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Composite nano-liposome and application thereof

A technology of nano-liposomes and mixtures, which is applied in liposome delivery, drug combination, medical preparations of non-active ingredients, etc. It can solve the problems of limited application effect, tumor hypoxia, low absorption rate, etc., and achieve tumor relief Hypoxia, enhanced long-circulation effect, uniform distribution effect

Active Publication Date: 2019-10-08
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, such compounds often have disadvantages such as poor water solubility, low absorption rate, low accumulation in the lesion, and hypoxia inside the tumor, which limit their application effect.

Method used

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  • Composite nano-liposome and application thereof
  • Composite nano-liposome and application thereof
  • Composite nano-liposome and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Preparation of liposome product Ⅰ

[0048] (1) Precisely weigh 80 mg of soybean lecithin, 10 mg of FA-DSPE-mPEG2k and 10 mg of cholesterol in a 100 ml round bottom flask, and dissolve them in 20 ml of chloroform under nitrogen protection until they are completely dissolved. Evaporate under pressure to form a film, put it in a vacuum oven and dry at 37°C overnight. Add 20ml of PBS and stir with a magnetic stirrer (660 rpm) until completely dissolved. Put it into a -80°C refrigerator, freeze and thaw repeatedly 3 times to obtain solution A.

[0049] (2) Homogenize the solution A with a high-pressure homogenizer, the voltage is 40mV, the pressure is 800bar, the temperature of the water bath is 65°C, and the cycle is 30 times. The obtained solution was sequentially passed through 0.4 μm and 0.2 μm polycarbonate membranes through an extruder in a water bath at 65° C., each repeated 10 times to obtain solution B.

[0050] (3) Take 9.9 ml of the solution B obtained in (2), ...

Embodiment 2

[0072] Preparation of liposome product Ⅰ

[0073](1) Precisely weigh 80 mg of soybean lecithin, 10 mg of FA-DSPE-mPEG2k, 10 mg of cholesterol, and 1 mg of photosensitizer Cy5-Br in a 100 ml round bottom flask, and dissolve it in 20 ml of chloroform under nitrogen protection until it is completely dissolved. Evaporate under reduced pressure on a rotary evaporator to form a film, and put it in a vacuum oven to dry at 37°C overnight. Add 20ml of PBS and stir with a magnetic stirrer (660 rpm) until completely dissolved. Put it into a -80°C refrigerator, freeze and thaw repeatedly 3 times to obtain solution A.

[0074] (2) Homogenize the solution A with a high-pressure homogenizer, the voltage is 40mV, the pressure is 800bar, the temperature of the water bath is 65°C, and the cycle is 30 times. The resulting solution was sequentially passed through 0.4 μm and 0.2 μm polycarbonate membranes through an extruder in a water bath at 65° C., each repeated 10 times, to obtain I: liposom...

Embodiment 3

[0082] The liposomes prepared in Example 1 were tested for comparative performance.

[0083] (1) Performance test experiment 1: Morphology analysis of liposome product FA-L@MD@CAT

[0084] The liposome solution FA-L@MD@CAT was taken, and the hydrated average particle size measured by a Zeta potential and particle size analyzer (Malvern Zetasizer, Nanozs90) was 122.4nm, and the polydispersity index (Poly Diversity Index, "PDI") was 0.129, the zeta potential value is -28mV. The particle size distribution is shown in figure 1 Shown in (b). Obtain the TEM image of liposome solution FA-L@MD@CAT by transmission electron microscope (TEM, HT7700EXALENS), such as figure 1 Shown in (a).

[0085] (2) Performance test experiment 2: Using a microplate reader to measure cytotoxicity in vitro

[0086] To assess in vitro cytotoxicity, MCF7 cells were incubated in a 96-well plate until the cell density reached 1 × 10 per well. 4 When 1 cell, add different concentrations of L@D, L@M, L@MD...

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Abstract

The invention provides a composite nano-liposome and application thereof. The composite nano-liposome is prepared from soybean lecithin, folic acid-modified distearoyl phosphoethanolamine-polyethyleneglycol 2000, cholesterol, a photosensitizer, chemotherapeutic drugs and catalase. A system utilizes the liposome as a nano drug carrier system, the solubility of the drugs is improved, the toxic andside effects are reduced, and the targeting ability to a tumor site is increased. According to the composite nano-liposome, the photosensitizer and an anticancer drug are encapsulated together, and itis found that the two drugs have a good synergistic therapeutic effect through cell and in-vivo antitumor experiments; in addition, the catalase is loaded to alleviate tumor hypoxia caused by the photodynamic therapy, and the inhibition to tumors is enhanced; and folic acid-modified phospholipids are used for realizing active targeting of the tumors, and the anti-tumor effect is greatly enhanced.

Description

technical field [0001] The invention relates to a liposome preparation method, chemotherapy and photodynamic synergistic therapy, in particular to the preparation and application of a nano-liposome with multi-mechanism synergistic anti-tumor activity. [0002] technical background [0003] Cancer is still a difficult problem in the world. Chemotherapy and radiotherapy are currently one of the main clinical treatment methods for cancer. Chemotherapy, as a traditional treatment method, is still widely used in clinical cancer treatment, and doxorubicin is a commonly used chemotherapeutic drug in clinic, but due to the poor enrichment ability of doxorubicin in tumor sites and serious toxic side effects on the heart Disadvantages such as easy to produce drug resistance limit the effect of treatment. [0004] Photodynamic therapy (Photodynamic Therapy, PDT), as one of the emerging means of cancer treatment, can effectively inhibit tumors. BODIPY and cyanine dye photosensitizers h...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/24A61K47/28A61K41/00A61K31/704A61K31/337A61P35/00
CPCA61K9/127A61K31/337A61K31/704A61K41/0057A61K47/24A61K47/28A61P35/00A61K2300/00
Inventor 彭孝军史超樊江莉李明乐黄海桥
Owner DALIAN UNIV OF TECH
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