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

A tumor-targeting, dual-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 avoiding interference

Inactive Publication Date: 2013-04-10
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 using transferrin as the targeting 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 of polyamide-amine (PAMAM, 77.35 mg / ml methanol solution) and blow dry in a vial, add 0.73 mg of 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, and the reaction is stirred at room temperature for 2 h. The NHS group reacts specifically with the amino group on the surface of PAMAM to produce polyamide-amine-polyethylene glycol (PAMAM-PEG). 2 ) Complex solution, MWCO 10000 ultrafiltration centrifuge tube at 12000 rpm for 30 min to remove unreacted polyethylene glycol (PEG3500), and hydrogen nuclear magnetic resonance spectrum to characterize the synthesis of the carrier.

Embodiment 2

[0040] Take 3 mg of polyamide-amine (PAMAM, 77.35 mg / ml methanol solution) and blow dry in a vial, add 0.73 mg of 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, and the reaction is stirred at room temperature for 2 h. The NHS group reacts specifically with the amino group on the surface of PAMAM to produce polyamide-amine-polyethylene glycol (PAMAM-PEG). 2 ) Complex solution, MWCO 10000 ultrafiltration centrifuge tube at 12000 rpm for 30 min to remove unreacted polyethylene glycol (PEG3500), pH 7.0 phosphate buffer solution for reconstitution, add 0.10 mg of peptide (T7, 2 mg / ml pH 7.0 phosphate solution), the molar ratio with PAMAM is 1:1, and the reaction is stirred at room temperature for 24 hours. The MAL group reacts specifically with the sulfhydryl group on the cysteine ​​residue of the polypeptide (T7) to produce polyamide— Amine-polyethylene glycol-polypeptide (PAMAM-PEG-T7) complex, MWCO 10000 ultra...

Embodiment 3

[0042] Take an appropriate amount of doxorubicin methanol solution in a vial and blow dry, add a pH 7.4 phosphate buffer to make 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 adriamycin 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 invention belongs to the field of biotechnology and pharmaceutical preparations, and relates to a drug-loaded delivery system, in particular to a tumor-targeted dual-loaded drug delivery system, in particular to a tumor-targeted therapeutic gene and chemotherapy drug dual-loaded drug delivery system and its preparation method. Background technique [0002] Clinical tumor treatment studies have shown that a single drug for tumor treatment can no longer completely treat tumors. The reason for this analysis is that, due to the certain regulation of tumor cells, long-term administration of a single drug in clinical practice will cause tumor cells to develop tolerance and cause the drug to lose its therapeutic effect on tumors. Especially in simple chemotherapy, multidrug resistance is common. weakness. Therefore, clinical attempts to use combination drug therapy to solve this problem. Combination of chemotherapy drugs can effectively prevent tumor c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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