Folate-mediated targeted polymeric micelle

A technology of polymer glue and folic acid, which is applied in the direction of drug combination, drug delivery, and medical preparations of non-active ingredients, etc. It can solve the problems of phagocytosis of drug-loaded micelles, reduce the effect of targeting tumor cells, and reduce drug efficacy.

Inactive Publication Date: 2010-06-09
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, an excess of folic acid molecules will cause the drug-loaded micelles to be phagocytized by macrophages, thereby reducing the effect of targeting tumor cells and reducing drug efficacy.

Method used

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  • Folate-mediated targeted polymeric micelle
  • Folate-mediated targeted polymeric micelle
  • Folate-mediated targeted polymeric micelle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1 prepares carrier material FA-PEG-DSPE

[0027] Preparation of Folate-PEG-NH 2

[0028] Take 30.9mg (0.15mmol) DCC dissolved in 5ml dimethylsulfoxide (DMSO), add 300mgNH 2 -PEG-NH 2 , 66.2mg Folate, 10μl pyridine, stirred at 25°C for 24h, added 10ml of distilled water to terminate the reaction, centrifuged, took the supernatant, dialyzed with distilled water, and lyophilized. Use DEAE Sepharose FF ion-exchange column and Sephadex G-15 column in combination with AKTA explorer rapid purification system for separation and purification, and lyophilize to obtain yellow Folate-PEG-NH 2 Solid 154mg.

[0029] Preparation of Folate-PEG-SUC

[0030] Folate-PEG-NH 2 80.9mg was dissolved in 1ml DMF, SUC 23.8mg was dissolved in 1ml DMF, mixed, reacted at 50°C, and detected by spotting. After reacting for 4 hours, add 2ml of distilled water to stop the reaction, use SephadexG-15 column combined with AKTA explorer rapid purification system for separation and purific...

Embodiment 2

[0035] Embodiment 2 prepares carrier material MPEG-DSPE

[0036] Preparation of MeO-PEG-SUC

[0037] MeO-PEG-NH 2200mg was dissolved in 2ml DMF, SUC 80mg was dissolved in 1ml DMF, mixed, reacted at 50°C, and detected by spotting. After 4 hours of reaction, 2ml of distilled water was added to terminate the reaction, separated and purified by Sephadex G-15 column combined with AKTA explorer rapid purification system, and lyophilized to obtain 159.9 mg of white MeO-PEG-SUC solid.

[0038] Preparation of MeO-PEG-DSPE

[0039] Dissolve 90 mg of MeO-PEG-SUC in 1 ml of chloroform, 8 mg of DCC in 1 ml of chloroform, mix, and dissolve 254.4 mg of DSPE in 4 ml of chloroform, add to the above solution, react at 50 ° C, and detect the reaction by spotting. After 5 hours, the reaction was complete, and the chloroform was removed by rotary evaporation, and dried in vacuum overnight. Then add 50ml of ethanol, stir for 10min, centrifuge at 7500r / min for 20min, take the supernatant, repeat...

Embodiment 3

[0042] Example 3 Carrier Material Cytotoxicity Detection

[0043] Cervical cancer cells HeLa in the logarithmic growth phase were treated with 7.5×10 3 cells / well, inoculated in 96-well plate, 24h later, given 0.2-20uM micellar solution prepared by micelle carrier material FA-PEG-DSPE and MPEG-DSPE respectively, and incubated in 37°C incubator for 48h, Add 20 μl of 5 mg / ml MTT solution, incubate at 37°C for 4 hours, replace the culture solution with 200 μl DMSO, shake for 10 minutes, and measure the absorbance at 490 nm with a microplate reader.

[0044] The results showed that within the concentration range of 0.2-20uM, the cell survival rate of FA-PEG-DSPE was 93.47±3.402%-73.20±2.043%, and the cell survival rate of MPEG-DSPE was 96.21±7.261%-84.18±1.697%. The carrier material itself is less toxic to cells and has less influence on the next drug sensitivity test ( figure 2 ).

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Abstract

The invention belongs to the field of medicinal preparations and relates to a folate-mediated targeted polymeric micelle, in particular to the folate-mediated targeted polymeric micelle which entraps an insoluble anti-tumor medicament. The folate-mediated targeted polymeric micelle is prepared from two biocompatible materials, namely folate-polyethyleneglycol-phosphatidyl ethanolamine and methoxypolyethyleneglycol-phosphatidyl ethanolamine in a certain proportion, and entraps the insoluble anti-tumor medicament, so that the insoluble anti-tumor medicament is solubilized in the prepared polymeric micelle effectively. Experiments prove that the folate-mediated targeted polymeric micelle has the advantages of specifically targeting to inhibit the growth of tumor cells and effectively avoiding macrophage phagocytose and providing an ideal novel medicament carrier and preparation for the insoluble anti-tumor medicament.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a folic acid-mediated targeting polymer micelle, in particular to a folic acid-mediated targeting polymer micelle loaded with insoluble antitumor drugs. Background technique [0002] For the clinical treatment of tumor drugs, the biggest obstacle to the administration of insoluble anti-tumor drugs, especially injection administration, is the low solubility of the drug, which makes it difficult to prepare suitable preparations. Various methods to increase solubility are often required, such as preparing the drug Salt formation, adding co-solvent and surfactant solubilization, etc. Solubilization by surfactants is often the first choice due to the availability of relatively safe surfactants. For example, paclitaxel (paclitaxel, PCL) is a natural anticancer drug extracted from the trunk and bark of Taxus yew, and it is mainly used clinically for the treatment of ovarian can...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K47/48A61K47/34A61K31/337A61K31/4745A61K31/704A61P35/00A61K47/60
Inventor 陆伟跃韩雪刘婧刘敏谢操
Owner FUDAN UNIV
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