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Compound nano drug carrier system with tumor promotion target capability

A nano-drug carrier and targeting technology, which is applied in the field of medicine, can solve the problems of lack of in-depth research on the release behavior and mechanism of the release process, the lack of in-depth research on drug release kinetics, the real response to human trials, and the controlled release of carrier drugs. Capacitance, enhanced cell uptake, high drug loading effect

Pending Publication Date: 2018-08-21
HUBEI UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The research on cyclodextrin / mesoporous silicon drug carrier has made some progress in drug controlled release, but there are still many problems: (1) The release behavior and release process mechanism in the cyclodextrin / mesoporous silicon drug carrier system , Drug release kinetics lack of in-depth research
There is no good and recognized evaluation system with systematic and comprehensive analysis and test indicators as a guide; (3) The research on cyclodextrin / mesoporous silicon drug carrier system belongs to bioengineering, which is bound by objective conditions and ethics. Clinical trials It is difficult to carry out in a short period of time, and the controlled release of carrier drugs is limited to in vitro experiments and animal experiments. These results cannot fully and truly reflect the situation of human experiments, so it has brought a lot to the evaluation of cyclodextrin / mesoporous silicon drug carrier system. inaccuracy

Method used

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  • Compound nano drug carrier system with tumor promotion target capability
  • Compound nano drug carrier system with tumor promotion target capability
  • Compound nano drug carrier system with tumor promotion target capability

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Preparation and performance research of a composite nano-drug carrier system capable of initiating and targeting tumors, which is prepared by the following method:

[0051] S1. Preparation of MCM-41 Mesoporous Silicon Nanoparticles (MSN)

[0052] Dissolve 0.28g of sodium hydroxide and 1g of cetyltrimethylammonium bromide (CTAB) in 480mL of secondary water and raise the temperature to 80°C, then slowly add 5mL of tetraethyl orthosilicate (TEOS) dropwise into the system After dropping, continue to stir for 2h to produce a white precipitate. After the reaction, the product was centrifuged (9500r / min×10min), washed with secondary water and methanol several times, and vacuum-dried at 50°C to obtain the MSN containing the template CTAB (CTAB@MSN). If it is necessary to remove the template CTAB, reflux the obtained 0.5gCTAB@MSN in 160mL methanol containing 9mL concentrated hydrochloric acid for 48h, then wash and centrifuge several times with secondary water and methanol, and...

Embodiment 2

[0068] Preparation and performance research of a composite nano-drug carrier system capable of initiating and targeting tumors, which is prepared by the following method:

[0069] MSN, MSN-NH 2 , β-CD-NH 2 And the preparation of mPEG-CHO (ie S1, S2, S5 and S7) is the same as in Example 1.

[0070] S3. Preparation of D-gluconic acid grafted MSN (MSN-D-C 6 h 12 o 6 )

[0071] 4.0 g of D-glucose solution was adjusted to pH between 5-6 with PBS of pH=7.4, and 5.75 g of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC. HCl) and 3.45g N-hydroxysuccinimide (NHS), after ice-water bath activation 24h, add 1.5g MSN-NH 2 After reacting at room temperature for 24 hours, wash twice with water and twice with methanol, and dry in vacuum at 50°C for 24 hours to obtain MSN-D-C 6 h 12 o 6 .

[0072] S4. Preparation of MSN (MSN-O-O-A) of modified benzaldehyde

[0073] 1.0g MSN-D-C 6 h 12 o 6 Dissolve in 30ml DMSO, add 1.85g 2,4,6-trimethoxybenzaldehyde and 0.3g p-tol...

Embodiment 3

[0079] Preparation and performance research of a composite nano-drug carrier system capable of initiating and targeting tumors, which is prepared by the following method:

[0080] MSN, MSN-NH 2 , β-CD-NH 2 And the preparation of mPEG-CHO (ie S1, S2, S5 and S7) is the same as in Example 1.

[0081] S3. Preparation of D-gluconic acid grafted MSN (MSN-D-C 6 h 12 o 6 )

[0082] 2.0 g of D-glucose solution was adjusted to pH between 5-6 with PBS of pH=7.4, and 2.5 g of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC. HCl) and 1.75g ​​N-hydroxysuccinimide (NHS), after ice-water bath activation 24h, add 1.2g MSN-NH 2 After reacting at room temperature for 24 hours, wash twice with water and twice with methanol, and dry in vacuum at 50°C for 24 hours to obtain MSN-D-C 6 h 12 o 6 .

[0083] S4. Preparation of MSN (MSN-O-O-A) of modified benzaldehyde

[0084] 2.0g MSN-D-C 6 h 12 o 6 Dissolve in 60ml DMSO, add 2.5g 2,4,6-trimethoxybenzaldehyde and 0.4g p-tol...

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Abstract

The invention relates to a compound nano drug carrier system with tumor promotion target capability and a preparation method of the system. The preparation method comprises the steps of connecting a 2,4,6-trimethoxybenzene ring to the surface of a mesoporous silicon nanoparticle through an epoxy ester bond, adopting beta-cyclodextrin as a 'valve' material, capping the surface of the mesoporous silicon nanoparticle with the beta-cyclodextrin by a subject-object effect of the cyclodextrin and the benzene ring, and grafting benzaldehyde terminated PEG (polyethylene glycol) to the surface of the beta-cyclodextrin through a pH (potential of hydrogen) sensitive imine bond to construct the compound nano drug carrier system capable of performing targeted release of a drug in a tumor cell. The constructed PEG / beta-CD / MSN (polyethylene glycol / beta-cyclodextrin / mesoporous silicon nanoparticle) compound nano drug carrier system is high in drug loading capacity, has double pH sensitivity mechanismsand more efficient targeted administration capability in the cancer cell, and can effectively increase a utilization ratio of the drug, reduce toxic and side effects of the drug, and better achieve targeted controlled release treatment of a cancer.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a composite nano-drug carrier system with tumor-initiating and targeting capabilities and a preparation method thereof. Background technique [0002] In the study of cancer, people want to find a way to treat cancer tissue in a targeted manner to achieve the effect of targeted therapy. Tumor targeted therapy can be divided into three categories: biological targeted therapy, chemical targeted therapy, and physical targeted therapy according to the treatment principle. Among them, chemical targeted therapy has been widely studied because of its thorough principle, simple operation and excellent effect. [0003] For this reason, American scientists Hignchi and Zaffaroni proposed the concept of Drug Delivery Systems (DDSs) in the 1960s. A variety of carriers have been extensively studied, from simple microcapsules, vesicles, and liposomes to later organometallic framew...

Claims

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Application Information

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IPC IPC(8): A61K47/52A61K47/60A61K47/69A61K31/704A61K31/4745A61K31/337A61P35/00
CPCA61K47/52A61K47/60A61K47/6951A61P35/00A61K31/337A61K31/4745A61K31/704
Inventor 李草陈辉江兵兵陈重银
Owner HUBEI UNIV
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