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Tumor-targeting double-drug carrying and delivery system and preparation method thereof

A tumor-targeting, dual-drug-loading technology, which is applied in the field of biotechnology and pharmaceutical preparations, can solve the problems affecting tumor targeting efficiency and high concentration, and achieve the effects of high targeting and treatment efficiency, simple preparation, and small steric hindrance

Inactive Publication Date: 2012-04-04
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the concentration of endogenous transferrin (Tf for short) is very high, about 25 mM, which can compete with the drug delivery system with transferrin as the head group for the transferrin receptor on the surface of tumor cells, thus affecting the tumor targeting efficiency

Method used

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  • Tumor-targeting double-drug carrying and delivery system and preparation method thereof
  • Tumor-targeting double-drug carrying and delivery system and preparation method thereof
  • Tumor-targeting double-drug carrying and delivery system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Take 3 mg polyamide-amine (PAMAM, 77.35 mg / ml methanol solution) and dry it in a vial, add 0.73 mg polyethylene glycol (MAL-PEG3500-NHS, 1 mg / ml 0.035 M pH 8.0 phosphate solution) , the molar ratio of the two is 1:2, stirring and reacting at room temperature for 2 h, the NHS group reacts specifically with the amino group on the surface of PAMAM to make polyamide-amine-polyethylene glycol (PAMAM-PEG 2 ) complex solution, MWCO 10000 ultrafiltration centrifuge tube was ultrafiltered at 12000 rpm for 30 min to remove unreacted polyethylene glycol (PEG3500), and the synthesis of the carrier was characterized by hydrogen nuclear magnetic resonance.

Embodiment 2

[0040] Take 3 mg polyamide-amine (PAMAM, 77.35 mg / ml methanol solution) and dry it in a vial, add 0.73 mg polyethylene glycol (MAL-PEG3500-NHS, 1 mg / ml 0.035 M pH 8.0 phosphate solution) , the molar ratio of the two is 1:2, stirring and reacting at room temperature for 2 h, the NHS group reacts specifically with the amino group on the surface of PAMAM to make polyamide-amine-polyethylene glycol (PAMAM-PEG 2 ) complex solution, MWCO 10000 ultrafiltration centrifuge tube was ultrafiltered at 12000 rpm for 30 min to remove unreacted polyethylene glycol (PEG3500), reconstituted in pH 7.0 phosphate buffer, and added 0.10 mg polypeptide (T7, 2 mg / ml pH 7.0 phosphate solution), with a molar ratio of 1:1 to PAMAM, stirred at room temperature for 24 h, and the MAL group reacted specifically with the sulfhydryl group on the cysteine ​​residue of the polypeptide (T7) to make a polyamide— Amine-polyethylene glycol-polypeptide (PAMAM-PEG-T7) complex, ultrafiltration in MWCO 10000 ultrafil...

Embodiment 3

[0042] Take an appropriate amount of doxorubicin methanol solution and dry it in a vial, add phosphate buffer with a pH value of 7.4 to prepare a 3.48 μg / ml doxorubicin solution, take 0.5 ml in a centrifuge tube, and use LS-55 fluorescence The spectrometer was excited at 480 nm, and the fluorescence emission spectrum of doxorubicin was detected in the range of 520-680 nm.

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Abstract

The invention belongs to the field of biotechnology, and specifically, relates to a tumor-targeting double-drug carrying and delivery system and a preparation method thereof. The tumor-targeting double-drug carrying and delivery system adopts high-molecular materials, polyethylene glycol, a polypeptide, a treatment gene and a chemotherapeutic drug, wherein the polypeptide is utilized as a targeting head and the high-molecular materials are utilized as base high-molecular carriers. The preparation method comprises that the chemotherapeutic drug of adriamycin and the like are inserted into double chains of the treatment gene to form a gene-chemotherapeutic drug compound; and through electrostatic interaction between the gene chemotherapeutic compound and the base high-molecular carriers, the tumor-targeting double-drug carrying and delivery system which simultaneously carries the treatment gene and the chemotherapeutic drug is obtained. The high-molecular materials are novel polypeptide-modified high-molecular materials, are selected by a phage display technology, and can enter into cells by endocytosis, and thus the gene and chemotherapeutic drug intake capability of tumor cells are improved and safety is improved. The polypeptide (T7) as the targeting head has advantages belonging to transferrin, can effectively avoid interferences from endogenous transferrin, has high targeting and treatment efficiency, is easy for preparation, and can be further developed and be utilized for targeting treatment on other tumor tissue.

Description

Technical field [0001] The present invention is the field of biotechnology and drug preparations. It involves the release system of the drug loading and interpretation system.Its preparation method. Background technique [0002] Research on clinical tumor treatment shows that single drugs for tumor treatment can no longer treat tumors thoroughly.The cause of the analysis is that because tumor cells have certain regulatability, a single drug is given clinically for a long time, resulting in tolerance of tumor cells, causing drugs to lose tumor treatment, especially in simple chemotherapy.Weakness.Therefore, clinical attempts are used to use combined drug treatment to solve this problem.Family drug combination of chemotherapy can effectively prevent tumor cells from being tolerated and improve the treatment of drugs.The improvement of efficacy can reduce the dosage of the required drugs, thereby reducing the toxic and side effects of the normal tissue of the human body. [0003] At...

Claims

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Application Information

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IPC IPC(8): A61K47/34A61K47/42A61K47/48A61P35/00A61K31/513A61K31/704
Inventor 蒋晨韩亮黄容琴
Owner FUDAN UNIV
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