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Preparation method and application of multifunctional membrane-controlled targeting nano-carrier integrating tracing and targeted drug delivery effects

A technology of nanocarriers and targeting nanoparticles, which is applied in the field of preparation and application of nanocarriers, and can solve the problems of off-target, cumbersome and weak preparation procedures, etc.

Active Publication Date: 2018-04-03
SOUTH CENTRAL UNIVERSITY FOR NATIONALITIES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although surface modification and targeting design based on nanocarriers have been reported, there are some common problems: first, the function is single, that is, most material designs cannot take into account both targeting and effective controlled release capabilities, so that the drug cannot reach the target. Sufficient drug release or poor selectivity to lesions lead to off-target problems; second, the preparation process is cumbersome and the materials are expensive; third, poor biocompatibility, or the use of toxic raw materials or residues of harmful reagents
Aiming at the problems of toxic and side effects and low therapeutic effect caused by factors such as easy off-target, premature release or poor selectivity in the existing nano drug delivery system, the present invention uses MSN as the nano storehouse of the drug, and uses doxorubicin (Doxorubicin ) etc. as a model of anticancer drugs, with the help of the physiological responsiveness of natural materials, designed a multifunctional membrane-controlled nano drug delivery system to achieve the integration of targeting and multi-responsiveness, and effectively improve the drug delivery process. problems such as off-target or missed release, and provide a scientific basis for improving the therapeutic effect of anticancer drugs

Method used

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  • Preparation method and application of multifunctional membrane-controlled targeting nano-carrier integrating tracing and targeted drug delivery effects
  • Preparation method and application of multifunctional membrane-controlled targeting nano-carrier integrating tracing and targeted drug delivery effects
  • Preparation method and application of multifunctional membrane-controlled targeting nano-carrier integrating tracing and targeted drug delivery effects

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Embodiment 1 A kind of preparation of modified mesoporous silica nanoparticles, comprising the following steps in turn:

[0062] Take 1.2g of cetyltrimethylammonium bromide (CTAB), dissolve it in 180mL of ultrapure water, add 30mL of ethylene glycol (EG) and 7.2mL of ammonia water (25wt%) under stirring, and heat up to 60°C Continue to stir for 30min to make it evenly mixed. Then, 2.4 mL tetraethyl orthosilicate (TEOS) was quickly dropped into it with a constant pressure dropping funnel, stirred at 60°C for 2 hours, aged at 60°C for 24 hours, then left at 4°C overnight, and centrifuged at 15,000 rpm After centrifugation for 15 minutes, the solid was washed four times with ultrapure water and then four times with absolute ethanol, and then vacuum-dried at 45° C. for 24 hours to obtain mesoporous silica nanoparticles without template removal (MSN-CTAB).

[0063] Disperse 0.5 g of MSN-CTAB in an ethanol solution containing hydrochloric acid (consisting of 0.54 mL of 37 wt...

Embodiment 2

[0065] Example 2: Preparation of a multifunctional membrane-controlled targeting nanocarrier

[0066] Ultrasonic disperse 10 mg of the amino-modified mesoporous silica nanoparticles prepared in Example 1 in 10 mL of ultrapure water to make a nanoparticle dispersion, and then prepare hyaluronic acid and chitosan into 1 mg / mL solutions respectively (wherein chitosan is dissolved in dilute hydrochloric acid with pH=3.5).

[0067]Under magnetic stirring, slowly add 5 mL of the above-prepared hyaluronic acid solution dropwise into the nanoparticle dispersion, continue stirring for 12 hours, centrifuge at 15,000 rpm for 15 minutes, pour off the supernatant, add 10 mL of ultrapure water to disperse, wash, Centrifuge and pour off the supernatant, then add 10mL of ultrapure water to disperse, wash, centrifuge and pour off the supernatant to obtain nanoparticles coated with the first layer of polymers.

[0068] Then disperse the nanoparticles coated with the first layer of polymer in 1...

Embodiment 3

[0069] Example 3: Preparation of drug-loaded membrane-controlled targeting nanoparticles

[0070] 10 mg of doxorubicin was dissolved in 10 mL of phosphate buffer with a pH of 7.4 to prepare a 1 mg / mL solution. Then take 20mg of the amino-modified mesoporous silica nanoparticles prepared in Example 1 and disperse them in 10mL of the above-mentioned doxorubicin solution, then add 1mL of CdSe quantum dot solution (3.33×10 -6 mol / L), magnetically stirred for 24 hours to load anticancer drugs. Then centrifuge at 15000rpm for 15 minutes, pour off the supernatant, add 10mL ultrapure water to disperse, wash, centrifuge, pour off the supernatant again, add 10mL ultrapure water to disperse, wash, centrifuge, and pour off the supernatant to obtain drug-loaded nanoparticles. Disperse the above-mentioned drug-loaded nanoparticles in 20mL of ultrapure water, slowly add 10mL of 1mg / mL hyaluronic acid solution dropwise under magnetic stirring, then continue stirring for 12h, then centrifuge...

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Abstract

The invention belongs to the technical fields of preparation and applications of nano-carriers, and in particular discloses a preparation method and an application of a multifunctional membrane-controlled targeting nano-carrier integrating tracing and targeted drug delivery effects. With nano mesoporous silica (MSN) as a drug 'warehouse', a positively charged high molecular material and a negatively charged high molecular material as preparation materials of a gating membrane, and adriamycin (DOX), cis-platinum, imatinib, taxol and the like as model anti-cancer drugs, research contents mainlyinclude optimization and improvement of natural materials, construction and process optimization of the gating membrane, structural characterization of a nano complex, drug release kinetic characteristics of drug molecules under the control of the gating membrane, and the like. Meanwhile, in the combination with the tracing imaging function of a fluorescent quantum dot, drug delivery behaviors andanti-tumor effectiveness of the membrane-controlled nano drug delivery system undergo preliminary evaluation through in-vitro experiments. Based upon research results, references are provided for thedesign and preparation of the novel membrane-controlled nano drug delivery system.

Description

technical field [0001] The invention relates to the technical field of preparation and application of nanocarriers, in particular to a preparation method and application of a multifunctional membrane-controlled targeting nanocarrier with functions of tracing and targeted drug delivery. Background technique [0002] At present, although considerable progress has been made in the research and development of nano-drug delivery systems, their products are not ideal. How to achieve the best therapeutic effect of drugs is still a major challenge. In the design of the delivery system, the biggest advantage of nano-carriers such as nano-mesoporous silica (MSN), liposomes (Liposomes) and carbon nanotubes (CNTs) is that they have a high loading capacity for drugs and are ideal for drug storage. The "warehouse". But how to realize the intelligent "on-demand" release of drugs, that is, to control the drug from the warehouse to be fully responsive and effectively released, and to effect...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00A61K9/51A61K47/36A61K47/34A61K47/04A61K31/704A61P35/00
CPCA61K9/5115A61K9/5146A61K9/5153A61K9/5161A61K31/704A61K49/0067A61K49/0093
Inventor 胡燕柯磊卓玛肖新才
Owner SOUTH CENTRAL UNIVERSITY FOR NATIONALITIES
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