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Composite prodrug nanocarrier and preparation method for reversing tumor drug resistance

A nanocarrier, prodrug technology, applied in the fields of polymer materials and medical engineering, can solve the problems of tissue side effects, drug leakage, high risk of non-targeted hyperthermia and chemotherapy synergy, etc.

Active Publication Date: 2021-05-25
JIANGSU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] 1. The drug is easily leaked from the carrier by free diffusion
Since physical encapsulation or adsorption is a relatively weak force, when the drug carrier circulates in the body, the drug contained in it will slowly leak through free diffusion, thus weakening the synchronization of hyperthermia and chemotherapy
[0005] 2. There is a higher risk of non-targeted hyperthermia and chemotherapy synergy, which increases the side effects of chemotherapy drugs
This requires higher tumor targeting capabilities of drug carriers, but so far, tumor targeting recognition and distribution is still a worldwide problem
And this non-targeted thermochemotherapy can cause more serious side effects on normal tissues

Method used

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  • Composite prodrug nanocarrier and preparation method for reversing tumor drug resistance
  • Composite prodrug nanocarrier and preparation method for reversing tumor drug resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028]Those 100 mg of polymethyl methacrylate-polyethylene glycol copolymer reacts it with 20 mg of carboxylated tetravalent platinum to obtain macromolecular prodrugs attached by ester bond and tetrametin, poly (methyl) Acrylic - tetravalent platinum) - polyethylene glycol, wherein the coupling ratio of hydroxypropyl propyl polymethyl methacrylate and carboxylate is 90%.

[0029]Take 5 mg of particle diameter of 8 nm super-metallomagnetic nanoparticles MNFE2O4And 5 mg of platinum macromolecular prodrug poly (hydroxypropate - tetravalent platinum) - polyethylene glycol, dispersed in a mixed solution of 2 mL of tetrahydrofuran / NN-dimethylformamide = 1 / 1, then The mixed solution was added to 20x volume of deionized water under ultrasound, and then the organic solvent obtained the aqueous solution of the composite prior art diometric nanocarrier in deionized water. Then, the composite prior art nano carrier was lyophilized to obtain a powder solid. (Such asfigure 1The process flow diagr...

Embodiment 2

[0031]80 mg of poly N-hydroxymethyl acrylamide-polyethylene glycol copolymer, the hydroxyl group of the polyn-hydroxymethylacrylamide is used to form a combination amine, then react with a 20 mg hydrochloride, obtained by 腙 腙Macromolecular prodrug connection of doxorubicin, poly (n-methacrylate hydroxyethyl methacrylate) - polyethylene glycol, wherein the modified polyn-methyl methacrylate is an ethyl ester with doxorubicin. The association is 86%.

[0032]Take 2mg of superfluent magnetic nanoparticles Mn having a particle size of 15 nm0.6Zn0.4FE2O4And 5 mg macromolecular prodrug (N-hydroxymethylacrylamide-doxorubicin)-polyethylene glycol, add 5 mL of tetrahydrofuran / dimethyl sulfoxide = 1 / 1 mixed solution, then in ultrasound The mixed solution was added to the mixed solution, and then in deionized water was dialyzed in deionized water, the organic solvent was removed from the aqueous solution of the composite prior art nano-carrier. Then, the composite prior art nano carrier was lyo...

Embodiment 3

[0034]10 mg of polymethyl methacrylate-polyethylene glycol copolymer, react with 10 mg of methotrexate to obtain macromolecular prodrugs connected to methotrexate, poly (methyl) Harrative hydroxypropyl acrylate - methotrexate - polyethylene glycol, wherein the coupling ratio of hydroxyethyl methacrylate and methotrexate is 88%.

[0035]Take 2 mg of superfluent magnetic nanoparticles Mn having a particle size of 12 nm0.4Zn0.6FE2O4And 4 mg macromolecular prodrug poly (hydroxypropate-methotrexate)-polyethylene glycol, mixed solution of 4 mL of tetrahydrofuran / NN-dimethylformamide = 3 / 7, then Under ultrasound, the mixed solution was added to 20x volume of deionized water, and then dialyzed in deionized water for 24 hours, the organic solvent was removed to obtain aqueous solution of the composite prior art diometric nanocarrier. Then, the composite prior art nano carrier was lyophilized to obtain a powder solid. This product was dispersed in water at a lower concentration (0.1 mg / mL) i...

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Abstract

The invention discloses a composite prodrug nanocarrier for reversing drug resistance of tumor drugs and a preparation method thereof, belonging to the fields of polymer materials and medical engineering. The composite prodrug nanocarrier is composed of amphiphilic pH-sensitive macromolecular prodrugs and superparamagnetic nanoparticles through self-assembly, and has a typical core-shell structure. The hydrophobic segment of the macromolecular prodrug is formed by self-assembly and encapsulation of superparamagnetic nanoparticles, and its shell is composed of the hydrophilic segment of the amphiphilic pH-sensitive macromolecular prodrug. Since the composite prodrug nanocarrier replaces the condition-responsive amphiphilic macromolecule with a condition-responsive amphiphilic macromolecule prodrug, the composite nanocarrier has both high-efficiency magneto-thermal therapy and no interference from magneto-thermal effect. Targeted chemotherapy, so that magnetic hyperthermia and chemotherapy can be more efficiently combined and targeted to the tumor tissue, and finally achieve the effective reversal of tumor drug resistance.

Description

Technical field[0001]The present invention belongs to the field of polymer materials and medical engineering, and more particularly to a multifunctional nano-drug carrier, which specifically relates to a prodrug-resistant nanometric carrier for reversing a tumor drug resistance. .Background technique[0002]Treatment of tumors using chemotherapeutic drugs is currently a routine means of tumor treatment, but often accompanied by tumor resistance in clinical chemotherapy, which is currently known to lead to the failure of tumor chemotherapy. Tumors resistance can be divided into primary resistance and acquisition resistance. Primary resistance, tumor cells themselves are insensitive to certain chemotherapeutics, and the first medication exhibits drug resistance. The obtained resistance is after a period of chemotherapy, and the residual tumor cells exhibit resistance to the sensitivity of chemotherapeutic drugs. Although mechanism research confirms that tumor resistance is the result of...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K41/00A61K9/00A61K47/60A61P35/00
CPCA61K9/0009A61K41/0052A61K47/6935A61P35/00A61K2300/00
Inventor 屈阳辛渊蓉赖文龙王维许颖刘宏飞
Owner JIANGSU UNIV
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