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Preparation method of nano medicine controlled release system and product and application of system

A nano drug and system technology, applied in the field of medicine, can solve the problems of loss of targeting, short half-life of drug circulation, low bioavailability, etc., to reduce surface free energy, enhance anti-tumor effect, and good biocompatibility Effect

Inactive Publication Date: 2018-05-25
THE THIRD XIANGYA HOSPITAL OF CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the surface free energy of conventional nanocarrier particles is relatively high, so they are easily coated by immunoglobulins in biological matrices (such as plasma) to form a so-called "protein corona", which not only promotes the removal of them by the reticuloendothelial system, but also It will also cover the targeting molecules modified on the surface of nanoparticles and lose their targeting, which will lead to the short half-life of the drug in circulation, low bioavailability, low amount of drug that can effectively reach the lesion site, and poor therapeutic effect.
At present, in order to reduce the surface free energy of nano-drug carriers, polyethylene glycol (PEG) and polyethyleneimine (PEI) are usually used to modify nano-drug carriers to enhance their dispersion and biocompatibility, but these materials are used as external materials. The source material still has certain toxic and side effects, and it is difficult to avoid the removal of the drug carrier by the endothelial system, resulting in the defect of reduced targeting

Method used

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  • Preparation method of nano medicine controlled release system and product and application of system
  • Preparation method of nano medicine controlled release system and product and application of system
  • Preparation method of nano medicine controlled release system and product and application of system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] The preparation flow chart of this embodiment is as follows figure 1 Shown, its specific preparation steps are as follows:

[0029] (1) Preparation of nanoscale erythrocyte membrane vesicles (RM)

[0030] Take fresh anticoagulated whole blood from healthy people, centrifuge at 3000rpm for 5min, discard the upper layer of plasma and white blood cells and platelets; add 30 times the volume of 0.25×PBS hypotonic solution to lyse red blood cells, release hemoglobin, then centrifuge at 14000rpm for 10min, discard the upper layer of hemoglobin, collect For the red blood cell membrane at the bottom, add hypotonic solution PBS again to wash the red blood cell membrane until the supernatant is colorless, and collect the light red red blood cell membrane solution at the bottom. Take 50ul red blood cell membrane solution plus 1ml PBS, put it in an ultrasonic cleaner for 10min (350W), and then put the ultrasonic red blood cell membrane into a 400nm syringe filter to extract back a...

Embodiment 2

[0040] (1) Particle size and microscopic test

[0041] Nanoscale erythrocyte membrane vesicles (RM) prepared in Example 1, drug-loaded graphene oxide (GID), nano drug controlled release system (F-RGID) and the nano drug controlled release system (RGID) in comparative example 1 The size is tested, and the results are as follows figure 2 As shown, GID particle size: 167±11nm; RM particle size: 143±5nm; RGID particle size: 144±9nm; F-RGID particle size: 145±7nm.

[0042] The microscopic morphology of the drug-loaded graphene oxide (GID), nanoscale erythrocyte membrane vesicles (RM), and nano drug controlled release system (F-RGID) prepared in Example 1 is as follows: image 3 As shown, the GID has a sheet-like structure, the RM particle size is uniform, and the GID is successfully wrapped by the RM.

[0043] (2) Biocompatibility test

[0044]The hemolysis rate of the drug-loaded graphene oxide (GID) prepared in Example 1, the nano-drug controlled-release system (F-RGID) and t...

Embodiment 3

[0046] Example 3 Application of nano drug controlled release system in the treatment of tumors

[0047] Schematic flow chart of the nano-drug controlled release system in the treatment of rat tumors. Figure 6 As shown, the specific steps are as follows:

[0048] (1) Targeted research

[0049] The drug-loaded graphene oxide (GID) prepared in Example 1, the nano-drug controlled-release system (F-RGID) and the nano-drug controlled-release system (RGID) prepared in Comparative Example 1 were studied on targeting. BALB / c female nude mice (about 20 g) were subcutaneously injected with Hela cells (1×10 6 ). Tumor volume = length × width 2 / 2; when the tumor volume reaches 100mm 3 , the nude mice were randomly divided into the above three groups. 100 μl of PBS solution of GID, RGID, and F-RGID (prepared according to the concentration of DOX in the carrier as 1 mg / L) was injected through the tail vein. Using the red fluorescence of doxorubicin, the drug distribution in vivo was...

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Abstract

The invention discloses a preparation method of a nano medicine controlled release system. The preparation method comprises the following steps: (1) preparing a nanoscale red blood cell membrane vesicle, (2) preparing photosensitive drug-loaded graphite oxide, (3) preparing a target molecule and (4) preparing the nano drug controlled release system. According to the method, a protein crown of a nano carrier due to coating by certain in-vivo proteins can be avoided by embedding of a red blood cell vesicle; the activity of the target molecule is guaranteed; the red blood cell membrane vesicle exists in a human body, has good biocompatibility and no toxic and / or side effects and does not cause a rejection reaction; the red blood cell embedded vesicle can effectively reduce surface free energyof graphite oxide and improve dispersity of the nano drug controlled release system; graphite oxide is absorbed with a photosensitizer, namely indocyanine green; and together with photo-thermal treatment, an antitumor effect of the nano drug controlled release system can be further improved.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a nano drug controlled release system and its preparation method and application. Background technique [0002] The sustained and controlled release system of nano-drugs can effectively improve the utilization rate of drugs and reduce the toxic and side effects of drugs, which is a breakthrough in the development of modern medicine. Targeted nano-drug controlled release system is to carry out targeted group modification on nano-drug carrier to improve the selectivity of drug delivery and the effectiveness of disease treatment. However, the surface free energy of conventional nanocarrier particles is relatively high, so they are easily coated by immunoglobulins in biological matrices (such as plasma) to form a so-called "protein corona", which not only promotes the removal of them by the reticuloendothelial system, but also It will also cover the targeting molecules ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/46A61K47/04A61K47/22A61K31/704A61K41/00A61P35/00
CPCA61K9/5176A61K31/704A61K41/0052A61K41/0057A61K47/02A61K47/22A61K2300/00
Inventor 聂新民李建桂嵘王彦洁蒋海叶
Owner THE THIRD XIANGYA HOSPITAL OF CENT SOUTH UNIV
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