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Cisplatin prodrug-manganese dioxide nanoparticle drug delivery system and preparation method and application thereof

A technology of manganese dioxide and nano-drug loading, which is applied in the field of nano-materials and pharmaceutical preparations, can solve problems such as hindering the application of cisplatin drugs, multi-drug resistance, etc., and achieve enhanced cisplatin curative effect, simple and efficient cisplatin curative effect, and preparation The effect of simple method

Inactive Publication Date: 2020-06-02
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, cisplatin drugs are prone to multidrug resistance, which greatly hinders the clinical application of cisplatin drugs

Method used

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  • Cisplatin prodrug-manganese dioxide nanoparticle drug delivery system and preparation method and application thereof
  • Cisplatin prodrug-manganese dioxide nanoparticle drug delivery system and preparation method and application thereof
  • Cisplatin prodrug-manganese dioxide nanoparticle drug delivery system and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Weigh 40mg of manganese dioxide solid and dissolve it in 20mL of ultrapure water, place it in a water bath and ultrasonically sonicate for 10 hours to fully dissolve it, then centrifuge at a speed of 2000rpm for 10 minutes in a centrifuge to remove the precipitate to obtain an aqueous solution of manganese dioxide nanosheets Weigh 2.5mg of cisplatin prodrug and 100mg of soybean lecithin and dissolve in 8mL of ethanol, 8mL of methanol, 4mL of methylene chloride in a mixed solution, ultrasonically in a water bath for 5min, put it into a 100mL eggplant-shaped bottle and rotate for 20min to fully form a film after it dissolves , and then take an appropriate amount of hydrated glass beads (it is appropriate to cover the bottom of the bottle) and manganese dioxide nanosheet aqueous solution into the film-forming 100mL eggplant-shaped bottle, rotate for 20min without pressure, and suck the liquid into the centrifuge tube after the rotation The probe was ultrasonicated for 5 min...

Embodiment 2

[0033]Weigh 20 mg of manganese dioxide solid and dissolve it in 20 mL of ultrapure water, place it in a water bath and ultrasonically sonicate for 15 hours to fully dissolve it, then centrifuge it at a speed of 3000 rpm for 15 minutes in a centrifuge to remove the precipitate to obtain an aqueous solution of manganese dioxide nanosheets ; Weigh 2.5mg cisplatin prodrug and 200mg soybean lecithin and dissolve in 14mL ethanol, 2mL acetonitrile, 4mL dichloromethane mixed solution, water bath ultrasonic 15min, put into 250mL eggplant-shaped bottle after it dissolves and rotate for 30min to fully form a film , and then take an appropriate amount of hydrated glass beads (it is appropriate to cover the bottom of the bottle) and manganese dioxide nanosheet aqueous solution into the film-forming 250mL eggplant-shaped bottle, rotate for 30min without pressure, and suck the liquid into the centrifuge tube after the rotation Probe ultrasonication was carried out under an ultrasonic cell dis...

Embodiment 3

[0035] Weigh 10 mg of manganese dioxide solid and dissolve it in 20 mL of ultrapure water, place it in a water bath and ultrasonically sonicate for 24 hours to fully dissolve it, then centrifuge it at a speed of 4000 rpm for 20 minutes in a centrifuge to remove the precipitate to obtain an aqueous solution of manganese dioxide nanosheets Take 1mg cisplatin prodrug and 100mg soybean lecithin and dissolve in 14mL ethanol, 2mL methyl alcohol, in the mixed solution of 4mL methylene chloride, ultrasonic 15min in water bath, put into 500mL eggplant-shaped bottle after it dissolves and rotate 40min to fully film-forming, Then take an appropriate amount of hydrated glass beads (it is advisable to cover the bottom of the bottle) and manganese dioxide nanosheet aqueous solution into the film-forming 500mL eggplant-shaped bottle, rotate for 40min without pressure, and suck the liquid into the centrifuge tube after the rotation. The probe was ultrasonicated for 30 min under an ultrasonic c...

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Abstract

The invention discloses a magnetic resonance imaging (MRI)-mediated and cisplatin multi-drug resistance-reversible two-dimensional (2D) nanoparticle drug delivery system and a preparation method and application thereof. According to the invention, a phospholipid layer containing a cisplatin prodrug is modified on the surface of an MnO2(subscript) nanosheet to form a 2D nanoparticle drug delivery system, the macromolecular nano preparation can promote the uptake of platinum-based drugs by tumor cells through endocytosis, and MnO2(subscript) can perform an oxidation-reduction reaction with glutathione, so that the drug delivery system has the capacity of consuming the glutathione; the system plays a role in hyperpyrexia absorption in a near infrared region, and the generation of hyperthermiacan not only be used in photothermal therapy to kill tumor cells, but also further down-regulate the expression of multidrug resistance-associated protein 1; Mn ions generated by reducing the MnO2(subscript) with the glutathione have a T1 MRI effect, and the following information can be conveniently obtained, including tumor position, size, etc.; and the 2D nanoparticle drug delivery system belongs to the field of preparations, and can realize the function of promoting curative effects of the cisplatin by multiple mechanisms mediated by the MRI.

Description

technical field [0001] The invention belongs to the field of nanomaterials and pharmaceutical preparations, and in particular relates to a preparation method and application of a two-dimensional nanometer drug-loading system for reversible cisplatin drug resistance mediated by magnetic resonance imaging. Background technique [0002] Lung cancer is one of the major diseases that seriously threaten human life and health, with high morbidity and mortality. Non-small cell lung cancer accounts for about 80% of all lung cancers. Even if it is completely resected, its five-year survival rate is still very low. Despite remarkable advances in molecularly targeted therapy in NSCLC, only a small fraction of patients are eligible. Cisplatin-based chemotherapy remains the first-line treatment for most patients with NSCLC. [0003] The main mechanism of action of cisplatin is to covalently bind to DNA in the nucleus to form DNA adducts, hinder DNA replication and transcription, and tri...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/243A61K9/51A61K47/02A61P35/00A61K49/06B82Y5/00B82Y15/00
CPCA61K9/5115A61K47/02A61K49/06A61P35/00A61K33/243B82Y5/00B82Y15/00
Inventor 孙敏捷钱程根高放杨学
Owner CHINA PHARM UNIV