Targeting nanometer drug delivery system aiming at glioma

A nano-drug delivery system, glioma technology, applied in anti-tumor drugs, capsule delivery, micro-capsules, etc., can solve the problems of normal tissue cytotoxicity, short half-life of fusion protein, less drug distribution, etc. Glioma effect, realization of targeted therapy, effect of promoting uptake

Active Publication Date: 2014-03-12
FUDAN UNIV
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

[0005] Although the construction of fusion proteins to achieve targeted therapy of glioma is a relatively recognized method in the industry, there are still the following disadvantages: (1) Fusion proteins may reduce the affinity between IL13 and IL13Rα2, and may also reduce the activity of toxin proteins ; (2) The stable expression and purification of the fusion protein is difficult and the production cost is high; (3) There are many IL13 receptors, and the fusion protein may target non-target cells, causing toxic side effects on normal tissue cells; (4) The half-life of the fusion protein is short in vivo after intravenous injection, and the distribution of the drug in the tumor site is less
At present, there are no reports on the treatment of glioma with IL13 peptide modified nano-drug delivery system at home and abroad

Method used

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  • Targeting nanometer drug delivery system aiming at glioma
  • Targeting nanometer drug delivery system aiming at glioma
  • Targeting nanometer drug delivery system aiming at glioma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1 Preparation and Characterization of IL13 Peptide Modified Nanoparticles (ILNP)

[0026]Nanoparticles were prepared by emulsifying lysozyme evaporation method, accurately weighed 1.0mg DTX, 28.0mg methoxy-PEG-PCL, 2.0mg carboxyl-PEG-PCL, dissolved in 1ml dichloromethane, and added 5ml 0.6% cholic acid Sodium, sonicate in an ice-water bath for 5s, stop for 5s, 20 times in total, remove dichloromethane by rotary steaming at 37°C for 15min, and concentrate to 1mL by centrifugal ultrafiltration at 3500rpm and 4°C. Use 2-morpholineethanesulfonic acid (MES) buffer (pH 6.0) to desalt through a Hitrap desalting column and replace the outer aqueous phase, add 4 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide Hydrochloride (EDC) and 6 mg N-hydroxysuccinimide (NHS) were activated for 20 minutes, desalted through a Hitrap desalting column and replaced with 0.01 mol / L phosphate buffer (PBS, pH 7.4). Add 20 μg of IL13 peptide, react for 6 hours, wash through Sepharose CL...

Embodiment 2

[0027] Example 2 In vitro glioma cell apoptosis test

[0028] U87 cells were inoculated on a 6 cm culture plate and cultured for 24 hours. When the confluence of the cells reached about 80%, ILNP containing DTX at a concentration of 500 ng / mL was added and cultured for 24 hours. The cells were digested, the cells were stained with an apoptosis detection kit (containing annexinV-FITC and propidium iodide 50 μg / mL), and the early and late apoptosis rates of the cells were detected by flow cytometry. The results of apoptosis detected by flow cytometry are shown in Table 1. In the control group, U87 cells had little early and late apoptosis. Compared with the control group, the early and late apoptosis rates of cells were significantly increased after NP, ILNP, and DTX treatment, and the total apoptosis rate of cells was significantly increased. Among them, the total apoptosis rates of cells treated by NP and ILNP groups were significantly higher in the DTX group. Table 1 is the...

Embodiment 3

[0032] Example 3 In vitro growth inhibition test of U87 tumor spheres

[0033] U87 cells were inoculated into agarose-coated 6-well culture plates and cultured for 7 days to grow into avascular tumorspheres. ILNP containing DTX at a concentration of 2500 ng / mL was added to culture for 5 days, the volume of tumor spheres was measured every day, and the volume change of tumor spheres was calculated with the initial volume of tumor spheres at the time of administration as a reference. After the treatment, the tumor spheres were fixed with 2.5% glutaraldehyde, and the surface morphology of the tumor spheres was observed with a scanning electron microscope. The result is as figure 2 As shown in A, the growth of tumor spheres in the control group was faster. Compared with the control group, the growth of tumor spheres was significantly inhibited after treatment with NP, ILNP, and DTX. The volume of tumor spheres in the ILNP group was significantly lower than that in the NP and DTX...

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Abstract

The invention belongs to the field of medicine preparation, and in particular to a targeting nanometer drug delivery system aiming at glioma, and a preparation method and application thereof. The drug delivery system comprises target functional molecules, a drug and nano carriers. The target functional molecules are from short chain polypeptide from interleukin 13; the drug is a micromolecular anti-glioma drug; the nano carriers are liposome with surface modified by polyethylene glycol, nanoparticles, polymeric vesicles, polymer micelles and solid lipid nanoparticles; and the drug is enveloped in the nano carriers in an enveloping or covalent connection manner, and the short chain polypeptide is connected with the polyethylene glycol on the surfaces of the nanoparticles through covalent connection. The drug delivery system can promote uptake of the glioma cells by mediated effect of an interleukin 13 receptor alpha 2 on the surfaces of the glioma cells, so as to improve the effect of anti-glioma chemotherapeutics.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to the research on tumor targeted drug delivery, in particular to a targeted nanometer drug delivery system for brain glioma, its preparation method and application. Background technique [0002] Malignant glioma has become one of the major brain diseases that affect human health. According to statistics, it has a high mortality rate. The 5-year survival rate of adult malignant glioma is less than 5%, but there is no effective cure. For malignant glioma, the traditional treatment method is surgical resection of the tumor followed by chemotherapy with antineoplastic drugs. However, surgical resection is very risky, and most traditional anti-tumor drugs are not selective, and can kill normal cells while killing tumor cells, causing serious side effects and limiting their application. [0003] At present, the nano-targeted drug delivery system is one of the hot spots in the r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K9/127A61K9/51A61K47/42A61P35/00A61K47/34
Inventor 庞志清高会乐蒋新国沈顺钱勇魏彦
Owner FUDAN UNIV
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