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Long circulation liposome with modified integrin and carried anticancer medicine for injection

A long-circulating liposome and liposome technology, which is applied in the directions of liposome delivery, anti-tumor drugs, medical preparations of inactive ingredients, etc. less antigenic effect

Inactive Publication Date: 2006-10-18
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some foreign scholars use folic acid, transferrin and monoclonal antibodies to modify recessive liposomes to increase the targeting of drug delivery. Animal experiments have proved that they can significantly improve the efficacy of anticancer drugs, but there is no such product on the market.

Method used

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  • Long circulation liposome with modified integrin and carried anticancer medicine for injection
  • Long circulation liposome with modified integrin and carried anticancer medicine for injection
  • Long circulation liposome with modified integrin and carried anticancer medicine for injection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1, RGD-modified long-circulation liposomes loaded with doxorubicin

[0028] Take soybean lecithin, cholesterol, DSPE-PEG2000 and DSPE-PEG-RGD (molar ratio is 20:10:2:1), put them in a round bottom flask, add an appropriate amount of chloroform to dissolve, heat in a water bath and vacuum rotary evaporation to remove the organic solvent , so that a phospholipid film is formed on the wall of the flask, add 123mM ammonium sulfate solution, and sonicate in a water bath until blue opalescence appears. A polycarbonate film of 200 nm was extruded 5 times. Pass the prepared liposomes through a SephadexG50 column, elute with PBS buffer (pH7.4) as the mobile phase, collect the liposome fraction, heat the collected liposomes in a water bath at 40°C, and add doxorubicin Incubate the powder for 20 minutes and shake it frequently to obtain this product. The particle diameter of above-mentioned obtained doxorubicin liposome should be controlled at about 120nm.

Embodiment 2

[0029] Example 2, long-circulating liposomes modified by RGD analogs (RGDm) loaded with doxorubicin

[0030] Take soybean lecithin, cholesterol, DSPE-PEG2000 and DSPE-PEG-RGDm (the molar ratio is 20:10:2:1), put them in a round-bottomed flask, add an appropriate amount of chloroform to dissolve, heat in a water bath, and vacuum rotary evaporation to remove the organic solvent , so that a phospholipid film is formed on the wall of the flask, add 123mM ammonium sulfate solution, and sonicate in a water bath until blue opalescence appears. A polycarbonate film of 200 nm was extruded 5 times. Pass the prepared liposomes through a Sephadex G50 column, elute with PBS buffer (pH7.4) as the mobile phase, collect the liposome fraction, heat the collected liposomes in a water bath at 40°C, add Adriamycin Incubate the plain powder for 20 minutes and shake it frequently to obtain this product. The particle diameter of above-mentioned obtained doxorubicin liposome should be controlled at...

Embodiment 3

[0031] Example 3, long-circulating liposomes modified by RGD and analogues loaded with doxorubicin

[0032] Take soybean lecithin, cholesterol, DSPE-PEG2000 (molar ratio is 20:10:2), put them in a round bottom flask, add an appropriate amount of chloroform to dissolve, put in a water bath and heat in a vacuum rotary evaporation to remove the organic solvent, so that phospholipids are formed on the wall of the flask Add 123mM ammonium sulfate solution to the thin film, and sonicate in a water bath until blue opalescence appears. A polycarbonate film of 200 nm was extruded 5 times. Pass the prepared liposomes through a Sephadex G50 column, use PBS buffer (pH7.4) as the mobile phase to elute, collect the liposomes, and place the collected liposomes at 40°C Heat in a water bath, add doxorubicin powder and incubate for 20 minutes, and shake from time to time. Then add the prescribed amount of guiding compound DSPE-PEG-RGD or DSPE-PEG-RGDm and continue to incubate for 30 minutes, ...

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Abstract

The present invention relates to integrin ligand modified long circulation liposome carrying anticarcinogen for injection, and is especially one kind of injected anticarcinogen carrying targeting liposome administration system. The efficient administration system is obtained through modifying the surface of liposome simultaneously with both polyethylene glycol and integrin containing arginine-glycine-asparagic acid sequence or RGD analogue.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a targeted liposome drug delivery system loaded with anticancer drugs for injection. The system uses polyethylene glycol (PEG) and A high-efficiency liposome drug delivery system obtained by modifying integrin ligands containing arginine-glycine-aspartic acid sequence (RGD) or RGD analogues. Background technique [0002] Malignant tumors have always been an important disease that plagues human beings, and there is currently no cure for cancer. The traditional therapy for malignant solid tumors is surgical resection of the tumor followed by chemotherapy with antineoplastic drugs. Most chemotherapeutic drugs are non-selective, and these drugs also have a killing effect on normal cells while killing tumor cells, so they will produce serious side effects, such as the cardiotoxic effect of doxorubicin. Encapsulating anticancer drugs with liposomes can significant...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K45/00A61K47/18A61K47/42A61P35/00
Inventor 张强熊小兵王坚成张华
Owner PEKING UNIV
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