Drug-loaded delivery drug delivery system for treating systemic lupus erythematosus and preparation method thereof

A lupus erythematosus, systemic technology, applied in the field of biomedicine, can solve the problems of difficult transfection, tumorigenicity, viral vector side effects, immunogenicity, etc.

Pending Publication Date: 2020-09-25
森心(上海)科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In addition, primary T cells are different from cell lines and are extremely difficult to transfect. At present, gene transfection is mainly carried out through viral vector systems, but viral vectors have problems such as toxic side effects, potential immunogenicity, and tumorigenicity.

Method used

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  • Drug-loaded delivery drug delivery system for treating systemic lupus erythematosus and preparation method thereof
  • Drug-loaded delivery drug delivery system for treating systemic lupus erythematosus and preparation method thereof
  • Drug-loaded delivery drug delivery system for treating systemic lupus erythematosus and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

experiment example

[0112] I. Experimental method:

[0113] 1. Characterization of Nanoparticles

[0114] Illustratively, the following Example 1 was used to prepare PEALmiR125a nanoparticles for subsequent experiments, and the Nano-zs particle size analyzer was used to measure the particle size and potential of the nanoparticles. The transmission electron microscope (TEM) was used to observe the structure of the nanoparticles. NanoDrop2000 was used to determine the encapsulation efficiency of nanoparticles. Specifically, the prepared PEALmiR125a was ultracentrifuged, the parameters were set to: 15000 g, 30 minutes, and the supernatant was taken. NanoDrop 2000 was used to determine the concentration of RNA in the stock solution and supernatant of nanoparticles. Then calculate the encapsulation rate according to the following formula. Encapsulation rate (%)=(1-amount of RNA in supernatant / amount of RNA in initial stock solution)×100%. The solutions were placed at 37°C and 4°C, samples were taken ...

Embodiment 1

[0149] Example 1 Construction and application of mPEG-PLGA-PLL nano-delivery system containing miR-125a

[0150] Preparation by emulsification evaporation method: accurately weigh 10mg of mPEG-PLGA-PLL and dissolve it in 500μl of dichloromethane, then add 5nmol of miR-125a diluted in DEPC water and mix ultrasonically (2S, 2S, 300W) under ice bath conditions to make Colostrum, then quickly pour it into 5ml of F68 aqueous solution (1%, w / v) aqueous solution, ultrasonic emulsification again under ice bath conditions, vacuum rotary evaporation to remove organic solvents in the preparation, that is, miR-125a / PEAL(PEAL miR-125a ) Nanoparticles.

[0151] The obtained nanoparticles have a diameter of about 158nm and a surface charge of +0.01mV. And the nanoparticle size and dispersion coefficient did not change significantly within a week at 4°C and 37°C, showing good stability.

[0152] Select 10-week-old MRL / lpr mice of spontaneous systemic lupus erythematosus model and divide them in...

Embodiment 2

[0153] Example 2: Construction and application of mPEG-PLGA-PLL nano delivery system containing miR-146a

[0154] Volumetric volatilization method: accurately weigh 10mg mPEG-PLGA-PLL, dissolve it in 1ml tetrahydrofuran, and then inject it into 5ml DEPC water containing 5nmol miR-146a. Stir until the tetrahydrofuran volatilizes to obtain the nanoparticle solution (PEALmiR-146a).

[0155] Using the MRL / lpr mouse model, referring to Example 1, PEALmiR-146a (miR-146a dose of 1.5 mg / kg) nanoparticles were injected into the mice through the tail vein twice a week for 4 weeks. PBS and free miR-146a served as controls. The results showed that PEALmiR-146a treatment significantly reduced spleen and lymph node enlargement, reduced proteinuria, and improved lupus nephritis (P<0.05).

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Abstract

The invention provides a drug-loaded delivery system for treating systemic lupus erythematosus and a preparation method thereof. The drug-loaded delivery system is prepared from a nano delivery systemloaded with an SLE therapeutic drug, and the SLE therapeutic drug is selected from one of miRNA, a miRNA inhibitor and/ or an SLE immunosuppressor and a combination thereof.

Description

Technical field [0001] The invention relates to the field of biomedicine, in particular to a drug-loaded delivery drug delivery system for treating systemic lupus erythematosus and a preparation method thereof. Background technique [0002] Systemic lupus erythematosus (SLE) is an autoimmune disease caused by loss of autoimmunity and damage to its own tissues, accompanied by multiple system damage. At the same time, it can cause severe skin damage, such as butterfly erythema, subacute skin lupus erythematosus, discoid erythema, skin vasculitis (purpura), pigment changes (precipitation or loss), urticaria-like skin rash and bullous lupus erythematosus, etc. . [0003] At present, the pathogenesis of SLE mainly has the following explanations: ①Continuous overactivation of type I interferon (IFN) pathway; ②Continuous activation of DC cells; ③DNA hypomethylation in epigenetic regulation; ④Abnormal cytokine secretion; ⑤T cells Abnormal; ⑥The influence of other mechanisms such as estro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K47/32A61K45/00A61K9/06A61K47/26A61K47/36A61K47/38A61P37/02
CPCA61K9/0014A61K9/06A61K9/5138A61K9/5146A61K9/5153A61K45/00A61K47/26A61K47/32A61K47/36A61K47/38A61P37/02
Inventor 段友容张佳利陈传荣余坚
Owner 森心(上海)科技有限公司
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