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Applications of temperature sensitive composite liposome in controlled release of water soluble and amphiphilic anti-cancer drugs

A compound lipid and plastid technology, applied in the field of biomedical materials, can solve the problems of insufficient therapeutic concentration, tumor resistance, slow drug release, etc., and achieve the effects of increasing local concentration, small side effects and low cost.

Inactive Publication Date: 2015-06-24
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the improved stability, complex liposomes can overcome the problem of toxic and side effects caused by traditional liposomes releasing drugs prematurely before reaching the target. However, some new problems may also arise: the release of drugs in the tumor area is too slow, Cannot reach the effective therapeutic concentration, leading to drug resistance of the tumor, etc.

Method used

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  • Applications of temperature sensitive composite liposome in controlled release of water soluble and amphiphilic anti-cancer drugs
  • Applications of temperature sensitive composite liposome in controlled release of water soluble and amphiphilic anti-cancer drugs
  • Applications of temperature sensitive composite liposome in controlled release of water soluble and amphiphilic anti-cancer drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Preparation of temperature-sensitive complex liposomes (the molar ratio of CFL:DPPC is 3:7)

[0050] (1) Materials and dosage: (100ml composite liposome dosage)

[0051] CFL: 31.5mg, DPPC: 70mg, MSPC: 7.36mg, DPPE-PEG2000: 16.75mg

[0052] (2) Preparation method:

[0053] According to the above, the various lipids were weighed, and complex liposome-forming lipids were first hydrolyzed in acidic ethanol solution. After incubation at 40 °C for 30 min, the chloroform solution containing DPPC, MSPC and DPPE-PEG2000 was added to the lipids hydrolyzed in the acidic solution and mixed uniformly. The solvent was then removed with a rotary evaporator, forming a thin film on the vial wall, which was further dried under vacuum overnight. Afterwards, 100 mL of ultrapure water was added to the vial and incubated in a water bath at 60 °C for 30 min. The mixture was vortexed for 20 min, followed by probe sonication for 5-10 min until a clear and transparent solution was obtained. ...

Embodiment 2

[0055] Preparation of temperature-sensitive complex liposomes (the molar ratio of CFL:DPPC is 4:6)

[0056] (1) Materials and dosage: (100ml composite liposome dosage)

[0057] CFL: 41.9mg, DPPC: 60mg, MSPC: 7.36mg, DPPE-PEG2000: 16.75mg

[0058] (2) Preparation method:

[0059] Weigh various phospholipids according to (1), and other operating steps are the same as in Example 1.

Embodiment 3

[0061] Preparation of temperature-sensitive complex liposomes (the molar ratio of CFL:DPPC is 5:5)

[0062] (1) Materials and dosage: (100ml composite liposome dosage)

[0063] CFL: 52.5mg, DPPC: 50mg, MSPC: 7.36mg, DPPE-PEG2000: 16.75mg

[0064] (2) Preparation method:

[0065] Weigh various phospholipids according to (1), and other operating steps are the same as in Example 1.

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Abstract

The invention discloses a composite liposome sensitive to high-intensity focused ultrasound (HIFU) and temperature, and applications thereof. The composite liposome is taken as a carrier used for drug intelligent controlled release under HIFU or heating. The composite liposome comprises at least one composite liposome forming lipid (CFL), at least one temperature-sensitive phospholipid, at least one lysophospholipid, and a lipid with covalently connected poly (ethylene glycol) (PEG). Temperature sensitive range of the composite liposome ranges from 39.0 to 45.0 DEG C; cyclicity is long; and the composite liposome is sensitive to HIFU. The invention also relates to applications of the HIFU and temperature sensitive composite liposome in controlled release of water soluble and amphiphilic anti-cancer drugs. The temperature sensitive composite liposome nanoparticle possesses excellent stability and biocompatibility, and excellent responsiveness capability on HIFU; under HIFU irradiation, the water soluble and amphiphilic anti-cancer drugs can be released out from the temperature sensitive composite liposome quickly; and curative effect is improved substantially.

Description

technical field [0001] The invention belongs to the field of biomedical materials, in particular to high-intensity focused ultrasound (HIFU) and temperature-sensitive composite liposomes and applications thereof. technical background [0002] Conventional chemotherapy drugs have the characteristics of short half-life and strong side effects. Therefore, the development of drug carriers has become an important branch of today's pharmacy. To achieve more accurate drug delivery, the controlled release performance of drug carriers is a necessary condition. An ideal drug controlled release technology should meet the following two conditions: (1) The drug carrier is stable in the blood circulation process, and will not cause drug leakage and premature release when the drug reaches the lesion; (2) It can be released rapidly at the lesion . The use of temperature-sensitive carriers offers the possibility to trigger rapid release of high concentrations of active drug in the target ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K41/00A61K47/34A61P35/00
Inventor 戴志飞梁晓龙蒋灵冬井立佳靳玉慎李小达
Owner PEKING UNIV
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