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

A nano-carrier and drug-resistant technology, applied in the fields of polymer materials and medical engineering, can solve the risk of weakening the synchronization of hyperthermia and chemotherapy, increasing the side effects of chemotherapy drugs, and high non-targeted hyperthermia and chemotherapy synergy and other issues, to achieve the effect of reversing tumor drug resistance

Active Publication Date: 2018-09-14
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 for reversing tumor drug resistance and preparation method thereof
  • Composite prodrug nanocarrier for reversing tumor drug resistance and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0028] Weigh 100mg of polyhydroxypropyl methacrylate-polyethylene glycol copolymer, and react it with 20mg of carboxylated tetravalent platinum to obtain a macromolecular prodrug linked to tetravalent platinum through an ester bond, poly(methyl Hydroxypropyl acrylate-quaternary platinum)-polyethylene glycol, wherein the coupling rate of polyhydroxypropyl methacrylate and carboxylated tetravalent platinum is 90%.

[0029] Take 5mg of particle size as 8nm superparamagnetic nanoparticles MnFe 2 o 4 and 5mg of platinum macromolecule prodrug poly(hydroxypropyl methacrylate-tetravalent platinum)-polyethylene glycol, dispersed in 2mL of tetrahydrofuran / NN-dimethylformamide=1 / 1 mixed solution, and then The mixed solution was added dropwise to 20 times the volume of deionized water under the action of ultrasound, and then dialyzed in deionized water for 24 hours to remove the organic solvent to obtain the aqueous solution of the composite prodrug nanocarrier. The composite prodrug na...

Embodiment 2

[0031] Weigh 80 mg of poly-N-methylolacrylamide-polyethylene glycol copolymer, modify the hydroxyl group of poly-N-methylolacrylamide into hydrazine, and then react with 20 mg of doxorubicin hydrochloride to obtain Adriamycin-linked macromolecule prodrug, poly(N-hydroxyethyl methacrylate-doxorubicin)-polyethylene glycol, wherein the modified poly N-hydroxyethyl methacrylate and doxorubicin The connection rate is 86%.

[0032] Get 2mg of particle diameter and be the superparamagnetic nanoparticle Mn of 15nm 0.6 Zn 0.4 Fe 2 o 4 And 5mg of macromolecular prodrug poly(N-methylolacrylamide-doxorubicin)-polyethylene glycol, add in the mixed solution of 5mL tetrahydrofuran / dimethyl sulfoxide=1 / 1, then in ultrasonic The mixed solution was added dropwise to 10 times the volume of deionized water, and then dialyzed in deionized water for 24 hours to remove the organic solvent to obtain an aqueous solution of the composite prodrug nanocarrier. The composite prodrug nanocarrier was t...

Embodiment 3

[0034] Take by weighing 50mg of polyhydroxyethyl methacrylate-polyethylene glycol copolymer, react it with the methotrexate of 10mg, obtain the macromolecule prodrug that is connected with methotrexate by ester bond, poly(methyl Hydroxypropyl acrylate-methotrexate)-polyethylene glycol, wherein the coupling rate of polyhydroxyethyl methacrylate and methotrexate is 88%.

[0035] Get 2mg of particle diameter and be the superparamagnetic nanoparticle Mn of 12nm 0.4 Zn 0.6 Fe 2 o 4 And 4mg of macromolecule prodrug poly(hydroxypropyl methacrylate-methotrexate)-polyethylene glycol, add 4mL of tetrahydrofuran / NN-dimethylformamide=3 / 7 in the mixed solution, then in Under the action of ultrasound, the mixed solution was added dropwise to 20 times the volume of deionized water, and then dialyzed in deionized water for 24 hours to remove the organic solvent to obtain an aqueous solution of the composite prodrug nanocarrier. The composite prodrug nanocarrier was then lyophilized to obt...

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Abstract

The invention discloses a composite prodrug nanocarrier for reversing tumor drug resistance and a preparation method thereof, and belongs to the field of polymer materials and medical engineering. Thecomposite prodrug nanocarrier is formed by self-assembly of an amphiphilic pH-sensitive macromolecular prodrug and a superparamagnetic nanoparticle, and has a typical core-shell structure, the core of the composite prodrug nanocarrier is formed by coating a drug-coupled hydrophobic segment of an amphiphilic pH-sensitive macromolecular prodrug with the superparamagnetic nanoparticle, and the shellis formed by a hydrophilic segment of an amphiphilic pH-sensitive macromolecular prodrug. Since the composite prodrug nanocarrier uses the conditional responsive amphiphilic macromolecular prodrugtoreplace a conditional responsive amphiphilic macromolecule, the composite nanocarrier simultaneously has both efficient magnetic hyperthermia and targeted chemotherapy interference-free from magnetocaloric action, the magnetic hyperthermia and chemotherapy can be more effectively combined and targeted to tumor tissues, and effective reversal of tumor drug resistance can be ultimately achieved.

Description

technical field [0001] The invention belongs to the field of polymer materials and medical engineering, and in particular relates to a multifunctional nano-drug carrier, in particular to a prodrug nano-carrier for reversing drug resistance of tumor drugs, which combines magnetic hyperthermia and pH-responsive chemotherapy . Background technique [0002] The use of chemotherapeutic drugs to treat tumors is a routine means of tumor treatment at present, but clinical chemotherapy is often accompanied by the occurrence of tumor drug resistance, which is currently known as the most important reason for the failure of tumor chemotherapy. Tumor drug resistance can be divided into primary drug resistance and acquired drug resistance. Primary drug resistance means that tumor cells are not sensitive to certain chemotherapeutic drugs, and show drug resistance at the first administration. The acquired drug resistance is that after a period of chemotherapy, the remaining tumor cells ar...

Claims

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Application Information

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Patent Type & Authority Applications(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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