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Inflammation-targeted neutrophile granulocyte medicine delivery system and application thereof

A technology of neutrophils and drug delivery system, which is applied in the field of pharmaceutical preparations to achieve the effects of increasing drug concentration, improving drug efficacy, and increasing accumulation

Active Publication Date: 2014-12-24
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are some unresolved scientific issues in the loading of drugs or nano-preparations into neutrophils, such as the way of drug loading, the amount of drug, probe and imaging agent loaded on cells, the stability of loaded drugs in cells and the inherent physiology of cell carriers. maintenance of activity

Method used

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  • Inflammation-targeted neutrophile granulocyte medicine delivery system and application thereof
  • Inflammation-targeted neutrophile granulocyte medicine delivery system and application thereof
  • Inflammation-targeted neutrophile granulocyte medicine delivery system and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Example 1 The targeting and pharmacodynamic evaluation of the drug delivery system of paclitaxel liposomes loaded with different surface potentials on postoperative glioma mouse models

[0064] 1. Isolation and purification of bone marrow neutrophils

[0065] Prepare Percoll stock solution and 10×PBS at 9:1 (v / v) to make 100% Percoll, and dilute with 1×PBS to prepare 55%, 65%, 68% (v / v) Percoll separation solutions. According to the order of separation liquid density first heavy then light, slowly and evenly superimposed to prepare two layers of Percoll separation liquid of 55% and 65%, freshly extracted mouse tibial bone marrow cells were diluted with 1×PBS to prepare a single cell suspension, 1: 1 (v / v) was slowly and evenly added to the top of the previously prepared 55% and 65% Percoll separation liquid, and centrifuged at 1000 g for 30 min. Extract the bone marrow cells interlayered with 55% and 65% separation medium, add one volume of 1×PBS to wash and resuspend,...

Embodiment 2

[0114] Example 2 Targeting and Pharmacodynamic Evaluation of Levofloxacin-loaded Cationic Liposome Neutrophil Drug Delivery System to Streptococcus pneumoniae Mouse Model

[0115] 1. Preparation and characterization of drug-loaded neutrophil drug delivery system

[0116] The extraction and purification of neutrophils are the same as in Example 1, and 10 mg of levofloxacin is taken to prepare cationic liposomes loaded with levofloxacin, and the method is the same as in Example 1.

[0117] The drug loading and encapsulation efficiency were measured by HPLC, and the particle size and potential were measured by laser particle size analyzer, as shown in Table 6.

[0118] Table 6

[0119]

[0120] HPLC was used to measure the retention of three kinds of electric levofloxacin liposomes in neutrophils under different physiological conditions simulated in vitro, and the results are shown in Figure 8 It can be seen from the figure that in the process of simulating normal blood cir...

Embodiment 3

[0148] Implementation 3 Targeting and pharmacodynamic evaluation of ibuprofen-loaded cationic liposome neutrophil drug delivery system on mouse model of ear swelling

[0149] 1. Preparation and characterization of drug-loaded neutrophil drug delivery system

[0150] The extraction and purification of neutrophils are the same as in Example 1, and 5 mg of ibuprofen is taken to prepare ibuprofen-loaded cationic liposomes as in Example 1.

[0151] The drug loading and encapsulation efficiency were measured by HPLC, and the particle size and potential were measured by laser particle size analyzer, as shown in Table 9.

[0152] Table 9

[0153]

[0154] HPLC was used to measure the retention of three kinds of electric ibuprofen liposomes in neutrophils under simulated different physiological conditions in vitro, the results are shown in Figure 12 It can be seen from the figure that in the process of simulating normal blood circulation and chemotaxis of inflammatory factors, th...

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Abstract

The invention discloses an inflammation-targeted neutrophile granulocyte medicine delivery system and application thereof. The medicine delivery system comprises a neutrophile granulocyte and a therapeutic substance or detection substance directly to indirectly loaded inside or on the surface of the neutrophile granulocyte. The neutrophile granulocyte is taken as a medicine carrier, and a medicine is actively targeted to an inflammation part to improve the concentration of the medicine at the inflammation part. The neutrophile granulocyte reaching the inflammation part is abnormally activated under the stimulation of a cytokines, rapidly breaks up and dies in an all-direction form, so that the loaded medicine is rapidly released to the target part favorably, the treatment effect is improved, and the toxic and side effects are reduced.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an inflammation-targeted neutrophil drug delivery system and its application, in particular to a delivery system targeting inflammation sites using neutrophils as carriers. Background technique [0002] Inflammation refers to the physiological response of biological tissue to stimuli such as trauma, bleeding, or pathogenic infection, including symptoms such as redness, swelling, fever, and pain. Inflammatory response is an important defense mechanism of the innate immune system to remove harmful stimuli or pathogens and promote repair. According to the cause of the disease, it can be divided into infectious inflammation, non-specific inflammation and allergic inflammation. Infectious inflammation is inflammation caused by viruses, bacteria, or bacterial products, usually treated with antibiotics or antifungal drugs; nonspecific inflammation is the use of certain inflammat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/46A61K48/00A61K49/08A61P29/00A61K49/04A61K31/337A61K31/5383
CPCA61K45/00A61K45/06A61K47/46A61K49/0002A61K49/0097A61K49/04A61K49/1896A61K51/1203A61K9/1271A61K9/5068A61K31/192A61K31/337A61K31/5383A61K31/7105A61K31/711A61K38/19A61K38/22A61P29/00B82Y5/00C12N5/0642G01N2800/52A61K2300/00C07K14/715C07K2317/00G01N33/5047
Inventor 张灿薛敬伟赵泽恺张蕾温雅静
Owner CHINA PHARM UNIV
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