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Thermo-sensitive liposome as well as preparation method and application thereof

A heat-sensitive liposome and phospholipid technology, applied in the field of medicine, can solve the problems of large particle size, biological toxicity, poor biocompatibility, etc., and achieve increased fluidity and permeability, improved therapeutic effect, biological good compatibility

Active Publication Date: 2014-07-09
珠海中科先进技术研究院有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] (1) The distribution of thermosensitive liposomes in the body and the enrichment status at the target site are unclear, and it is difficult to control the heating time of the target site, resulting in poor therapeutic effect of thermosensitive liposomes; (2) due to carbon nano Tubes, etc. are insoluble in water and organic solvents, and are easy to aggregate into bundles in the solution. The particle size of the prepared thermosensitive liposomes is generally 100-200nm, which is relatively large, and the particle size uniformity is not good, which is not conducive to Drugs are treated efficiently by enhancing the osmotic retention effect (EPR effect); (3) Materials such as carbon nanotubes, graphene, and nano-gold have poor biocompatibility and have certain toxic effects on organisms

Method used

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  • Thermo-sensitive liposome as well as preparation method and application thereof
  • Thermo-sensitive liposome as well as preparation method and application thereof
  • Thermo-sensitive liposome as well as preparation method and application thereof

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preparation example Construction

[0055] In a second aspect, the present invention provides a method for preparing thermosensitive liposomes, comprising the following steps:

[0056] (1) dissolving phosphatidylcholine and polyethylene glycol derivatized phospholipids at a mass ratio of 25-35:1-5, and after rotary evaporation to obtain a phospholipid film, and then dissolving the phospholipid film to obtain a phospholipid solution;

[0057] (2) Dissolving the photosensitizer and chemotherapeutic drug at a mass ratio of 1 to 4:1 is added dropwise to the phospholipid solution and ultrasonicated for 5 to 10 minutes, followed by ultrafiltration for 3 to 5 times to obtain the thermosensitive lipid Plastids, the thermosensitive liposomes include chemotherapeutic drugs, photosensitizers, phosphatidylcholine and polyethylene glycol derivatized phospholipids, the photosensitizers are indocyanine green or chlorin e6, the thermosensitive The particle size of the liposome is 40-60 nm.

[0058] The phosphatidylcholine and ...

Embodiment 1

[0083] A preparation method of thermosensitive liposomes, comprising the following steps:

[0084] (1) 2.7mg of DSPC (purchased from Sigma-Aldrich), 1.5mg of DMPC (purchased from Sigma-Aldrich), 0.15mg of cholesterol (purchased from Avanti) and 0.15mg DSPE-PEG-MAL (purchased from (from Avanti company) was dissolved in 4mL ethanol aqueous solution with a volume fraction of 4%; then the ethanol solution was evaporated to dryness using a rotary evaporator, and a uniform phospholipid film was formed in a 50mL round-bottomed flask; 3ml ultrapure water was added to dissolve the phospholipid film, Form a phospholipid solution;

[0085] (2) Dissolve 0.15mg of DOX and 0.6mg of ICG (both purchased from Sigma-Aldrich) in 0.15mL of ultrapure water, mix well and add dropwise to the phospholipid solution in the round bottom flask, during which cell ultrasound is used Ultrasound at a frequency of 20 kHz and a power of 130 W for 5 minutes with a crushing instrument; finally, centrifuge and u...

Embodiment 2

[0096] A preparation method of thermosensitive liposomes, comprising the following steps:

[0097] (1) 2.7mg of DSPC (purchased from Sigma-Aldrich), 1.5mg of DMPC (purchased from Sigma-Aldrich), 0.45mg of cholesterol and 0.75mg DSPE-PEG-MAL (purchased from Sigma-Aldrich) Dissolve in 4mL ethanol solution with a volume fraction of 4%; then use a rotary evaporator to evaporate the ethanol solution to dryness, and form a uniform phospholipid film in a 50mL round bottom flask; then add 3ml ultrapure water to dissolve the phospholipid film to form a phospholipid solution;

[0098] (3) Dissolve 0.15mg of DOX and 0.15mg of ICG in 0.15mL of ultrapure water and mix them evenly, then add dropwise to the phospholipid solution in the round bottom flask. Ultrasonic at the highest power for 5 minutes; finally use a 10kDa ultrafiltration tube to centrifuge and ultrafilter three times to obtain thermosensitive liposomes (expressed as DI-NPs).

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Abstract

The invention provides thermo-sensitive liposome. The thermo-sensitive liposome comprises a chemotherapeutic drug, a photosensitizer, phosphatidylcholine and polyethylene glycol-derived phospholipid, wherein the photosensitizer is indocyanine green or chlorins e6; the grain size of the thermo-sensitive liposome is 40-60 nm; by virtue of living-body fluorescence imaging, a distribution process of the thermo-sensitive liposome can be observed in real time; under a near-infrared light irradiation condition, the chemotherapeutic drug can be quickly and effectively released, so that the chemotherapeutic drug can be enriched at a target part very well; the obtained thermo-sensitive liposome particle has smaller particle diameter less than 100 nm, and good biocompatibility. The preparation method of the thermo-sensitive liposome is simple and easy to operate.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to a thermosensitive liposome and its preparation method and application. Background technique [0002] Thermosensitive liposome is a new dosage form of drug delivery system. At normal body temperature, it is difficult for the drug to diffuse out through the liposome membrane, and when the heat-sensitive liposome passes through the heated target site with the blood circulation, the local high temperature can promote the release of the drug at the target site and form a higher At present, the photosensitizers in thermosensitive liposomes are generally single-walled or multi-walled carbon nanotubes, graphene, nano gold and other materials, but these thermosensitive liposomes have the following problems: [0003] (1) The distribution of thermosensitive liposomes in the body and the enrichment status at the target site are unclear, and it is difficult to control the heating time of th...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K41/00A61K33/24A61K31/337A61K31/704A61K31/475A61K47/24A61K47/34A61P35/00
Inventor 蔡林涛赵鹏飞郑明彬罗震宇龚萍郑翠芳岳彩霞
Owner 珠海中科先进技术研究院有限公司
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