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Sorafenib solid lipid nanoparticles as well as preparation method and application thereof

A sorafenib lipid and a technology for describing sorafenib lipid, which are applied in the field of sorafenib lipid nanoparticles and their preparation, and can solve the problem of affecting the drug efficiency of sorafenib, not proposed, and not found. Patients with advanced hepatocellular carcinoma, etc., to achieve the effect of enhancing photostability and tumor aggregation, improving toxicity and solubility, and improving blood circulation time

Inactive Publication Date: 2018-12-28
HUBEI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Sorafenib is the first choice for patients with advanced cellular liver cancer. Patients have to face the defects of Sorafenib while receiving Sorafenib treatment. First, the solubility of Sorafenib is extremely Poor, the solubility in water is not more than 10μg / mL, which greatly affects the drug efficiency of patients taking sorafenib
Second, Sorafenib is very cytotoxic, and patients receiving Sorafenib have to endure side effects including diarrhea, dysentery, weight loss, high blood pressure, anorexia, voice change, nausea and vomiting, etc.
Third, as sorafenib is a small-molecule targeted drug, tumor cells are prone to strong resistance to it, which leads to no significant reduction in tumor volume after patients receive sorafenib treatment , and only extended patients' life expectancy by an average of three months compared to placebo treatment
Although sorafenib has so many shortcomings, so far, there is still no drug that can replace sorafenib for systemic treatment and prolonging the life of patients with advanced hepatocellular carcinoma. At the same time, there is no way to improve the shortcomings of Sorafenib clinically.

Method used

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  • Sorafenib solid lipid nanoparticles as well as preparation method and application thereof
  • Sorafenib solid lipid nanoparticles as well as preparation method and application thereof
  • Sorafenib solid lipid nanoparticles as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] 1. Preparation of Sorafenib Lipid Nanoparticles (SILS for short)

[0035] 1. Prepare phospholipid by mixing dipalmitoylphosphatidylcholine DPPC, cholesterol and DSPE-PEG2000.

[0036] 2. Weigh Sorafenib (SF) and phospholipids, add methanol and chloroform (volume ratio 2:1) and shake to dissolve, obtain the organic phase and remove the organic phase by rotary evaporation with a rotary evaporator to obtain phospholipids containing Sorafenib film.

[0037]3. Weigh indocyanine green (ICG), add it into the water for injection, and dissolve to obtain the water phase.

[0038] 4. Keep the temperature at 60°C, add the water phase into the phospholipid film, and stir the mixture with a magnetic stirrer at 320 rpm for 4 hours. Sonicate the prepared liposomes for 20 minutes, extrude once with a 450nm filter membrane, and then repeatedly extrude 5 times through a 200nm and 100nm filter membrane with a liposome extruder, and store at 4°C.

[0039] Simultaneously prepare blank lip...

experiment example 1

[0043] Experimental Example 1 Sorafenib Lipid Nanoparticle Performance Detection

[0044] 1. The morphology of SILS was observed by negative staining method of transmission electron microscope. Such as figure 1 Shown, is the transmission electron microscope figure of this Sorafenib lipid nanoparticle (abbreviation SILS); Transmission electron microscope (TEM) figure has shown clear typical spherical lipid shape, has further confirmed that SILS is stable in water, to The aggregation and fusion of vesicles have a certain inhibitory effect.

[0045] 2. The particle size, polyhedral index (PDI) and Zeta potential of SILS were further determined by ZetaSizer Nano series nanometer instrument Co., Ltd. Such as figure 2 Shown is the diameter and the polydispersity index (PDI) figure of this Sorafenib lipid nanoparticle; And summarize the following table 1.

[0046] Table 1

[0047] sample

Size (nm)

PDI

Zeta potential

SILS

143.4±3.9

0.123±0.008 ...

experiment example 2

[0051] Experimental Example 2 Photothermal Effect of Sorafenib Lipid Nanoparticles

[0052] 1. In order to clarify the photothermal effect of SILS (60μg / mL ICG), we analyzed the near-infrared (808nm, 2W / cm 2 ) temperature rise characteristics of free SF, free ICG and SILS under irradiation, such as Figure 6 shown.

[0053] 2. Thermal image ( Figure 7 ) showed that the maximum temperatures of SILS and free ICG were 65.5°C and 58.9°C, respectively. The increase in the maximum temperature of SILS relative to free ICG may be due to the increased stability and absorbance of ICG by liposomes. Therefore, encapsulated ICG is more effective at increasing temperature than free ICG.

[0054] 3. We also explored the photostability of SILS and free ICG (60μg / mL ICG). First, SILS and free ICG were irradiated with 808nm near-infrared laser (2.0W / cm 2 ) for 3 minutes and then cooled to room temperature. Without near-infrared laser irradiation for 10 min. Typical temperatures in the ...

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Abstract

The invention provides sorafenib solid lipid nanoparticles and a preparation method thereof. A phospholipid film is used as a shell, sorafenib and indocyanine green are taken as cores, wherein liposoluble sorafenib is encapsulated in a hydrophobic region of the phospholipid bilayer, and hydrophilic indocyanine green is located in liposome vesicles formed by the phospholipid bilayer. The preparation method comprises the following steps: weighing sorafenib and phospholipid, adding an organic solvent for dissolution to obtain an organic phase, and then removing an organic solvent to obtain the phospholipid film containing sorafenib; weighing indocyanine green, and dissolving indocyanine green in deionized water to obtain a water phase; adding the obtained water phase to the obtained phospholipid film, stirring and mixing the solution uniformly, and performing squeezing and filtering to obtain the final product. According to the sorafenib solid lipid nanoparticles, sorafenib and indocyanine green are loaded into a phospholipid film nano carrier together, so that toxicity and solubility of sorafenib can be improved, and light resistance and tumor aggregation resistance of indocyanine green can be enhanced.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a lipid nanoparticle of sorafenib and its preparation method and application. Background technique [0002] As of 2017, Sorafenib is the only drug approved by the US Food and Drug Administration to prolong the life of patients with advanced cellular liver cancer. Sorafenib is a polyprotein with a biaryl structure Kinase inhibitors, on the one hand, can target the two subtypes of Raf1 and BRaf in the Raf family in the downstream Raf / serine (serine) / threonine (threonine) kinase of Ras, and Ras is a mitogen-activated protein kinase ( mitogen-activated proteinkinase) signaling pathway is a key molecule that regulates the activity of the Raf / Mek / Erk pathway. After phosphorylation, these kinases can finally promote cell proliferation by up-regulating a series of genes related to cell proliferation. Sorafenib can target Raf Two subtypes in the family to inhibit the proliferation of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K9/127A61K9/51A61K31/44A61K47/24A61K47/22A61P1/16A61P35/00
CPCA61K9/127A61K9/5123A61K31/44A61K41/0052A61P1/16A61P35/00A61K2300/00
Inventor 徐祖顺贺乾元杨盛力
Owner HUBEI UNIV
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