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Protein-polymer composite nano-carrier and preparation method thereof

A nano-carrier and polymer technology, which is applied in the field of nano-preparation of anti-tumor drugs, can solve the problems of poor targeting effect and achieve the effects of easy storage, improved stability, and increased tumor targeting

Active Publication Date: 2015-05-20
JIANGSU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, according to the classification of "Pharmaceuticals" (Edited by Cui Fude, "Pharmacy" 2nd Edition, 2011:536.), these carriers are all passive targeting agents, and passive targeting agents can only use different organs in the body , the interception or phagocytosis of particles of different sizes by tissue or reticuloendothelial system, and the drug is delivered to the target site, and the targeting effect is not good

Method used

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  • Protein-polymer composite nano-carrier and preparation method thereof
  • Protein-polymer composite nano-carrier and preparation method thereof
  • Protein-polymer composite nano-carrier and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1: Preparation of bufotoxin-loaded ursodeoxycholic acid modified protein-polymer composite nanoparticles.

[0048] Weigh 3.5 mg bufalin, 5 mg stearylamine and 30 mg pluronic F127 and dissolve them in dichloromethane. Slowly add 60 mg of n-butyl cyanoacrylate (BCA) dropwise into 5 mL of dilute hydrochloric acid (0.1 M) containing 25 mg each of dextran 70 and Pluronic F68, and slowly add the mixed solution of dichloromethane into the system, Add dropwise while stirring. After stirring for 4 h, adjust the pH to neutral with sodium hydroxide, add 5 mg ursodeoxycholic acid-modified bovine serum albumin, and continue stirring for 1 h. Remove residual methylene chloride by rotary evaporation, centrifuge at 5000 rpm for 3 min, and pass through a microporous membrane to obtain a composite nanocarrier suspension containing bufotoxin-ursodeoxycholic acid-modified protein-polymer.

[0049] Add 30mg of mannitol and 30mg of trehalose to the bufafolin-ursodeoxycholic acid mo...

Embodiment 2

[0050] Example 2: Preparation of bufotoxin-loaded hyaluronic acid modified protein-polymer composite nanoparticles.

[0051] Weigh 10 mg bufalin and 10 mg stearylamine, respectively, and dissolve them in dichloromethane. Slowly add 100 mg of ethyl cyanoacrylate (ECA) dropwise to 10 ml of dilute hydrochloric acid (0.1M) containing 50 mg of dextran 70 and 50 mg of Pluronic F68, and slowly add the mixed solution of dichloromethane into the system, Add dropwise while stirring. After stirring for 4 h, adjust the pH to neutral with sodium hydroxide, add 20 mg of hyaluronic acid-modified bovine serum albumin, and continue stirring for 1 h. Remove residual dichloromethane by rotary evaporation, centrifuge at 5000 rpm for 3 min, and pass through a microporous membrane to obtain a suspension of bufotoxin-hyaluronic acid modified protein-polymer composite nanocarrier.

[0052] Add 50 mg of sucrose to the bufafolin-hyaluronic acid modified protein-polymer composite nanocarrier suspensio...

Embodiment 3

[0053] Example 3: Preparation of etoposide-glycyrrhetinic acid modified protein-polymer composite nanoparticles.

[0054] Weigh 30 mg etoposide, 3 mg stearylamine and 50 mg pluronic F127 and dissolve them in dichloromethane. Slowly add 210 mg of methyl cyanoacrylate (MCA) dropwise into 5 mL of dilute hydrochloric acid (0.1 M) containing 10 mg of dextran 70 and 10 mg of Pluronic F68, and slowly add the dichloromethane mixed solution into the system dropwise. Add and stir. After stirring for 4 h, adjust the pH to neutral with sodium hydroxide, add 5 mg glycyrrhetinic acid-modified bovine serum albumin, and continue stirring for 1 h. Remove residual dichloromethane by rotary evaporation, centrifuge at 5000 rpm for 3 min, and pass through a microporous membrane to obtain etoposide-glycyrrhetinic acid modified protein-polymer composite nanocarrier suspension.

[0055] Add 20 mg PEG 400 and 10 mg glycine to the etoposide-glycyrrhetinic acid-modified protein-polymer composite nanoc...

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Abstract

The invention discloses a protein-polymer composite nano-carrier and a preparation method thereof and relates to the field of nano preparations of antitumor medicines. The protein-polymer composite nano-carrier is designed and developed on the basis of the characteristics of a lipoprotein structure of a human body and comprises a polymer core and a hydrophilic protein shell; a targeting ligand can be flexibly modified according to the treatment requirement, so as to construct the protein-polymer composite nano-carrier with active targeting property; the in vivo stability of the medicine is improved; the tumor targeting property is increased. In order to increase the load rate of the protein on the polymer kernel, a cationic additive is added to the formula to prepare a cationic polymer nanoparticle; nano suspension is milk white liquid; spherical particles with relatively uniform distribution can be seen by scanning through a transmission electron microscope. A freeze-drying protective additive is added for freeze-drying the nano suspension to form powder, so that the protein-polymer composite nano-carrier is relatively easy to store and the stability is improved. The protein-polymer composite nano-carrier prepared by the method is uniform in particle size and good in stability; and a fat-soluble antitumor medicine can be effectively encapsulated.

Description

technical field [0001] The invention relates to the field of nano-preparation of anti-tumor drugs, in particular to a protein-polymer composite nano-carrier capable of carrying fat-soluble anti-tumor drugs and a preparation method thereof. Background technique [0002] Malignant tumor is second only to heart disease, threatening the second largest killer of human health and life in the world. At present, chemotherapy, surgery, and radiotherapy constitute the three major means of tumor treatment. [0003] Chemotherapy is a treatment method that kills tumor cells with chemical drugs. However, most chemotherapeutic drugs are fat-soluble drugs with poor water solubility, which greatly affects the curative effect of the drugs. In addition, due to the strong cytotoxicity of chemical drugs and the lack of targeting properties, they will cause relatively large toxic and side effects, bring pain to patients, and sometimes even cause treatment interruption. [0004] Most of the cur...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K45/00A61K47/42A61K47/32A61P35/00
Inventor 许颖金雪锋陈美钱晨
Owner JIANGSU UNIV
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