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Glucocorticoid-loaded nano-carrier as well as preparation and application thereof

A technology of glucocorticoids and nanocarriers, applied in the field of bioengineering, can solve problems such as poor targeting effect of lupus erythematosus, achieve good clinical application and transformation prospects, reduce expression, and simplify the preparation process

Pending Publication Date: 2020-08-07
RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Aiming at the above-mentioned technical problems in the prior art, the present invention provides a nanocarrier loaded with glucocorticoid and its preparation and application. A technical issue where drugs in technology are poorly targeted for systemic lupus erythematosus

Method used

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  • Glucocorticoid-loaded nano-carrier as well as preparation and application thereof
  • Glucocorticoid-loaded nano-carrier as well as preparation and application thereof
  • Glucocorticoid-loaded nano-carrier as well as preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1. Preparation and characterization of nanocarriers loaded with prednisolone sodium phosphate

[0033] (1) Preparation

[0034]Calcium phosphate core loaded with prednisolone disodium phosphate (PLP) was prepared by co-precipitation method:

[0035] The oil phase was formed from 14.5 ml cyclohexane and 6 ml Igepal CO-520. First, 600 μL of 2.5M CaCl 2 The solution was slowly added dropwise into 20mL oil phase to form a calcium phase. Then add 460μL 16.3mM Na 2 HPO 4 (a.q.) and 140μL of 60mM PLP (a.q.) mixture was slowly added dropwise to another 20mL oil phase to form a phosphorus phase, and 400μL of 20mM 1,2-oleoyl phosphatidic acid (1,2-dioleoyl phosphatidic acid, DOPA) solution was added . After stirring evenly, slowly add the calcium phase to the phosphorus phase, add 400 μL of 20mM DOPA, and mix and stir for 45 minutes. Subsequently, 40 mL of absolute ethanol was added to the above mixed microemulsion to break the emulsion. The mixture after demulsif...

Embodiment 2

[0041] Example 2. Uptake of prednisolone sodium phosphate-loaded nanocarriers by LPS-stimulated mouse macrophage cell line RAW264.7

[0042] (1) Preparation

[0043] Adopt the film hydration method to prepare the common liposome of drug-loading with embodiment 1, add fluorescent dye DiI (20-100 μ g) simultaneously and put into 500ml round-bottomed flask, prepare the liposome of loading prednisolone sodium phosphate with embodiment 1 afterwards A recombinant high-density lipoprotein nano-drug delivery system is obtained to obtain a recombinant high-density lipoprotein nano-drug delivery system loaded with fluorescently labeled prednisolone sodium phosphate.

[0044] (2) LPS stimulates the mouse macrophage cell line RAW264.7 to establish an in vitro inflammation model

[0045] Cells were plated on 24-well culture plates in advance with a cell density of 5*10^4. After waiting for the cells to adhere to the wall (about 2 hours), 100ng / ml of LPS was added according to the experime...

Embodiment 3

[0049] Example 3. In vivo targeting effect of nanocarriers loaded with prednisolone sodium phosphate on systemic lupus erythematosus MRL / lpr mouse model

[0050] (1) Preparation

[0051] Similar to Example 2, a lipid nano drug delivery system modified with a functional penetrating peptide loaded with fluorescently labeled DiR was prepared.

[0052] (2) In vivo imaging experiment of small animals to observe the distribution in the body:

[0053] MRL / lpr mice and MRL / mpj mice were divided into PBS group, DiI-CaP-LNC group and DiI-CaP-rHDL group, respectively. The mice in each group were administered by tail vein injection, and 2 hours later, they were anesthetized by intraperitoneal injection of chloral hydrate, and the tissues (brain, heart, spleen, lung, double kidney, and double lower limbs) were taken and placed in an in vivo imager, using the Maestro in vivo imaging system Take tissue imaging pictures.

[0054] The mouse grouping and dosing regimen were consistent with t...

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Abstract

The invention provides a glucocorticoid-loaded nano-carrier which comprises a glucocorticoid core composed of glucocorticoid and a calcium phosphate core. Lipidosome is contained on the periphery of the glucocorticoid core, and apolipoprotein is contained on the surface of the lipidosome. The invention also provides a preparation method of the nano-carrier. The invention also provides applicationof the nano-carrier in preparation of medicines for treating inflammation and macrophage-related immune diseases. The glucocorticoid nano-carrier disclosed by the invention can be used for effectivelytargeting inflammation-related macrophages, so that the entrapped glucocorticoid can be used for effectively reducing the level of macrophage inflammatory factors at a relatively low administration dosage and the lupus disease activity is effectively improved; side effects are effectively alleviated, and the safety is improved. The nano-carrier can be applied to treatment of systemic lupus erythematosus, the preparation process is simple, and the nano-carrier has broad clinical application and conversion prospects.

Description

technical field [0001] The invention belongs to the field of bioengineering, relates to a nano-biomedical material, in particular to a nano-carrier loaded with glucocorticoid and its preparation and application. Background technique [0002] Systemic lupus erythematosus (SLE) is a type of autoimmune disease caused by abnormal activation of the immune system, often accompanied by the production of pathogenic autoantibodies, involving skin, joints, kidneys, blood and other systems , is an important disabling and fatal disease, which brings a huge burden to society. In the pathogenesis of the disease, many links are involved, including abnormal immune tolerance of B cells, autoantibody production, immune complex deposition, complement activation, inflammatory response, and tissue damage. [0003] Many studies have shown that macrophages are involved in the pathogenesis and progression of lupus. M1-type macrophages cause repair abnormalities and persistent inflammatory respons...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/42A61K47/02A61K31/573A61P29/00A61P37/00A61P19/02A61P19/06A61P35/00A61P19/04
CPCA61K9/127A61K31/573A61K47/02A61K47/42A61P19/02A61P19/04A61P19/06A61P29/00A61P35/00A61P37/00
Inventor 吕良敬高小玲俞叶江淦宋清香马欣怡
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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