A pH- and redox-sensitive nanoparticle

A technology of nanoparticles and cystamide diacrylic acid, which is applied in the direction of organic active ingredients, drug combination, powder delivery, etc., can solve the problems of low solubility, reduced activity, easy ring opening, etc., and achieve the effect of simple method and environmentally friendly process

Active Publication Date: 2017-04-26
上海德琪医药科技有限公司
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  • Summary
  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

[0004] Camptothecin (CPT) is a broad-spectrum antineoplastic drug, which has a good effect on gastrointestinal tumors (gastric cancer, colon cancer, rectal cancer), liver cancer, bladder cancer and leukemia. However, camptothecin and other antitumor Drugs also have obvious defects: such as poor water solubility, the lactone ring on the molecule is easy to open under neutral or alkaline conditions, resulting in a water-soluble carboxylate form, resulting in reduced activity, and after acidification, the carboxylic acid Salts reconvert to less soluble lactone forms

Method used

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  • A pH- and redox-sensitive nanoparticle

Examples

Experimental program
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Embodiment 1

[0024] Preparation of cysteamide diacrylic acid:

[0025] Add 40mL of acetone and 4.83g (0.049mol) of maleic anhydride into a three-necked flask with a nitrogen protection device, raise the temperature to 50°C, and wait until the maleic anhydride is completely dissolved, then slowly add a solution of cystamine in acetone (3.02g Cystamine was dissolved in 10 mL of acetone), reacted for 2 hours and cooled to room temperature, the solution was filtered, the precipitate was washed three times with acetone to obtain a white powdery solid, and finally dried in a vacuum oven at 40°C for 12 hours to obtain cystamide diacrylic acid.

Embodiment 2

[0027] Preparation of pH- and redox-sensitive nanoparticles:

[0028] Weigh 100mg viscosity average molecular weight is 6.03×10 4 Chitosan was dispersed in 100mL distilled water, 120mg was added by the obtained cystamide diacrylic acid in Example 1, the pH value of the mixed solution was adjusted to 5 after magnetic stirring for 2h, and 328mg1-(3 -Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 320mg N-hydroxysuccinimide, react at 25°C for 24h, put the solution in a dialysis bag (MWCO=8000-14000) and put it in distilled water Medium dialysis for 5 days (the water was changed every 4 hours on the first day, and the water was changed every 8 hours on the next 4 days), and finally the nanoparticle solution CS-CDMA-120 was obtained.

Embodiment 3

[0030] Preparation and in vitro release characterization of pH- and redox-sensitive drug-loaded nanoparticles:

[0031] Weigh 10mg of camptothecin and dissolve it in an aqueous solution of pH=12, stir for 12h, add it dropwise to 50mL of the aqueous solution of nanoparticles with a concentration of 1mg / mL, pH=12, obtained in Example 2, stir for 2h and then use 0.1M Slowly adjust the pH to 5 with hydrochloric acid, stir for 2 hours and then centrifuge for 10 minutes (10,000 rpm) to take the supernatant to obtain a pure drug-loaded nanoparticle solution. Measure the drug-loading efficiency and encapsulation efficiency of the obtained drug-loaded nanoparticles, then take 5mL drug-loaded nanoparticle solution, and carry out the test in 50mL glutathione (GSH) concentration respectively in PBS with pH=7.4 of 0, 10mM, and 20mM. For in vitro release, take 3mL of release medium at regular intervals and measure the absorbance at 368nm on a UV spectrophotometer, calculate the concentratio...

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Abstract

The invention discloses a preparation method of chitosan / cystamine diamide dicarboxylic acid nano particles with double pH / oxidation reduction sensitivities, and belongs to the technical field of carriers and sustained-release materials. The method comprises the steps of preparing cystic diamide dicarboxylic acid containing a disulfide bond, and then crosslinking chitosan in an aqueous solution by using the cystic diamide dicarboxylic acid as a crosslinker in the presence of an active agent to obtain narrowly distributed nano particles. Determination of the diameters of the nano particles under different pH value conditions proves that the nano particles have pH sensitivity. Camptothecin serving as a hydrophobic medicament is successfully carried by using the pH sensitivity of the obtained nano particles, and in-vitro release experiments using PBS (phosphate buffer solution) with different glutathione concentrations as mediums prove that the medicine-carrying nano particles have good reduction sensitivity.

Description

technical field [0001] The invention belongs to the technical field of carriers and slow-release materials, and relates to a preparation method and application of pH- and redox-sensitive nanoparticles. Background technique [0002] Polymeric nanoparticles have unique advantages in loading and controlling the release of anticancer drugs, thus arousing widespread interest of researchers. In order to realize the targeted delivery of drugs and the controlled release of in vivo conditions, more and more people focus on smart nanomaterials with functions of environmental response (such as pH, temperature, redox, magnetic response, etc.). [0003] In recent decades, reduction-sensitive polymeric biomaterials have gained rapid development as drug carriers due to their excellent responsiveness. These polymer drug carriers are designed based on the significant difference in intracellular and extracellular reduced glutathione (GSH) concentrations, and they usually contain disulfide bo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K31/4745A61K47/36A61P35/00C08J3/24C08B37/08
Inventor 倪才华奚林张丽萍陶蕾刘明杨期颐谭骏
Owner 上海德琪医药科技有限公司
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