Method for loading nano-drug based on modified bacteria, compound of nano-drug and application of compound in treatment of colon cancer

A technology of nano-drugs and complexes, which is applied in the field of biomedicine and can solve problems such as poor curative effect

Active Publication Date: 2021-09-10
HAINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In view of this, the present invention provides a method based on modified bacteria loading ursolic acid nanopar

Method used

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  • Method for loading nano-drug based on modified bacteria, compound of nano-drug and application of compound in treatment of colon cancer
  • Method for loading nano-drug based on modified bacteria, compound of nano-drug and application of compound in treatment of colon cancer
  • Method for loading nano-drug based on modified bacteria, compound of nano-drug and application of compound in treatment of colon cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment one: if figure 1 , a method for loading nanomedicine based on modified bacteria comprises the following steps:

[0032] (1) Preparation of ursolic acid nanoparticles (HU)

[0033] Prepare 1,4-dioxane (Dio) solution containing 2mol / mL ursolic acid (UA) and 1mol / L hydroxypropyl cyclodextrin (HPCD) respectively, slowly drop 5mL ursolic acid (UA) solution Add 5 mL of hydroxypropyl cyclodextrin aqueous solution and stir for 24 hours in the dark, dialyze in the dark and freeze-dry to obtain ursolic acid nanoparticles, wherein the average particle size of ursolic acid nanoparticles is 220 nm.

[0034] In another embodiment, the molar ratio of ursolic acid and hydroxypropyl cyclodextrin is 1:1 or 1:2.

[0035] (2) Preparation of surface-modified amantadine attenuated Salmonella typhimurium (SA)

[0036] Add 1×10 to 10mL aqueous solution reaction system 8 CFU of attenuated Salmonella typhimurium with 1 mg amantadine (AMA-NH 2 ), shaking at 180rpm for 2h at 37°C t...

Embodiment 2

[0039] Embodiment 2: The difference between Embodiment 2 and Embodiment 1 is that the input ratios of ursolic acid nanoparticles (HU) and the modified attenuated Salmonella typhimurium (SA) are different, and the drug loading is different as shown in Table 2.

[0040] Table 2 Effect of different ratios of ursolic acid nanoparticles and modified attenuated Salmonella typhimurium on drug loading

[0041] project SA@HU 0.6

Embodiment 3

[0044] Example 3: Characterization and testing of the compound drug SA@HU based on modified bacteria loaded with ursolic acid nanoparticles in Example 1

[0045] (1) Unmodified attenuated Salmonella typhimurium S, SA@H, SA@HU by scanning electron microscope 0.6 、SA@HU 1.2 、SA@HU 1.8 Do shape test

[0046] The result is as figure 2 It shows that the surface of attenuated Salmonella typhimurium modified by amantadine has been successfully loaded with ursolic acid nanoparticles, and with the increase of the input amount of ursolic acid nanoparticles, the adsorption amount on the surface of the bacteria increased significantly.

[0047] (2) Utilize the total number of bacterial colonies (CFU method) to the unmodified attenuated Salmonella typhimurium (S), SA@H, SA@HU of embodiment one 0.6 、SA@HU 1.2 、SA@HU 1.8 Perform cell viability test

[0048] The result is as image 3 It showed that compared with the unmodified attenuated Salmonella typhimurium (S), the amantadine-mod...

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Abstract

The invention discloses a method for loading a nano-drug based on modified bacteria. The method comprises the following steps: loading an ursolic acid nano-drug coated by hydroxypropyl cyclodextrin on attenuated salmonella typhimurium of which the surface is modified by amantadine by utilizing a supramolecular reaction, wherein 6.5-16.5 mg of ursolic acid nano-drug is loaded on the attenuated salmonella typhimurium of which the surface is modified by amantadine by 1 * 10<8> CFU, and the ursolic acid nano-drug comprises ursolic acid and hydroxypropyl cyclodextrin in a molar ratio of 2:1. According to the novel composite drug prepared by the method, the drug is transported to a tumor core anoxic zone by utilizing the natural hypoxia targeting type of bacteria, so that the loss of the drug during in-vivo transportation is reduced, and the availability of the drug is remarkably improved; and biological and chemical dual treatment is carried out on tumors, the obvious synergistic effect is achieved compared with chemotherapy medicine and bacteria physical mixed treatment, the growth of the tumors can be obviously inhibited, and the tumor recurrence situation is avoided.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a method based on modified bacteria loading nano-medicine and its compound and its application in the treatment of colon cancer. Background technique [0002] Malignant tumors are one of the deadliest cancers in the world today, and chemotherapy is the main method for clinical treatment of tumors, but some chemotherapy drugs have no obvious targeting, resulting in limited therapeutic effect, and poor biocompatibility, resulting in large side effects. For example, ursolic acid (Ursolic Acid, UA) has significant safety and efficacy in cancer treatment, but its strong hydrophobicity, poor solubility, fast metabolism and poor biocompatibility limit its further clinical application. [0003] Hypoxia at the tumor site is a unique feature of locally advanced solid tumors, and it is also the main reason for the increased dispersion distance between blood nutrients and tumor cells and the decre...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K9/51A61K35/74A61K47/40A61K47/54A61P35/00A61K31/56
CPCA61K31/56A61K9/5161A61K35/74A61K47/54A61K47/6939A61P35/00A61K2300/00Y02A50/30
Inventor 吴锡龙吴云娣吕超逸
Owner HAINAN UNIVERSITY
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