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Manganese dioxide and doxorubicin supported nanometer hydrogel and preparation and application thereof

A technology of nano-hydrogel and manganese dioxide, which is applied to preparations for in vivo experiments, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., to enhance the effect of tumor treatment and improve the ability of tumors Effect

Active Publication Date: 2019-10-22
DONGHUA UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Retrieval of domestic and foreign literature has not yet found any information on the loading of MnO 2 Preparation of PVCLNGs with DOX and its application in tumor MR imaging and UTMD-enhanced tumor chemotherapy

Method used

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  • Manganese dioxide and doxorubicin supported nanometer hydrogel and preparation and application thereof
  • Manganese dioxide and doxorubicin supported nanometer hydrogel and preparation and application thereof
  • Manganese dioxide and doxorubicin supported nanometer hydrogel and preparation and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] (1) PVCL-COOHNGs were synthesized by precipitation polymerization: First, 1.878g VCL (source: J&K Bailingwei, specification: 100g), 98.28mg BAC (source: Alfa Aesar, specification: 1g), 20mg SDS (source: Sigma Aldrich, specification: 1g) dissolved in 120mL water, in N 2 In a protected atmosphere, stir at 70°C for 30 min to fully mix the mixture. Slowly add initiator ACMA (70mg, 10mL water) (source: Japan Wako Pure Chemical Industry Co., Ltd., specification: 25g) dropwise in the mixture afterwards, after 8min, add the aqueous solution (0.108g, 25mL water) of AAC dropwise, in The reaction was stirred for 4 h, and cooled to room temperature after the reaction. Dialyze with a 12000 to 14000 dialysis bag to remove impurities, after which the solution is lyophilized and weighed.

[0069] (2) Dissolve 10mg of PVCL-COOHNGs powder in 30mL of water, add EDC (287.55mg, 3mL of water) dropwise to the PVCL-COOHNGs solution under stirring, after 30min, add NHS (172.635mg, 3mL of wate...

Embodiment 2

[0073]Get synthetic PVCL-COOHNGs, PVCL-NH among the embodiment 1 2 NGs, MnO 2 @PVCL NGs and DOX / MnO 2 Each 1mg of @PVCLNGs was diluted to 50μg / mL with ultrapure water for the measurement of surface potential and hydrodynamic diameter. As shown in Table 1, the potential of PVCL-COOHNGs is -8.21mV, PVCL-NH 2 The potential of NGs is 9.79 mV, and the change of potential from negative to positive proves that PVCL-NH 2 Successful synthesis of NGs. When MnO 2 After loading onto the hydrogel, the potential turns negative, demonstrating that MnO 2 Successful synthesis of @PVCL NGs. When MnO 2 After @PVCL NGs loaded the chemotherapeutic drug DOX, the potential increased and the hydrated particle size increased, which proved the successful loading of DOX.

[0074] Additionally, if image 3 Shown, DOX / MnO 2 The UV absorption peak of @PVCL NGs at 489nm also proves the successful loading of DOX. DOX / MnO 2 The hydrodynamic diameter of @PVCL NGs in various solutions (water, saline...

Embodiment 3

[0079] Determination of DOX / MnO by ICP-AES test method 2 The content of Mn element in @PVCL NGs, respectively prepare DOX / MnO with different Mn element concentration 2 @PVCL NGs solution and DOX / MnO 2 @PVCL NGs+GSH solution 2mL each (Mn element concentration is 0.1625, 0.2325, 0.465, 0.93 and 0.86mM, GSH concentration is 10mM). The T of the material under different Mn concentrations was determined by a magnetic resonance imaging analyzer 1 relaxation effects, such as Figure 6 , after calculating DOX / MnO 2 @PVCL NGs+GSH and DOX / MnO 2 r of @PVCL NGs 1 values ​​were 8.3313mM -1 the s -1 and 0.0444mM -1 the s -1 , indicating that DOX / MnO 2 The relaxation rate of @PVCL NGs is significantly enhanced in high-concentration GSH solution, which is due to the MnO 2 It is reduced to Mn in high concentration GSH solution 2+ , while Mn 2+ has a ratio of MnO 2 higher relaxation rate. The concentration of GSH in the tumor microenvironment is significantly higher than that in n...

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Abstract

The invention relates to a manganese dioxide and doxorubicin supported nanometer hydrogel and preparation and application thereof. The manganese dioxide and doxorubicin supported nanometr hydrogel isprepared by supporting manganese dioxide and drugs to poly-N-vinyl-epsilon-caprolactam nano hydrogel. The preparation method is simple, the product is easy to purify, and the cost is low. The nanometer hydrogel prepared by using the method is low in particle diameter, is uniformly distributed, and is high in water solubility, colloidal stability and biocompatibility. The nanometer hydrogel prepared by using the method can be used as a magnetic resonance imaging contrast agent, in the combination of an ultrasound-targeted microbubble destruction technology, proliferation of cancer cells can besignificantly inhibited, and the manganese dioxide and doxorubicin supported nanometer hydrogel has a potential application value in the field of tumor diagnosis and treatment.

Description

technical field [0001] The invention belongs to the field of nanomedicine diagnosis and treatment reagents and their preparation and application, in particular to a nano hydrogel loaded with manganese dioxide and doxorubicin and its preparation and application. Background technique [0002] Malignant tumors have the characteristics of fast growth, strong metastasis, and high recurrence rate, and have become the main killer that threatens human health. The integration of diagnosis and treatment can not only realize the early and accurate diagnosis of malignant tumors, but also achieve efficient cancer treatment and reduce drug side effects, which has become an important goal of modern medicine. In recent years, the rapid development of nanomedicine has opened up a new door for the integration of cancer diagnosis and treatment. [0003] The early diagnosis methods of tumors include ultrasound imaging, X-ray computed tomography imaging, positron emission computed tomography, a...

Claims

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Application Information

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IPC IPC(8): A61K49/18A61K49/12A61K41/00A61K9/06A61K47/34A61K31/704A61P35/00
CPCA61K9/06A61K31/704A61K41/0033A61K47/34A61K49/124A61K49/1803A61P35/00
Inventor 史向阳徐放朱建志张昌昌孙文杰杜联芳林丽洲
Owner DONGHUA UNIV
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