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Cationic macromolecular proteolipid gene medicine carrier, preparation method and application

A gene drug and macromolecule technology, which can be used in inactive components of polymer compounds, gene therapy, drug combinations, etc., can solve the problems of high cytotoxicity, poor tumor targeting, and low transfection efficiency, and achieve simple preparation and operation. , reversal of drug resistance characteristics, strong tumor targeting effect

Inactive Publication Date: 2012-10-10
SHANGHAI INST OF ONCOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patented inventive material described in this patents allows scientists to create various forms (microencapsules) containing different materials like proteins or other agents inside them without losing their effectiveness due to external factors like solvents. It provides an effective way to deliver these microparticles into cellular environments while avoiding harmful side reactions caused by free radicals generated during transport process. Additionally, its unique properties allow for stable storage over time at room temperature, reduced drug leaks when stored together, and simplified manufacturing processes compared to current methods. Overall, this new type of material makes possible applications involving nucleus medicine, immunology, cancer therapy, diagnoses, treatments, and blood vessel imaging.

Problems solved by technology

This patented technical problem addressed in this patents relates to improving the safety and effectiveness of cancer treatment drugs while reducing side effects on normal tissues or cells. Current methods involve delivering them through various routes like injection into blood vessels, intravenous administration, pulsing agents, implants, surgery, radiation treatments, chemotherapies, biological response modifiers, and other ways but each suffers from drawbacks including being expensive, unstable, harmful to healthy individuals, complex processes involved, difficulty in manufacturing, and having potential negative impact upon drug efficacy. To overcome these issues, it would be necessary to find better solutions without compromising certain features found during current approaches.

Method used

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  • Cationic macromolecular proteolipid gene medicine carrier, preparation method and application
  • Cationic macromolecular proteolipid gene medicine carrier, preparation method and application
  • Cationic macromolecular proteolipid gene medicine carrier, preparation method and application

Examples

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Embodiment 1

[0044] Embodiment 1: This embodiment discusses the preparation method of transferrin-long chain alkyl quaternary ammonium salt:

[0045] Dissolve 10 mg of transferrin (Tf) in 10 ml of a mixed solution of deionized water and isopropanol (the volume ratio of water and isopropanol is 1:1); Ammonium chloride 100 mg was slowly added to the system; after stirring at room temperature for 24 hours, the reaction solution was dialyzed with deionized water for 3 days, and freeze-dried to obtain transferrin-hexadecyl quaternary ammonium salt (Tf-HQ) White powder 12.0mg.

[0046] Among them, dimethyl hexadecyl epoxypropyl ammonium chloride can be replaced by other long-chain alkyl quaternary ammonium salts, and other long-chain alkyl quaternary ammonium salts include dimethyl octadecyl epoxypropyl ammonium chloride Ammonium, Dimethylbehenylglycidyl ammonium chloride, Dimethyltetradecylglycidyl ammonium chloride, Dimethyldodecylglycidyl ammonium chloride.

Embodiment 2

[0048] This example discusses the effect of different ratios of transferrin-hexadecyl quaternary ammonium salt (Tf-HQ), tetradecyl carboxymethyl chitosan quaternary ammonium salt (TQCMC) and cholesterol on cations when the reverse evaporation method is adopted. Effect of particle size on macromolecular transferrin liposomes.

[0049] Co-dissolve Tf-HQ (protein molecular weight: 79,000), TQCMC and cholesterol in different proportions in dichloromethane, and mix well to obtain solution I; prepare deionized aqueous solution II, in which the ratio of solution I and solution II is 1:2 After the two solutions are mixed, fully ultrasonic emulsification, dichloromethane is distilled off under reduced pressure on a rotary evaporator to obtain a transferrin liposome solution. As can be seen from Table 2, adjusting the mass ratio of Tf-HQ and cholesterol can obtain transferrin liposomes of different particle sizes, and the particle size distribution of the cationic transferrin liposomes ...

Embodiment 3

[0054] This example mainly provides an example of preparing cationic transferrin liposomes using other lipid components.

[0055] Weigh transferrin-hexadecyl quaternary ammonium salt (Tf-HQ) (quaternary ammonium salt substitution degree is 90.0%, protein molecular weight is 79,000) 15.0mg, DOPE 12.0mg are dissolved in 3.0ml dichloromethane, Oscillate evenly to obtain solution I, put it into an eggplant-shaped bottle, distill it under reduced pressure on a rotary evaporator, and pass nitrogen gas from time to time until the dichloromethane is completely evaporated, then dry it in vacuum at room temperature for 24 hours, and then use it with 3.0 mg of water-soluble 5.0mL PBS (pH=7.4) buffer solution II of magnetic particles was ultrasonically hydrated for 10min (thin film method); or the above-mentioned solution I and solution II were blended and emulsified, ultrasonicated for 10min, and put into an eggplant-shaped bottle after forming a stable emulsion , distilled under reduced...

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Abstract

The invention discloses a cationic macromolecular proteolipid gene medicine carrier, a preparation method and an application, wherein the cationic macromolecular proteolipid gene medicine carrier is a macromolecular transferrin liposome prepared by transferrin-long-chain alkyl quaternary ammonium salt and a lipid ingredient in a mass ratio of (0.05 to 20): 1. The result of a gene transfection experiment indicates that the gene transfection efficiency of the macromolecular transferrin liposome in 293T cells, NIH-3T3 cells, liver cancer Huh-7 cells, SMMC-7721 cells, lung cancer A549 cells is equivalent to the gene transfection efficiency of a positive control, namely a cationic liposome Lipofectamine TM2000. The system of the cationic macromolecular proteolipid gene medicine carrier is good in biocompatibility, low in cytotoxicity, and capable of being used as an excellent non-viral gene medicine delivery carrier.

Description

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Claims

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Application Information

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Owner SHANGHAI INST OF ONCOLOGY
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