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Bionic nano preparation based on platelet membrane fragments as well as preparation method and application of bionic nano preparation

A bionic nano-platelet technology, applied in the field of medicine, can solve the problems of small tumor tissue and inability to produce EPR effect

Active Publication Date: 2020-10-20
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, drug delivery to residual tumor lesions or circulating tumor cells after surgery cannot be effectively accomplished by ordinary nano-drug delivery systems.
Because once most tumors are surgically eradicated, the remaining tumor tissue (<0.1g) will certainly be too small to produce an EPR effect

Method used

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  • Bionic nano preparation based on platelet membrane fragments as well as preparation method and application of bionic nano preparation
  • Bionic nano preparation based on platelet membrane fragments as well as preparation method and application of bionic nano preparation
  • Bionic nano preparation based on platelet membrane fragments as well as preparation method and application of bionic nano preparation

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preparation example Construction

[0058] In yet another specific embodiment of the present invention, the preparation method of the above-mentioned biomimetic nano-preparation is provided, including:

[0059] The Cdk5 inhibitor and the chemotherapeutic drug are respectively dissolved, mixed evenly, added into the aqueous solution containing platelet membrane fragments, stirred for treatment, and obtained after dialysis.

[0060] In yet another specific embodiment of the present invention, the solvent selected for dissolving is dimethyl sulfoxide, which has a better dissolving effect; at the same time, in order to make the Cdk5 inhibitor and chemotherapeutics mix more uniformly, it is preferable to use an ultrasonic method to improve both. uniformity of mixing.

[0061] In yet another specific embodiment of the present invention, the addition is carried out in a dropwise manner; thereby making the antitumor drug components more uniformly dispersed;

[0062] Stirring treatment time is 10-40min;

[0063] Dialys...

Embodiment 1

[0093] Example 1: Preparation of Platelet Membrane Fragments

[0094] 1) Extraction of peripheral blood from mice: After fixing the mice, the eyeballs were picked up with tweezers and removed quickly, and the blood flowed from the orbits into EP tubes rinsed with EDTA.

[0095] 2) Platelet extraction: the collected whole blood sample was centrifuged at 100 g for 20 min at room temperature to separate and remove red blood cells and white blood cells to obtain platelet-rich plasma. Centrifugation was repeated once more under the same conditions for purification. Add EDTA and prostaglandin E1 to the purified platelet-rich plasma, and centrifuge at 800 g for 20 min at room temperature to obtain platelet pellets. Platelet pellets were redispersed in PBS containing EDTA and protease inhibitor tablets (Roche) and stored frozen.

[0096] 3) Preparation of platelet cell membrane fragments: the platelet cell membrane was physically destroyed by probe ultrasound, the power amplitude of t...

Embodiment 2

[0097] Embodiment 2: Transmission Electron Microscopy (TEM) Identifying the Nanostructure of Platelet Membrane Fragments

[0098] Use a pipette gun to absorb 20 μL of platelet membrane fragment solution, carbon film copper grid, filter paper to absorb excess liquid, dry at room temperature, and place it under a transmission electron microscope for observation. The result is as figure 1 As shown in the transmission electron microscope pictures, it can be confirmed that the size of the newly prepared platelet membrane fragments is ~20nm, and the size is uniform and the dispersion is good.

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Abstract

The invention provides a bionic nano preparation based on platelet membrane fragments as well as a preparation method and application of the bionic nano preparation, and belongs to the technical fieldof medicine. By means of drug combination of a cyclin dependent kinase 5(Cdk5) inhibitor and a chemotherapeutic drug, on one hand, tumor cells are killed with chemotherapy, the immune system is activated, content of IFN-gamma is recovered, immunosuppression caused by postoperative stress is relieved, on the other hand, PD-L1 is down-regulated by the Cdk5 inhibitor, IFN-gamma related immune drug resistance is relieved, and through combination of the Cdk5 inhibitor and the chemotherapeutic drug, dual characters of IFN-gamma are changed, the downstream immunosuppressive action of the IFN-gamma is removed, and the positive effect of IFN-gamma is exerted; and meanwhile, the problem of postoperative targeted drug delivery is solved according to the biological trend characteristic of platelets,besides, with improvement of the preparation method, the preparation method of bionic nanoparticles based on the platelet membrane fragments is simple, the drug-loading efficiency is high, and therefore, the bionic nanoparticles have good practical application value.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a bionic nano-preparation based on platelet membrane fragments, a preparation method and application thereof. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Surgical resection is currently the first-line option for cancer treatment, but residual tumor cells are unavoidable after surgery, and some cells will dissociate into the peripheral blood circulation to form circulating tumor cells, resulting in postoperative recurrence and metastasis in a large number of patients. More and more evidence shows that the stress of tumor surgery destroys the host immune system,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K9/51A61K47/46A61K31/52A61K31/704A61P35/00
CPCA61K9/5176A61K31/52A61K31/704A61K45/06A61P35/00A61K2300/00
Inventor 栾玉霞李倩
Owner SHANDONG UNIV
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