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A Thermosensitive Liposome Released by Magnetothermal Release

A technology of heat-sensitive liposomes and liposomes, applied in liposome delivery, preparations for in vivo tests, medical preparations of non-active ingredients, etc., can solve the problems of poor precision of application methods and achieve selectivity high effect

Active Publication Date: 2020-09-22
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] The purpose of the present invention is to target thermosensitive liposomes after they are located in the target treatment tissue area, and there is no method for verification and characterization confirmation before releasing the drug, which leads to the problem of poor accuracy of the application means in the release process of the targeted drug, and provides a method that can characterize Near-infrared luminescent thermosensitive liposomes targeting drug delivery sites

Method used

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  • A Thermosensitive Liposome Released by Magnetothermal Release
  • A Thermosensitive Liposome Released by Magnetothermal Release
  • A Thermosensitive Liposome Released by Magnetothermal Release

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 101

[0091] DPPC is used as the basic material, and DSPG is used as the auxiliary material.

[0092] Add 750 mg of DPPC and 75 mg of DSPG to 20 mL of a mixed solution of chloroform and methanol (volume ratio of chloroform and methanol = 4:1), heat to 55 ° C, stir for 20 minutes until completely dissolved, and evaporate to dryness for 4 hours. The organic solvent is completely removed. Add 18 mL of phosphate buffer (pH=7.4±0.1), sonicate for 15 minutes, and then freeze-dry to obtain liposome microspheres.

[0093] Due to the limited tolerance of the human body to temperature, the basic material of TSL should be selected as a phospholipid with a lower phase transition temperature. Selected in this embodiment: DPPC, dipalmitoylphosphatidylcholine, phase transition temperature is 41 ℃. DSPG, distearoylphosphatidylglycerol, has a phase transition temperature of 55°C. DSPG is introduced because the drugs introduced later have little effect on the phase transition behavior of DSPG and ...

Embodiment 102

[0095] Thin film dispersion method

[0096] Weigh 500mg of DPPG, 200mg of DPSP, and 100mg of DSPC (55°C) in a rotary evaporator, add 30mL of chloroform, heat to 58°C, and evaporate completely on a rotary evaporator to remove chloroform. Forms a uniform film layer on the bottle wall. In addition, weigh 20mg RGD and add it into 15mL of phosphate buffer solution with pH=7.4, fully dissolve it, then add it into the aforementioned rotary steamer, mix well, stir for 10 minutes for hydration, and ultrasonic for 30 minutes to obtain milky white liposomes suspension. It is a heat-sensitive liposome material, which is freeze-dried to obtain a dry liposome material.

[0097] The selected DPPG (Tm=41°C), DPSP (Tm=41°C), DSPC (Tm=55°C), and several liposome raw materials are mixed together, and the phase transition temperature of the liposome shell after synergy is slightly higher than At 41°C, the stability of the encapsulated drug is higher, and the temperature of phase change relea...

Embodiment 103

[0099] freeze drying

[0100] Weigh 15 mg doxorubicin and dissolve it in an appropriate amount of phosphate buffer solution with pH=6.8, and sonicate for 15 minutes to obtain a doxorubicin solution. Then weigh a certain amount of DPPC 500mg and PSPC 500mg, add them to 30mL of anhydrous ether, stir magnetically for 10min, add the above-mentioned doxorubicin solution, homogenize at a high speed of 15000r / min for 5min, evaporate under reduced pressure at room temperature for 15 minutes, add 10mg of manna Alcohol, ultrasonic 20min, obtain emulsion, filter with 0.22 μm microporous membrane, filtrate freeze-dry with lyophilizer, obtain the liposome that wraps doxorubicin.

[0101] The selected PSPC (Tm=44°C), and the Tm of the liposomes prepared with DPPC are between 41 and 44°C, the phase transition temperature is suitable, and it can be used in a wide range of situations. The liposome obtained by freeze-drying is anhydrous dry liposome, and the liposome structure and function a...

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Abstract

The invention discloses a thermosensitive liposome capable of conducting magnetic-heat release. The thermosensitive liposome consists of a phospholipid liposome which is constructed by a thermosensitive material and magnetic nanoparticles covered in the phospholipid liposome, wherein phase-transition temperature of the phospholipid liposome is at 40-51 DEG C; the magnetic nanoparticles are superparamagnetic ferriferrous oxide particles; the magnetic nanoparticles can become heated in a (high-frequency) alternating magnetic field, and the phospholipid liposome is heated up to the phase-transition temperature and substances in the phospholipid liposome are released; and near-infrared fluorescence quantum dots are also covered in the phospholipid liposome. The thermosensitive liposome provided by the invention, in which the magnetic nanoparticles are covered, has a magnetic-heat effect, and the thermosensitive liposome can achieve local heating to result in structural damage in the alternating magnetic field, so that effective ingredients in the thermosensitive liposome are released; the thermosensitive liposome has the characteristic of being high in controlled-release precision; and in the combination with the near-infrared fluorescence quantum dots which serve as a tracing ingredient, the problem that the magnetic thermosensitive liposome, when entering a body, is difficult to represent is effectively solved, and a tracing effect is achieved.

Description

technical field [0001] The invention relates to a heat-sensitive liposome, in particular to a heat-sensitive liposome with magnetocaloric properties, capable of generating heat under an alternating magnetic field to release components in the heat-sensitive liposome. Background technique [0002] Drugs in modern medicine usually refer to substances that have certain physiological and biochemical effects on the body and have certain effects in disease diagnosis, prevention or treatment. The therapeutic effect of drugs is divided into cause-based treatment and symptomatic treatment. Cause-based treatment means that the role of drugs is to eliminate the primary pathogenic factor of the disease, which is often said in traditional Chinese medicine to cure the root cause. Symptomatic treatment means that the role of drugs is to improve the disease. Symptoms, that is, the symptoms that Chinese medicine often says. Whether it is a palliative or a permanent cure, drug molecules must ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K9/127A61K47/69A61K49/00A61K31/704A61P35/00
CPCA61K9/1271A61K31/704A61K41/00A61K41/0028A61K49/0067
Inventor 赵强李珍珍潘玉瑾黄华莹
Owner SICHUAN UNIV
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