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Targeting hybrid nano-system, preparation method thereof and application

A targeted and nanosphere technology, applied in the field of nanomaterials, can solve the problems of inability to enter tumor tissue and reduce the penetration of nanoparticle concentration into tumor tissue, so as to increase drug delivery dose, enhance targeting effect, and increase penetration Effect

Active Publication Date: 2017-11-03
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, in this liposome-polymer hybrid nanoparticle, a layer of phospholipid bilayer is attached to the surface of each polymer nanoparticle, although it can realize the loading of different drugs, but it reduces the concentration of nanoparticles and the effect on tumor tissues. The penetration effect in the tumor tissue cannot achieve the purpose of entering the deep part of the tumor tissue

Method used

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  • Targeting hybrid nano-system, preparation method thereof and application
  • Targeting hybrid nano-system, preparation method thereof and application
  • Targeting hybrid nano-system, preparation method thereof and application

Examples

Experimental program
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Effect test

Embodiment 1

[0063] A nanohybrid system of liposomes entrapped with multiple polymer nanoparticles was prepared by double emulsion method, film dispersion method and extrusion method, and the surface of the hybrid system can be targeted to the EDB domain of fibronectin in the tumor microenvironment . In this system, the hydrophobic TGF-β inhibitor TEW7197 is carried between the bilayer structure of the liposome membrane, and the hydrophobic chemotherapeutic drug paclitaxel is carried in the small polymer nanoparticle.

[0064] Its preparation method comprises the following steps:

[0065] (1) Preparation of liposome film

[0066] Weigh 12.5 mg of soybean lecithin, 4.6 mg of cholesterol, 1.8 mg of phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) and 1 mg of phosphatidylethanolamine-polyethylene glycol-maleimide (DSPE-PEG-Mal) . Take by weighing medicine TEW71970.2mg at the same time, all materials and medicine are dissolved in 5mL dichloromethane solution jointly, slowly rotate in...

Embodiment 2

[0078] A nano-hybrid system in which liposomes entrap multiple polymer nanoparticles was prepared by double-emulsion method, film dispersion method and extrusion method, and the surface of the hybrid system can target FAP- alpha. In this system, hydrophobic vitamin D derivative calcipotriol (Calcipotriol) is carried between the bilayer structure of the liposome membrane, and the hydrophilic chemotherapy drug gemcitabine is carried inside the small polymer nanoparticle.

[0079] Its preparation method comprises the following steps:

[0080] (1) Preparation of liposome film

[0081] Weigh 6.3 mg of soybean lecithin, 2.3 mg of cholesterol, 0.9 mg of phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) and 0.5 mg of phosphatidylethanolamine-polyethylene glycol-succinimide ester (DSPE-PEG-NHS) mg. Take medicine calcipotriol 0.2mg simultaneously, all materials and medicine are dissolved in 5ml dichloromethane solution jointly, slowly rotate into the liposome film of monolayer ...

Embodiment 3

[0093] The targeted nano-hybrid system obtained in Example 1 was dispersed in 1 mL of PBS buffer solution with pH of 7.4, 6.5 and 4.2 and placed in a dialysis bag, and the dialysis bag was placed in 40 mL of buffer solution with corresponding pH The buffer solution outside the dialysis bag was continuously stirred in the middle, and a certain volume of buffer solution was taken out from the external 40mL buffer solution at different time points and a corresponding volume of buffer solution was added at the same time. The removed buffer solution was lyophilized and redissolved in acetonitrile. The drug concentration in the buffer solution at each time point was detected by high performance liquid chromatography, and the release efficiency of TEW7197 and paclitaxel was calculated, and the release curves of the two drugs were drawn. Calculated as follows:

[0094]

[0095] Among them, m t is the total amount released at each time point (t), C t is the solution concentration ...

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Abstract

The invention provides a targeting hybrid nano-system, a preparation method thereof and an application. The targeting hybrid nano-system comprises lipid bilayer nanospheres, amphipathic polymeric nano-particles, targeting polypeptides and / or antibodies and different medicines, wherein the lipid bilayer nanospheres wrap the amphipathic polymeric nano-particles, the targeting polypeptides and / or antibodies are connected on the surfaces of the lipid bilayer nanospheres, and the amphipathic polymeric nano-particles and the lipid bilayer nanospheres wrap the different medicines. The prepared targeting hybrid nano-system has targeting according to tumor microenvironments and has a space structure of 'a large sphere wrapping a small sphere', small nano-particles in the system have penetrating capacity for deep tumor tissues, the targeting hybrid nano-system can simultaneously wrap various different water-soluble medicines, and multi-drug combination treatment targeting tumor tissues is achieved, so that the targeting hybrid nano-system has the advantages of good specificity and drug loaded effect, moderate drug release speed, multi-drug combination and multi-targeted treatment.

Description

technical field [0001] The invention belongs to the technical field of nanomaterials, and relates to a targeted hybrid nano system and its preparation method and application, in particular to a hybrid system in which liposomes targeting tumor tissues carry multiple polymer nanoparticles And its preparation method and application. Background technique [0002] Cancer treatment mainly includes chemotherapy, radiation therapy and surgical resection. Among them, chemotherapy basically runs through the entire treatment process of all cancer types. Traditional chemotherapy uses small molecule chemotherapy drugs. Due to the high matrix and low blood supply environment of the tumor site, the chemotherapy drugs that actually reach the tumor site are very limited and metabolized rapidly. At the same time, due to the complex self-repair and defense mechanisms of malignant tumor cells, after a certain course of chemotherapy, tumor cells will develop drug resistance and lead to tumor gr...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/66A61K47/68A61K47/34A61K31/337A61K31/593A61K31/7068A61K31/444A61P35/00
CPCA61K31/337A61K31/444A61K31/593A61K31/7068A61K47/34A61K2300/00A61K9/0087A61K9/1271A61K9/5146A61K9/5153A61K9/5169A61K31/00
Inventor 聂广军杨霄李一叶金圣镇魏景艳
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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