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Oxygen-carrying enhanced photodynamic photosensitive liposome and preparation and application thereof

A photosensitive lipid and photodynamic technology, applied in photodynamic therapy, liposome delivery, medical preparations of non-active ingredients, etc., can solve the problems of weakened tumor cell killing effect, tumor drug resistance, etc., and prolong the circulation time in the body , relieve alternating osmotic pressure, and avoid the effect of depolymerization

Inactive Publication Date: 2016-10-12
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The efficacy of these drugs depends on the oxygen environment of the cells. When the cells are partially hypoxic, their killing effect on tumor cells is weakened.
On the other hand, hypoxia leads to tumor drug resistance through the regulation of cell genome and proteome expression

Method used

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  • Oxygen-carrying enhanced photodynamic photosensitive liposome and preparation and application thereof
  • Oxygen-carrying enhanced photodynamic photosensitive liposome and preparation and application thereof
  • Oxygen-carrying enhanced photodynamic photosensitive liposome and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] A composition of the oxygen-carrying photodynamically enhanced photosensitive liposome provided by the present invention (see Table 1).

[0049] Table 1

[0050] prescription composition Prescription amount (mg) Doxorubicin Hydrochloride (DOX·HCI) 1.1 Yolk Lecithin (E80) 19.63 Cholesterol 5 Polyethylene glycol phospholipid (DSPE-PEG2000) 2.88 Indocyanine Green-Stearylamine (ICG-ODA) 2.69 Hemoglobin (Hb) 20

[0051] The prescribed amount of E80, Cholesterol, DSPE-PEG2000, and ICG-ODA was placed in an eggplant-shaped bottle, and an organic solvent was added to make it fully dissolved and mixed. Then, a water bath at 45°C reduced pressure and rotary evaporated overnight, and a uniform film was formed on the wall of the bottle. Add the mixed solution of oxygen-saturated Hb and doxorubicin hydrochloride into the eggplant-shaped bottle, fully hydrate, the film falls off and forms a multilayer liposome solution. Sonicate it ...

Embodiment 2

[0053] A composition of the oxygen-carrying photodynamically enhanced photosensitive liposome provided by the present invention (see Table 2).

[0054] Table 2

[0055] prescription composition Prescription amount (mg) Yolk Lecithin (E80) 24.25 Cholesterol 3.2 Polyethylene glycol phospholipid (DSPE-PEG2000) 2.16 Indocyanine Green-Stearylamine (ICG-ODA) 1.98 hemoglobin 15

[0056] The prescribed amount of E80, Cholesterol, DSPE-PEG2000, and ICG-ODA was placed in an eggplant-shaped bottle, and an organic solvent was added to make it fully dissolved and mixed. Then, the water bath was vacuum decompressed and rotary evaporated at 45°C overnight, and a uniform film was formed on the wall of the bottle. Add oxygen-saturated Hb solution to the eggplant-shaped bottle, fully hydrate, the film comes off and forms a multilayer liposome solution. Sonicate it to the desired particle size using probe sonication. The resulting lipid solution wa...

Embodiment 3

[0067] An application of the oxygen-carrying photodynamically enhanced photosensitive liposome provided by the present invention can carry oxygen components and improve tumor hypoxic microenvironment.

[0068] Three ICR mice were subcutaneously inoculated with 150 μL of ascites in the right axilla to obtain the S180 tumor-bearing mouse model. When the tumor volume is about 150mm 3 Randomly divided into normal saline group, lipo-ICG (liposomes carrying ICG) group and liposomes (liposomes carrying ICG-ODA and Hb) group in Example 2, respectively tail vein administration three times, 1 time / sky. After three administrations, the tumors were dissected for immunohistochemical staining. The result is as Figure 9 It was confirmed that the liposomes loaded with Hb can effectively reduce the expression of hypoxia-inducible factor HIF-1 in tumors, which shows that the liposomes in Example 2 can carry oxygen to tumors and relieve tumor hypoxia.

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Abstract

The invention provides a photosensitive liposome carrying oxygen to enhance photodynamics, which is composed of phospholipids, cholesterol, long-circulation materials, hemoglobin, and chemotherapeutic drugs and / or photosensitizers, each component is dissolved in an organic solvent, and the Steam to form a thin film, then add oxyhemoglobin solution, or a mixed solution of photosensitizers and / or chemotherapeutic drugs and oxyhemoglobin, and hydrate to obtain a multilayer liposome solution, which is obtained by ultrasonication and purification. The liposome of the present invention can simultaneously carry oxygen, chemotherapeutic drugs and / or photosensitizers to the tumor site, alleviate the hypoxic state of tumor cells, improve the sensitivity of tumor cells to chemotherapeutic drugs, inhibit tumor growth and metastasis, and can also Under the irradiation of near-infrared light, the photosensitizer in the liposome generates more singlet oxygen, resulting in an enhanced photodynamic therapy effect. The loaded drug molecules are released to realize remote control of drug release.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a novel liposome drug delivery system for delivering oxygen molecules and drug molecules to tumor sites, in particular to a photosensitive liposome carrying oxygen and enhancing photodynamic force, as well as its preparation and application. Background technique [0002] As early as 1955, Thmolison et al. proposed tumor hypoxia for the first time in their research. After more than 60 years of clinical and experimental confirmation, hypoxia widely exists in cervical cancer, breast cancer, vaginal cancer, head and neck cancer, prostate cancer, and rectal cancer. , lung cancer, brain tumors, soft tissue sarcomas and other tumors. And the study found that the volume greater than 1cm 3 hypoxia in tumors. In the tumor tissue, the uncontrolled growth and proliferation of tumor cells consume a large amount of nutrients and oxygen, and the new blood vessel network cannot be established in a timely...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/26A61K47/28A61K38/42A61K45/06A61K41/00A61P35/00A61K31/704A61K31/337A61K31/4745A61K31/475A61K31/282
CPCA61K9/127A61K31/282A61K31/337A61K31/4745A61K31/475A61K31/704A61K38/42A61K41/0057A61K41/0071A61K45/06A61K47/26A61K47/28
Inventor 游剑曲佳鑫
Owner ZHEJIANG UNIV
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