, reflux reaction at 55 ℃ for 24h, magnetic stirring during the reaction, the rotating speed is 300rpm; Days, dialyze unreacted monomers, and precipitate with excess cold petroleum ether to obtain a white precipitate, dissolve it with a small amount of dichloromethane, slowly add it dropwise to deionized water, stir overnight, evaporate the organic solvent, and freeze-dry After 48 hours, the ...

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Abstract

The invention discloses a tumor-targeted double-drug-delivery nano carrier and a preparation method thereof. The tumor-targeted double-drug-delivery nano carrier is a cationic polymer nano carrier assembled from polycaprolactone, polyamidoaminedendrimer, polyethylene glycol and polypeptide. The carrier can deliver a chemotherapy drug and a gene drug to tumor tissue in a targeting mode at the same time, and has the advantages of high drug entrapment efficiency, strong tumor targeting, low cytotoxicity, and the like.

Description

technical field [0001] The invention belongs to the field of biomedical engineering materials, and in particular relates to a tumor-targeting double-loaded drug nanocarrier and a preparation method thereof. Background technique [0002] According to statistics, malignant tumors are the second largest killer after cardiovascular and cerebrovascular diseases. At present, the vast majority of patients are treated by surgical resection, radiotherapy and chemical drugs. These therapies can obtain rapid and effective therapeutic effects on patients with early-stage tumors, but for patients with advanced tumors accompanied by local spread and metastasis, they have not significantly prolonged the survival period and improved the quality of life of patients, and have relatively large toxic and side effects. In recent years, studies have found that cancer is a genetic disease, which is a multi-stage long-term evolution process in which various pre-oncogenes are activated and tumor sup...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K47/69A61K47/60A61K47/64A61P35/00C08G81/00C08G63/91C08G63/688
CPCA61K9/5153C08G63/6882C08G63/912C08G81/00
Inventor 李然刘晋峰
Owner 广州博徕斯生物科技股份有限公司
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