Functional vinblastine lipidosome and application thereof

A technology of vinblastine and liposome, applied in the biological field, can solve the problems of recurrence and clearing of gliomas

Active Publication Date: 2018-04-06
PEKING UNIV
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In conventional chemotherapy, it is difficult for chemotherapeutic drugs to cross the blood-brain barrier, and a small amount of drugs that can cross the blood-brain barrier is also difficult to clear due to the drug resistance of glioma stem cells, resulting in the recurrence of glioma

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Functional vinblastine lipidosome and application thereof
  • Functional vinblastine lipidosome and application thereof
  • Functional vinblastine lipidosome and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0110] Embodiment 1, construction and characterization of functionalized vinblastine liposome

[0111] 1. Construction of functionalized vinblastine liposomes

[0112] 1. TfR-T 12 -PEG 2000 -Synthesis of DSPE

[0113] TfR-T 12 -PEG 2000 -DSPE is in the presence of a catalyst, the TfR-T 12 Peptides and NHS-PEG 2000 -DSPE is obtained by acylation reaction; where TfR-T 12 Peptides and NHS-PEG 2000 - The molar ratio of DSPE is 1:1.

[0114] The specific synthesis method is as follows:

[0115] Add 8 μmol TfR-T to the reaction vial 12 Peptide (THRPPMWSPVWP) and 8 μmol NHS-PEG 2000 -DSPE, dissolved with 2 mL of DMF, and added 200 μL of catalyst N-methylmorpholine. Stir and react at room temperature for 48 hours, then transfer to a dialysis bag (molecular weight cut-off: 3000 Da), place in deionized water and dialyze for 24 hours to remove solvent and unreacted raw materials. The samples were then freeze-dried and stored at -20°C.

[0116] The product was verified by ma...

Embodiment 2

[0182] Example 2, functionalized vinblastine liposomes on glioma and its stem cells targeted killing effector cell culture

[0183] 1. Cell culture

[0184] Glioma cell U87-MG cells were cultured in MEM medium containing 10% FBS and 1% non-essential amino acids at 37°C and 5% CO 2 .

[0185] Induction and culture of glioma stem cells (GSCs) (Yu SC; Ping YF; YiL; Zhou ZH; Chen JH; Yao XH; Gao L; Wang JM; Bian XW. Isolation and characterization of cancer stem cells from a human glioblastoma cell line U87[J].Cancer Letters,2008,265(1):124-34): 2×10 per mL 4 The concentration of U87-MG cells containing 2% Suspension culture in DMEM-F12 medium without serum supplement, 10ng / mL LIF, 20ng / mL EGF, 20ng / mL bFGF, 181.6ng / mL insulin, the culture condition is 37℃, containing 5% CO 2 . Identification was performed after four weeks in culture.

[0186] Rat brain capillary endothelial cells BMVECs were cultured in DMEM medium containing 20% ​​FBS, 100U / mL penicillin, 100μg / mL streptom...

Embodiment 3

[0209] Example 3, the effect of functionalized vinblastine liposomes across the blood-brain barrier

[0210] 1. Cell culture

[0211] Rat brain capillary endothelial cells BMVECs were cultured in DMEM medium containing 20% ​​FBS, 100U / mL penicillin, 100μg / mL streptomycin, 40U / mL heparin, 100ug / mL ECGF, the culture conditions were 37℃, containing 5% CO 2 . The flasks were treated with 2% gelatin solution 30 min in advance. The preparation method of 2% gelatin solution: weigh 2g gelatin, disperse and swell with 100ml Hank's solution (80°C), filter and sterilize, and store at 4°C.

[0212] 2. Transferrin receptor labeling on the surface of BMVECs

[0213] BSA buffer: Add 500 mg BSA and 74.45 mg EDTA per 100 mL of PBS buffer.

[0214] Collect BMVECs cells, add BSA buffer to resuspend the cells, divide the cells into 1.5mL EP tubes, add 1×10 7 cells. Add 5 μL Anti-Mouse Transferrin Receptor (CD71) antibody-FITC to the experimental group of BMVECs, and add 5 μL isotype contro...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
particle sizeaaaaaaaaaa
particle diameteraaaaaaaaaa
diameteraaaaaaaaaa
Login to view more

Abstract

The invention discloses a functional vinblastine lipidosome and an application thereof. The invention provides the vinblastine lipidosome which is prepared by the following steps: modifying a lipidosome with a functional material transferrin receptor combined peptide-polyethylene glycol-distearyl phosphatidyl ethanolamine and stearylated octaarginine to obtain a modified lipidosome; and then entrapping vinblastine to the modified lipidosome to obtain the functional vinblastine lipidosome. Experiments verify that the invention synthesizes the functional material transferrin receptor combined peptide-polyethylene glycol-distearyl phosphatidyl ethanolamine (NHS-PEG2000-DSPE) and modifies the vinblastine lipidosome with a targeting material stearylated octaarginine (stearyl-R8) so as to obtainthe functional vinblastine lipidosome capable of bestriding the blood brain barrier and killing glioma and stem cells thereof.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a functionalized vinblastine liposome and its application. Background technique [0002] Vinblastine (vinblastine, VLB) was first extracted and isolated from Apocynaceae periwinkle by scientists Robert Noble and Charles Thomas of the University of Western Ontario in Canada in 1958. It is a bis-indole alkaloid with antitumor properties. active. The structural formula of vinblastine is as follows figure 1 As shown, the molecular formula is C 46 h 58 N 4 o 9 , with a molecular weight of 810.97, often soluble in sulfate, insoluble in water, white or off-white crystalline powder. [0003] transferrin receptor binding peptide TfR-T 12 It is a polypeptide with the sequence THRPPMWSPVWP, comprising 12 amino acids (Thr-His-Arg-Pro-Pro-Met-Trp-Ser-Pro-Val-Trp-Pro), easily soluble in water and methanol, with a molecular weight of 1490.8. TfR-T 12 The polypeptide can specifically bind t...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/475A61K47/42A61K47/24A61K47/18A61P35/00
CPCA61K9/1271A61K31/475A61K47/183A61K47/24A61K47/34A61K47/42
Inventor 吕万良沐黎敏卜英子刘磊吴佳栓居瑞军
Owner PEKING UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap