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Chemical gene drug co-loaded targeting nano drug delivery system and preparation method thereof

A nano-drug delivery system, gene drug technology, applied in the direction of drug combination, drug delivery, gene therapy, etc., can solve the problems of application limitation, normal tissue toxicity, etc., and achieve the effect of high-efficiency treatment

Active Publication Date: 2020-09-08
NINGXIA MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, cationic carriers are more likely to be cleared by the reticuloendothelial system (RES) during blood circulation, and are prone to toxicity to normal tissues, which greatly limits their clinical application.
Therefore, it remains a challenge to balance the blood circulation stability of chemical / gene drug co-delivered nanoparticles and the effective release of the two drugs in cells.

Method used

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  • Chemical gene drug co-loaded targeting nano drug delivery system and preparation method thereof
  • Chemical gene drug co-loaded targeting nano drug delivery system and preparation method thereof
  • Chemical gene drug co-loaded targeting nano drug delivery system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Synthesis of PMet and HA-SH polymers.

[0062] 1. Synthesis of PMet.

[0063] Dissolve 700 μL of 4-styrene chloride in 2 mL of anhydrous tetrahydrofuran, then add 12 mg of 4-cyano-4-(thiobenzoyl)valeric acid and 1.5 mg of azobisisobutyronitrile, and freeze and thaw continuously with liquid nitrogen— After evacuating 3 times, the reaction solution was polymerized in an oil bath at 70°C under the protection of nitrogen. After 24 hours of magnetic stirring, the reaction was quenched with liquid nitrogen to stop the reaction. Petroleum ether was added to purify and precipitate the reaction solution 3 times, and polystyrene was obtained after vacuum drying. chlorine.

[0064] Dissolve 100mg of polystyrene chloride, 1.5g of metformin and 2mL of N,N-diisopropylethylamine obtained above in 5mL of dimethyl sulfoxide, and react in an oil bath at 130°C for 3 days. After the reaction, put The reaction product was transferred to a dialysis bag, dialyzed with 30 mmol / L hydrochloric a...

Embodiment 2

[0068] Synthesis of PMet and HA-SH polymers.

[0069] 1. Synthesis of PMet.

[0070] Dissolve 1.5mL of 4-styrene chloride in 5mL of anhydrous tetrahydrofuran, then add 35mg of 4-cyano-4-(thiobenzoyl)valeric acid and 8mg of azobisisobutyronitrile, and freeze and thaw continuously with liquid nitrogen - After evacuating 4 times, the reaction solution was polymerized in an oil bath at 80°C under the protection of nitrogen. After 36 hours of magnetic stirring, the reaction was quenched with liquid nitrogen to stop the reaction. The reaction solution was purified by adding petroleum ether 5 times, and after vacuum drying, polyphenylene was obtained. vinyl chloride.

[0071] Dissolve 150 mg of polystyrene chloride, 2.8 g of metformin and 3 mL of N,N-diisopropylethylamine obtained above in 8 mL of dimethyl sulfoxide, and react for 4 days in an oil bath at 140 ° C. After the reaction, the The reaction product was transferred to a dialysis bag and dialyzed with 100mmol / L hydrochloric...

Embodiment 3

[0075] Preparation of targeted nano drug delivery system co-loaded with chemical / genetic drugs.

[0076] In conjunction with the examples, the present invention uses immunotherapy gene interleukin-12 plasmid DNA (pIL-12) and cytotoxic drug doxorubicin (DOX) in combination, uses DOX to induce immunogenic death of tumor cells, regulates the immunosuppressive microenvironment, and assists pIL-12 works together to fight tumors. The preparation method of the targeted nano-preparation co-loaded with DOX / pIL-12 is as follows:

[0077] 10mg PMet (prepared by Example 1) polymer and 1mg DOX were dissolved in methanol respectively, after the two were mixed, slowly added dropwise to 1mL concentration in the Hepes buffer solution of 10mmol / LpH 7.4 and magnetic stirring, after the dropwise addition Continue to use magnetic stirring for 10 h to completely volatilize the organic solvent to obtain a DOX-PMet micellar solution with a DOX concentration of 1 mg / mL.

[0078] Add 1 mL of pIL-12 s...

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Abstract

The invention relates to a chemical gene drug co-loaded targeted nano drug delivery system and a preparation method thereof, and in particular relates to a tumor microenvironment hyaluronidase triggered allosteric-charge turnover type chemical / gene drug co-loaded targeted nano drug delivery system and a preparation method thereof. The nano drug delivery system is characterized by being co-assembled by co-loading chemical and gene drugs through a polystyrene-polydimethylbiguanide (PMet) cationic polymer by adopting hyaluronic acid-sulfydryl (HA-SH) with CD44 receptor targeting and tumor microenvironment hyaluronidase (HAase) sensitivity through electrostatic bonding and mercaptan chemical crosslinking. According to the invention, low-toxicity, targeted and efficient treatment of tumors be realized, and a novel multifunctional nano-carrier for treating tumors based on a chemical combined gene drug and a preparation application strategy are provided for anti-tumor research.

Description

technical field [0001] The invention relates to a targeted nano drug delivery system co-loaded with chemical genes and drugs and a preparation method thereof, in particular to a targeted nano drug delivery system for tumor microenvironment hyaluronidase triggering allosteric-charge reversal chemical / gene drug co-loaded Drug delivery system and method for its preparation. Background technique [0002] Cancer has become one of the most important diseases that endanger human health. Chemotherapy is currently the most widely used method for clinical treatment of cancer. However, chemical drugs usually have strong toxic and side effects, single-selective and long-term use will produce multidrug resistance and other problems, so single use of chemical drugs often cannot obtain the best curative effect. At present, more and more attention has been paid to the combination therapy of multiple drugs, especially the combination therapy of chemical drugs and gene drugs, in order to ac...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K47/69A61K47/61A61K45/00A61P35/00B82Y5/00B82Y40/00C08B37/08C08G73/00
CPCA61K48/0041A61K47/61A61K47/6935A61K45/00A61P35/00B82Y5/00B82Y40/00C08G73/00C08B37/0072
Inventor 刘艳华孙悦于双雨刘璐朱溶李莉
Owner NINGXIA MEDICAL UNIV
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