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In-situ magnetically-heated temperature-sensitive targeted nano drug carrier for reversal of multi-drug resistance in tumors

A nano-drug carrier and multi-drug resistance technology, which is applied in the fields of polymer materials and medical engineering, can solve the problem that the drug carrier does not have self-heating, etc., and achieve the effect of drug thermal sensitization and maximization

Inactive Publication Date: 2011-06-08
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although compared with traditional thermochemotherapy, the local heating caused by hyperthermia is a prerequisite for inducing the release of chemotherapeutic drugs in the corresponding local area, but the drug carrier itself does not have the ability of self-heating

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Weigh 50 mg polylactic acid and poly(N-isopropylacrylamide- co -Dimethacrylamide), 100 mg of superparamagnetic nanoparticles with a particle size of about 25 nm, and 10 mg of antineoplastic drug Melphalan, wherein the optimal TER temperature of the drug Melphalan is 41.5°C, by adjusting the composition Make the LCST of the copolymer and the Curie point of the magnetic nanoparticles reach 41.5°C, add 60 mL of tetrahydrofuran, and sonicate at room temperature for 10 min to fully disperse and dissolve the polymer, magnetic nanoparticles and drugs to form a transparent organic phase; The prepared organic phase solution was placed in a dialysis bag, and then dialyzed in 1 L of water for 24 hours, and the dialysate was changed every 3 hours. After the dialysis, the aqueous solution of drug-loaded micelles formed in the dialysis bag was collected, and then freeze-dried for 20 hours to obtain a powdery solid. The particle size distribution of the particles was measured with a...

Embodiment 2

[0032] Weigh 400 mg polylactic acid and poly(N-isopropylacrylamide- co -N-Hydroxyethylacrylamide), 100 mg of superparamagnetic nanoparticles with a particle size of about 15 nm, and 30 mg of antitumor drug cisplatin, in which the optimal TER temperature of cisplatin is 43 °C, By adjusting the composition so that both the LCST of the copolymer and the Curie point of the magnetic nanoparticles reached 43°C, 140 mL of tetrahydrofuran was added and ultrasonicated for 10 min at room temperature to fully disperse and dissolve the polymer, magnetic nanoparticles and drugs to form a transparent organic phase; the prepared organic phase solution was placed in a dialysis bag, and then dialyzed in 1 L of deionized water for 24 hours, and the dialysate was changed every 4 hours. After the dialysis, the aqueous solution of drug-loaded micelles formed in the dialysis bag was collected, and then freeze-dried for 48 hours to obtain a powdery solid. The particle size distribution of the part...

Embodiment 3

[0034] Weigh 200 mg of polylactic acid and poly(N-isopropylacrylamide- co - dimethylacrylamide), 50 mg of superparamagnetic nanoparticles with a particle size of about 19 nm, and 50 mg of antitumor drug doxorubicin. Adjust the composition so that both the LCST of the copolymer and the Curie point of the magnetic nanoparticles reach 43 °C, add 100 mL of tetrahydrofuran, and sonicate at room temperature for 20 min to fully disperse and dissolve the polymer, magnetic nanoparticles and drugs to form a transparent organic phase ; The prepared organic phase solution was placed in a dialysis bag, then dialyzed in 1 L of deionized water for 24 hours, and the dialysate was changed every 4 hours. After the dialysis, the aqueous solution of drug-loaded micelles formed in the dialysis bag was collected, and then freeze-dried for 48 hours to obtain a powdery solid. The particle size distribution of the particles was measured with a dynamic laser light scattering instrument, and the polyd...

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Abstract

The invention relates to an in-situ magnetically-heated temperature-sensitive targeted nano drug carrier for the reversal of multi-drug resistance in tumors, which can implement in-situ heating in tumor areas and simultaneously control the release of drugs, so that tumor cells having had drug resistance can be sensitive to chemotherapy drugs again under the double action of thermotherapy and chemotherapy, thereby realizing the reversal of multi-drug resistance of the tumor cells. The nano carrier is in a core-shell structure prepared from amphipathic temperature-sensitive copolymer, wherein the inner core layer is prepared from hydrophobic polylactic acid segments; the outer shell layer is prepared from hydrophilic temperature-sensitive polymer segments; and hydrophobic superparamagnetic nano particles and drugs are packed in the inner core layer. The nano drug carrier disclosed by the invention overcomes the defect of low chemotherapy drug distribution in tumor tissues in the existing process of thermotherapy-chemotherapy combined reversal of multi-drug resistance in tumors, and simultaneously satisfies the following two key factors for maximizing the thermotherapy and chemotherapy effects: the synchronicity of chemotherapy and thermotherapy and the controllability of the optimal temperature for chemotherapy and thermotherapy. The nano drug carrier disclosed by the invention can be well used for primary and acquired multi-drug resistance in tumors.

Description

technical field [0001] The invention belongs to the field of polymer materials and medical engineering, in particular relates to a multifunctional nano-medicine carrier, in particular to an in-situ magnetothermal temperature-sensitive targeting nano-medicine carrier for reversing multi-drug resistance of tumors. Background technique [0002] Chemotherapy is currently the most common means of cancer treatment, but due to the complexity of the pathogenesis of cancer, the effect of conventional chemotherapy on many tumors is poor, and the formation of tumor multidrug resistance (MDR) is the key factor for the failure of tumor chemotherapy. After a period of chemotherapy. Residual tumor cells are less sensitive to certain chemotherapeutic drugs, forming tolerance, and at the same time, cross-resistance to other anticancer drugs with different structures and mechanisms of action, which leads to the failure of chemotherapy. Therefore, how to reverse tumor multidrug resistance (M...

Claims

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Application Information

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IPC IPC(8): A61K47/34A61P35/00A61K47/32A61K47/02
Inventor 任杰屈阳李建波
Owner TONGJI UNIV
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