Capsaicine and doxorubicin combined dual-pH-response intelligent nano drug delivery system as well as preparation method and application thereof

A nano-drug delivery system and drug combination technology, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve problems such as clinical application restrictions, and achieve good dispersion and biosafety Sexuality, simple operation, and the effect of abundant functional groups

Active Publication Date: 2020-02-18
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, capsaicin has a strong irritant, which can stimulate mucous membranes and cause a series of symptoms such as nasal discharge, sneezing and coughing, so its clinical application is limited.

Method used

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  • Capsaicine and doxorubicin combined dual-pH-response intelligent nano drug delivery system as well as preparation method and application thereof
  • Capsaicine and doxorubicin combined dual-pH-response intelligent nano drug delivery system as well as preparation method and application thereof
  • Capsaicine and doxorubicin combined dual-pH-response intelligent nano drug delivery system as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] 1. The preparation of dual pH-responsive intelligent nano-drug delivery system for combined administration of capsaicin and doxorubicin, including the following steps:

[0034]Step 1: Put 0.1 g of polypropylene pyrrolidone, 0.3 g of cetyltrimethylammonium bromide, 60 mL of methanol and 90 mL of water into a beaker, and adjust the pH value to 10.0. Then add 0.12mL 3-aminopropyltriethoxysilane and 0.6mL ethyl orthosilicate to the above mixed system, and after magnetic stirring at room temperature for 2h, place the product in 150mL hydrochloric acid ethanol solution and stir at 70°C Reflux for 12 hours, centrifuge the obtained reaction product, wash, and vacuum-dry to obtain mesoporous silica nanospheres with amino groups on the surface; figure 1 As shown, the particle size of the prepared amino mesoporous silica nanospheres is about 140nm.

[0035] Step 2: Add 10 mg of amino mesoporous silica nanospheres to 20 mL of capsaicin ethanol solution with a concentration of 120 ...

Embodiment 2

[0050] 1. The preparation of dual pH-responsive intelligent nano-drug delivery system for combined administration of capsaicin and doxorubicin, including the following steps:

[0051] Step 1: Put 0.15g of polypropylene pyrrolidone, 0.45g of cetyltrimethylammonium bromide, 80mL of methanol and 120mL of water in a beaker, and adjust the pH value to 10.5. Then add 0.2mL 3-aminopropyltriethoxysilane and 1.0mL ethyl orthosilicate to the above mixed system, stir magnetically at room temperature for 3h, put the product in 160mL ethanol solution of hydrochloric acid, stir at 75°C Reflux for 14 hours, centrifuge the obtained reaction product, wash, and vacuum-dry to obtain mesoporous silica nanospheres with amino groups on the surface;

[0052] Step 2: Add 10 mg of amino mesoporous silica nanospheres to 20 mL of capsaicin ethanol solution with a concentration of 150 μg / mL, shake at room temperature for 80 min, and separate the supernatant by centrifugation; Calculate the concentration...

Embodiment 3

[0065] 1. The preparation of dual pH-responsive intelligent nano-drug delivery system for combined administration of capsaicin and doxorubicin, including the following steps:

[0066] Step 1: Put 0.2g of polypropylene pyrrolidone, 0.6g of cetyltrimethylammonium bromide, 90mL of methanol and 140mL of water in a beaker, and adjust the pH value to 11.0. Then add 0.3mL 3-aminopropyltriethoxysilane and 1.5mL ethyl orthosilicate to the above mixed system, stir magnetically at room temperature for 3.5h, put the product in 170mL ethanol solution of hydrochloric acid, 78°C Stir and reflux for 16 hours, centrifuge the obtained reaction product, wash, and vacuum-dry to obtain mesoporous silica nanospheres with amino groups on the surface;

[0067] Step 2: Add 10 mg of amino mesoporous silica nanospheres to 20 mL of capsaicin ethanol solution with a concentration of 180 μg / mL, shake at room temperature for 100 min, and separate the supernatant by centrifugation; Calculate the concentrati...

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Abstract

The invention discloses a capsaicine and doxorubicin combined dual-pH-response intelligent nano drug delivery system and a preparation method and application thereof. The preparation method comprisesthe following steps: synthesizing amino mesoporous silica nanospheres by a sol-gel method, and loading capsaicine in pore channels of the nanospheres; secondly, coating the surfaces of the mesoporoussilica nanospheres with chitosan, and then modifying the surfaces of the mesoporous silica nanospheres coated with chitosan with 4-formylphenylboronic acid; and finally, reversibly combining doxorubicin with phenylboronic acid through a boron ester bond to prepare the capsaicine and doxorubicin combined dual-pH-response intelligent nano drug delivery system. The mesoporous silica nanospheres are used as a drug carrier, so good dispersibility and biological safety are guaranteed; chitosan coating is carried out on the capsaicin-loaded mesoporous silica nanospheres, so that the surface functional groups of the drug are enriched while the drug is prevented from being leaked in advance. Capsaicine and doxorubicin are combined for use, so that the cell drug resistance generated by single doxorubicin treatment can be reduced, and the cytotoxicity of doxorubicin is synergistically enhanced.

Description

technical field [0001] The invention relates to the technical fields of nanomaterials, drug combination, drug loading, characteristic response, etc., and specifically relates to a dual pH-responsive intelligent nano drug delivery system for combination drug of capsaicin and doxorubicin and its preparation and application. Background technique [0002] Chitosan is a non-toxic, biocompatible polymer, and is a biodegradable material that has been approved by the Food and Drug Administration (FDA) for human use. Each structural unit of chitosan contains a primary amino group, which can provide reactive sites for various groups due to its active chemical properties. Furthermore, chitosan is insoluble in water at neutral and alkaline pH conditions, but at lower pH, chitosan becomes a water-soluble cationic polyelectrolyte. Therefore, the use of chitosan to encapsulate drugs reduces the leakage of drugs under physiological pH conditions. However, when the acidic pH condition of t...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K9/52A61K47/04A61K47/36A61K47/24A61K31/704A61K31/165A61P35/00
CPCA61K9/5115A61K9/5123A61K9/5161A61K31/165A61K31/704A61P35/00A61K2300/00
Inventor 高瑞霞王凤宋慧佳贺一晋郑龙
Owner XI AN JIAOTONG UNIV
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