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Temperature-sensitive polypeptide encapsulated mesoporous silica intelligent drug carrier and preparation thereof

A mesoporous silica, temperature-sensitive technology, applied in the field of physical chemistry, can solve the problems of restricted application, cytotoxicity and refractory degradation, and achieve good biocompatibility and low leakage rate

Pending Publication Date: 2021-07-16
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some "gated" molecules have certain limitations such as cytotoxicity and refractory in vivo degradation, which restrict their further application.

Method used

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  • Temperature-sensitive polypeptide encapsulated mesoporous silica intelligent drug carrier and preparation thereof
  • Temperature-sensitive polypeptide encapsulated mesoporous silica intelligent drug carrier and preparation thereof
  • Temperature-sensitive polypeptide encapsulated mesoporous silica intelligent drug carrier and preparation thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Preparation of mesoporous silica nano drug carrier for polypeptide encapsulation based on Lpep.

[0039] (1) Preparation of mesoporous silica (MSN)

[0040] Prepare mesoporous silica (MSN), adopt sol-gel method, weigh 0.5g CTAB, place in a 500mL round bottom flask, add 240mL ultrapure water, ultrasonically dissolve for 20min, add dropwise 1.75mL of 2M NaOH solution, Raise the temperature to 80°C, stir for 30 minutes, use a constant flow pump to add 2.5mL of TEOS dropwise, set the dropping time to 12 minutes, then increase the stirring speed to 500r / min, react at 80°C for 2h, and then let it stand until room temperature. After standing and aging, centrifuge with a centrifuge, discard the supernatant, and repeatedly wash with ethanol and deionized water until the supernatant is neutral. A white product was obtained, which was transferred to an 80° C. vacuum oven for drying for 24 h.

[0041] (2) Synthesis of MSN-SH

[0042]Weigh 100mg of the MSN prepared in ...

Embodiment 2

[0049] Example 2 Preparation of nano drug carrier encapsulated based on Spep polypeptide

[0050] (1) Preparation of mesoporous silica (MSN)

[0051] Prepare mesoporous silica (MSN), adopt sol-gel method, weigh 0.5g CTAB, place in a 500mL round bottom flask, add 240mL ultrapure water, ultrasonically dissolve for 20min, add dropwise 1.75mL of 2M NaOH solution, Raise the temperature to 80°C, stir for 30 minutes, use a constant flow pump to add 2.5mL of TEOS dropwise, set the dropping time to 12 minutes, then increase the stirring speed to 500r / min, react at 80°C for 2h, and then let it stand until room temperature. After standing and aging, centrifuge with a centrifuge, discard the supernatant, and repeatedly wash with ethanol and deionized water until the supernatant is neutral. A white product was obtained, which was transferred to an 80° C. vacuum oven for drying for 24 h.

[0052] (2) Synthesis of MSN-SH

[0053] Weigh 200 mg of the MSN prepared in the above step 1), put...

Embodiment 3

[0060] Example 3 Research on Drug Controlled Release of Mesoporous Silica Drug Carrier Blocked by Polypeptide.

[0061] (1) The temperature-sensitive performance test of the polypeptide, the secondary structure of the polypeptide Lpep and Spep was tested by circular dichroism chromatography, and the aqueous solution of 40 μM Lpep and the aqueous solution of 40 μM Spep were respectively prepared. The detection wavelength range was 180-260nm, and the temperature was set at 25°C -70°C, the heating rate is 2°C / time. Figure 4(A) and 4(B) The changes of the secondary structure of Lpep and Spep with temperature are given respectively, and the change of the secondary structure with temperature can be seen. The phase transition temperature is given by the global 3 software, and the phase transition temperature of Lpep: 47.1±5.2°C , the phase transition temperature of Spep: 43.4±4.8°C.

[0062] (2) Drug controlled release test.

[0063] In order to study the release behavior of this...

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Abstract

The invention provides a temperature-sensitive polypeptide encapsulated mesoporous silica intelligent drug carrier and a preparation method thereof. The temperature-sensitive polypeptide encapsulated mesoporous silica intelligent drug carrier is formed by packaging temperature-sensitive polypeptide and mesoporous silica. Two polypeptides with different sequences are provided, the secondary structures of the polypeptides change along with temperature rise, the polypeptides have relatively mild phase change temperature, and the polypeptides are modified to the surface of a mesoporous nano material through disulfide bonds formed by sulfydryl of cysteine, so that drug encapsulation is realized. The polypeptides can extend a polypeptide chain to realize drug diffusion when the temperature rises, and the disulfide bond can be selectively cracked by reducing reagents GSH, TCEP, DTT and the like. Along with the change of the temperature and the concentration of glutathione, targeted drug release can be realized at a diseased region, or the glutathione can be used for directional release in other fields.

Description

technical field [0001] The invention belongs to the field of physical chemistry, and in particular relates to a temperature-sensitive polypeptide-encapsulated mesoporous silicon dioxide drug carrier and a preparation method thereof, which are used for controlled release in response to temperature and reduction. Background technique [0002] At present, cancer has become one of the major diseases threatening human health, and the treatment situation is grim. Among them, chemotherapy is an effective treatment method, but it also has relatively serious toxic and side effects, which often bring great pain to patients. The nano drug delivery system can realize the targeted drug delivery and controlled release of chemotherapy drugs, greatly reducing the side effects on normal tissues. Mesoporous silica nanomaterial is a new type of material with a pore size between 2nm and 50nm. It has the characteristics of large specific surface area, rich pore structure, easy surface modificati...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/42A61K47/04A61K31/704A61P35/00
CPCA61K47/42A61K47/02A61K31/704A61P35/00
Inventor 徐首红徐俊马佳奇宋佳李高阳刘洪来
Owner EAST CHINA UNIV OF SCI & TECH
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