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Ph sensitive doxorubicin nanoliposome modified by folic acid-carboxymethyl chitosan

A technology of carboxymethyl chitosan and nanoliposomes, which can be applied in the directions of liposome delivery, organic active ingredients, medical preparations containing active ingredients, etc., can solve problems such as cardiotoxicity and side effects, and achieve stable performance and prolonged The effect of long cycle performance and production cost reduction

Inactive Publication Date: 2011-10-26
上海微纳科技有限公司
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  • Summary
  • Abstract
  • Description
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Problems solved by technology

[0002] Doxorubicin (Doxorubicin), also commonly known as doxorubicin, daunorubicin, is a clinically commonly used antibiotic antineoplastic drug, with a wide anticancer spectrum and wide curative effect, and can treat various tumors, but the drug is harmful to the heart It has serious side effects, especially severe heart damage, and side effects such as bone marrow suppression limit its clinical application

Method used

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  • Ph sensitive doxorubicin nanoliposome modified by folic acid-carboxymethyl chitosan
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  • Ph sensitive doxorubicin nanoliposome modified by folic acid-carboxymethyl chitosan

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Embodiment 1

[0024] Take soybean lecithin for injection 2g, cholesterol 0.5g, vitamin E 0.025g under aseptic condition. Put the above materials in a suitable container, add 100ml of absolute ethanol and ultrasonically shake until completely dissolved into a solution, transfer the above solution to a pear-shaped bottle, and rotate under reduced pressure in a constant temperature water bath to form a transparent light yellow film. Take 100ml of PBS (pH=4.0) buffer solution to elute, and wash the membrane slowly. After washing the membrane, use an ultrasonic cell pulverizer with a power of 200-300w, an interval time of 5s, an ultrasonic time of 3s, and a working time of 30min to ultrasonically pulverize, control the particle size between 50nm-200nm, filter and sterilize with a 0.22 micron filter membrane, and use PBS (pH=8.0) buffer solution to adjust its external water phase to pH=6.8, add 0.2 g of doxorubicin hydrochloride dissolved in 0.9% sodium chloride solution and hydrate for 3 hours, ...

Embodiment 2

[0026] Take egg yolk lecithin for injection 1.6g, cholesterol 0.4g, vitamin E 0.020g under aseptic condition. Put the above materials in a suitable container, add 80ml of absolute ethanol and ultrasonically shake until completely dissolved into a solution, transfer the above solution to a pear-shaped bottle, and rotate under reduced pressure in a constant temperature water bath until a transparent light yellow film is formed. Take 80ml of PBS (pH=4.0) buffer solution for eluting, and wash the membrane slowly. After washing the membrane, use high-pressure homogenization to circulate 10 times when the pressure parameter is 80MPa, adjust the outer water phase to pH=7.0 with PBS (pH=8.0) buffer solution, add 0.9% sodium chloride solution. 0.16 g of Bixing was hydrated for 3 hours, a certain amount of folic acid-carboxymethyl chitosan solution was added, and hydrated for 0.5 hour to obtain a folic acid-carboxymethyl chitosan modified pH-sensitive doxorubicin nanoliposome solution. ...

Embodiment 3

[0028] Take egg yolk lecithin for injection 0.4g, cholesterol 0.1g, vitamin E 0.005g under aseptic condition. Put the above materials in a suitable container, add 20ml of absolute ethanol and ultrasonically shake until completely dissolved into a solution, transfer the above solution to a pear-shaped bottle, and rotary evaporate under reduced pressure in a constant temperature water bath until a transparent light yellow film is formed. Take 20ml of PBS (pH=4.0) buffer solution to elute, and wash the membrane slowly. After washing the membrane, use an ultrasonic cell pulverizer with a power of 200-300w, an interval time of 5s, an ultrasonic time of 3s, and a working time of 30min to ultrasonically pulverize, control the particle size between 50nm-200nm, filter and sterilize with a 0.22 micron filter membrane, and use PBS (pH=8.0) buffer solution to adjust its external water phase to pH=7.4, add 0.04 g of doxorubicin hydrochloride dissolved in 0.9% sodium chloride solution and h...

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Abstract

The invention relates to pH sensitive doxorubicin nanoliposome modified by folic acid-carboxymethyl chitosan and its preparation method. The liposome provided in the invention comprises doxorubicin, phosphatide, cholesterol, vitamin E, folic acid-carboxymethyl chitosan. The prepared liposome has pH sensitivity, tumor targeting performance and long cyclic active targeting drug delivery functions.

Description

technical field [0001] The invention relates to a folic acid-carboxymethyl chitosan modified pH sensitive doxorubicin nano liposome and a preparation method thereof. Background technique [0002] Doxorubicin (Doxorubicin), also commonly known as doxorubicin, daunorubicin, is a clinically commonly used antibiotic antineoplastic drug, with a wide anticancer spectrum and wide curative effect, and can treat various tumors, but the drug is harmful to the heart It has serious toxic and side effects, especially serious heart damage, and side effects such as bone marrow suppression limit its clinical application. Over the years, scientists from various countries have been looking for effective ways to reduce its toxic and side effects, such as adjusting the dosage regimen, developing doxorubicin analogues with low cardiotoxicity, combining drugs and changing drug dosage forms to reduce its severe cardiotoxicity . The toxicity of liposome-encapsulated doxorubicin is 50-70% lower th...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/704A61K47/36A61P35/00
Inventor 钱秀珍徐云龙赵崇军王丽丹
Owner 上海微纳科技有限公司
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