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SPIO labeled pH sensitive drug-carrying liposome and preparation method thereof

A sensitive, drug-lipid technology, applied in the field of pH-sensitive drug-loaded liposomes traced by SPIO and its preparation, can solve the problems of inability to perform real-time, short half-life, and inability to detect changes in drug concentration, and achieve good superparamagnetic properties, Simple preparation method and good wrapping effect

Active Publication Date: 2018-09-18
重庆市人民医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above three methods for confirming targeting have obvious disadvantages, such as the detection of drug concentration in living tissue, which cannot be carried out in real time, and cannot detect the dynamic drug concentration changes in each living body; the fluorescent agent is mainly used as a contrast agent to develop in vitro cells or isolated tissues ; 99mTc has obvious radioactivity and short half-life (6.02h)

Method used

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  • SPIO labeled pH sensitive drug-carrying liposome and preparation method thereof
  • SPIO labeled pH sensitive drug-carrying liposome and preparation method thereof
  • SPIO labeled pH sensitive drug-carrying liposome and preparation method thereof

Examples

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Effect test

Embodiment 1

[0029] Example 1: A SPIO-traceable pH-sensitive drug-loaded liposome was obtained using the following mass ratio: 2.5 parts of misonidazole, 30 parts of phosphatidylethanolamine, 10 parts of cholesterol, 10 parts of linoleic acid, carboxymethyl 0.5 parts of chitosan, 0.5 parts of superparamagnetic iron oxide nanoparticles, and 2 parts of vitamin E. The accumulative release of misonidazole pH-sensitive liposomes traced by SPIO under different pH conditions is as shown in the attached drawing of the description figure 1 As shown, the accumulative release of the misonidazole pH-sensitive liposomes traced by SPIO under different pH conditions is shown in the accompanying drawing of the description figure 2 As shown, the misonidazole pH-sensitive liposome particle size distribution diagram traced by SPIO is shown in the accompanying drawing image 3 As shown, the misonidazole pH-sensitive liposome potential map traced by SPIO is shown in the accompanying drawing Figure 4 As sho...

Embodiment 2

[0037] A SPIO traced pH-sensitive liposome and a preparation method thereof, comprising the following steps:

[0038] A1: Take 5 parts of paclitaxel, 30 parts of phosphatidylethanolamine, 10 parts of cholesterol and 10 parts of linoleic acid in a flask, then add chloroform to dissolve, connect the flask to a rotary evaporator, and reduce Under the condition of high pressure, the chloroform was evaporated to dryness, and a film was formed on the inner wall of the beaker;

[0039] A2: Add an aqueous solution containing 0.5 parts of SPIO into the beaker, hydrate with a rotary evaporator at 50±1°C, 100r / min, and protect from light for 60 minutes to obtain a liposome solution;

[0040] A3: Use high-speed centrifugation to remove paclitaxel and SPIO not encapsulated in liposomes to obtain a liposome suspension;

[0041] A4: Add 0.5 parts of carboxymethyl chitosan solution with a mass percentage of 0.3% to the liposomes, and perform hydration for 30 minutes to obtain SPIO-traceable ...

Embodiment 3

[0044] A SPIO traced pH-sensitive liposome and a preparation method thereof, comprising the following steps:

[0045] B1: Take 30 parts of phosphatidylethanolamine, 10 parts of cholesterol and 10 parts of linoleic acid in a flask, add dimethyl sulfoxide and mix it as phase A, mix pure water, glycerin, 5 parts of cisplatin and 0.5 part of SPIO as B Phase, mix Phase A and Phase B, pour into a blender, stir at 55°C for 3 minutes, then take it out and put it into an emulsifier for emulsification for 30 seconds, and then put it into a high-pressure emulsifier for emulsification 4 times;

[0046] B2: put the product emulsified in the high-pressure emulsifier in step B1 into an ultrasonic oscillator for defoaming, and then add PBS buffer solution with a pH of 7.4 to form a liposome suspension;

[0047] B3: Use high-speed centrifugation to remove cisplatin and SPIO not encapsulated in liposomes to obtain a liposome suspension; perform ultrasonication on the liposome suspension, and pa...

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Abstract

The invention discloses an SPIO labeled pH sensitive drug-carrying liposome which is prepared from the following components in parts by mass: 1-10 parts of bulk drugs, 1-50 parts of phosphatidyl ethanolamine, 1-30 parts of cholesterol, 1-30 parts of linoleic acid, 0-10 parts of carboxymethyl chitosan, and 0-10 parts of superparamagnetic iron oxide nanoparticles. The invention further discloses a preparation method of the SPIO labeled pH sensitive drug-carrying liposome. The preparation method comprises the following steps: S1, placing phosphatidyl ethanolamine, cholesterol and linoleic acid ina flask, adding chloroform for dissolving, adding a water soluble drug solution for ultrasonic treatment to form a W / O emulsion; S2, evaporating to a gel state under the pressure reduction condition;adding a buffering solution, and continuously evaporating to form an aqueous suspension; S3, adding the superparamagnetic iron oxide nanoparticles and performing freeze thawing on a liposome suspension for three times; and centrifugally removing the superparamagnetic iron oxide nanoparticles and the water soluble drug not in the aqueous suspension; and S4, adding a carboxymethyl chitosan solutionfor hydration.

Description

technical field [0001] The invention relates to the technical field of pH-sensitive liposomes, in particular to a SPIO-traceable pH-sensitive drug-loaded liposome and a preparation method thereof. Background technique [0002] Liposome (liposome) refers to a bilayer lipid molecular microvesicle with a structure similar to a biological membrane, with a diameter ranging from 25 to 1000 nm, which can be used as a hydrophilic or / and hydrophobic drug carrier. It has the characteristics of targeting, lymphatic orientation, sustained release, reducing drug toxicity and improving drug stability. [0003] The rapid and disordered growth of solid malignant tumors leads to insufficient angiogenesis and insufficient blood oxygen supply, resulting in the appearance of hypoxic cells in the tumor. The presence of hypoxic cells leads to a lower pH value (6.5 or below) in the tumor interstitium than in normal tissue (7.4), which provides a theoretical basis for pH sensitive liposomes. pH-s...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/24A61K47/28A61K47/12A61K47/36A61K47/22A61K31/4168A61K31/337A61K33/24A61K31/704A61K49/08A61K49/12A61K49/18B82Y5/00B82Y15/00A61P35/00
CPCA61K9/1277A61K31/337A61K31/4168A61K31/704A61K33/24A61K47/12A61K47/22A61K47/24A61K47/28A61K47/36A61K49/08A61K49/126A61K49/1863A61P35/00B82Y5/00B82Y15/00
Inventor 李必波罗治彬何美李必强
Owner 重庆市人民医院
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