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Liposome-nanoparticle hybrids for treating chronic glomerulonephritis

A nanoparticle and complex technology, applied in the field of medicine, can solve the problems of low drug loading, low encapsulation rate, unfavorable CGN and so on

Pending Publication Date: 2020-12-15
SOUTHWEST UNIVERSITY FOR NATIONALITIES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to the only research reports and our previous studies, whether it is the selected prednisolone or triptolide model drug, when liposomes are used to entrap them respectively, the low encapsulation efficiency and low load Dosage is an unavoidable problem
Moreover, after some highly toxic drugs (such as triptolide) are entrapped in liposomes or nanoparticles, the burst release of drugs in the body is also a problem
At the same time, in the existing research reports, only a single drug anti-inflammatory treatment is considered, while the prevention and reversal of fibrosis in the course of the disease is ignored, which is not conducive to the prognosis of CGN. Fibrosis' dual regulation may enable effective treatment of CGN

Method used

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  • Liposome-nanoparticle hybrids for treating chronic glomerulonephritis
  • Liposome-nanoparticle hybrids for treating chronic glomerulonephritis
  • Liposome-nanoparticle hybrids for treating chronic glomerulonephritis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] Example 1 Integrin α8-modified liposome-PLGA nanoparticle complex PLGA-ILs / double drug loaded with double drug

[0079] (1) Preparation of nano core

[0080] Precisely measure 10mg PLGA and 3mg dexamethasone (DXMS) dissolved in 3mL acetone solution and vortex mix as the organic phase solution, and drop the organic phase solution into 15mL 1% poise The aqueous phase solution of Loxamer 188 (vortex stirring 1000r / min), stirred at room temperature for 15min, and was then rotary evaporated in a water bath at 37°C for 10min to remove the organic phase. To remove nanoparticles with larger particle size, centrifuge the solution at 8000r / min for 5min, recover the supernatant, and then centrifuge the recovered supernatant at 12000r / min for 10min, remove the free DXMS from the supernatant, and add 10mL of deionized water Resuspended to obtain the nano-core (PLGA / DXMS).

[0081] (2) Preparation of PLGA-LNHy / double drug

[0082] The membrane materials DOPE, DOTAP, cholesterol (C...

Embodiment 2

[0085] Example 2 Liposome-gold nanoparticle complex (Au-ILs / siRNA / DXMS) modified by integrinα8 loaded with siRNA / DXMS

[0086] (1) Preparation of nano core

[0087] Synthesis of siRNA: Design, synthesize and screen the effective fragment TGF-β1siRNA of the target gene. The synthesized target gene fragment must have a sulfhydryl group to make it easy to bind with AuNPs.

[0088] Precisely measure an appropriate amount of 0.11mg / mL of HAuCl 4 4H 2 O solution, stirred and heated to boiling, slowly added a certain volume of 34mM sodium citrate solution, continued to stir and heat for 10min, and then cooled and stirred for 15min to obtain a red AuNPs solution, which was sealed at 4°C and stored away from light.

[0089] Preparation of AuNPs-siRNA complex: Dilute 10pmol siRNA and AuNPs according to (1:0 or 1:1 or 1:2 or 1:5 or 1:10 or 1:20) different mass ratios, mix them, and store them at 37°C Incubate for 30 min to prepare AuNPs-siRNA complex, transfer the reaction product int...

Embodiment 3

[0094] Example 3 Integrin α8-modified liposome-MS nanoparticle complex (MS-ILs / two different model drugs) loaded with double drugs

[0095] (1) Preparation of nano core

[0096] Weigh a certain amount of cetyltrimethylammonium bromide (CTAB) and dissolve it in deionized water, add 0.3g sodium acetate, appropriate amount of ethanol and 1mol L -1 sodium hydroxide, stirred and heated up to a certain temperature until the solution was clear and transparent, added an appropriate amount of tetraethyl orthosilicate (TEOS) dropwise under stirring, stirred at a constant temperature and high speed for 2 hours, and then repeatedly centrifuged and washed with an appropriate amount of water and ethanol solution, Dry at room temperature. Weigh an appropriate amount of dried powder and suspend it in a concentrated hydrochloric acid-ethanol mixture (5:90) at 85°C for 24 hours at 85°C for 24 hours, continue to use appropriate amount of water and ethanol solution to repeatedly centrifuge and w...

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Abstract

The invention provides antibody-modified liposome-nanoparticle hybrids (Liposome-nanoparticle hybrids, LNHy) with a lipid shell and a nanoparticle core, which take charged nanoparticles as an inner core, and a liposome phospholipid bilayer with opposite charges is coated onto the surface to form a cell-like structure with a core-shell. The hybrids have targeting ability and can encapsulate an anti-inflammatory drug and an anti-fibrosis drug which have prevention and / or treatment effects on chronic glomerulonephritis, so that the effective treatment effect of double regulation and control on chronic glomerulonephritis is realized.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an antibody-modified double-drug-loaded liposome-nanoparticle complex and its application for treating chronic nephritis. Background technique [0002] Chronic glomerulonephritis (CGN) is a chronic glomerular lesion caused by multiple etiologies, which has the characteristics of high prevalence and strong concealment. When some patients are first diagnosed, the kidney damage is already in the irreversible stage. Immune inflammatory injury is the main pathogenesis of CGN. By inducing the deposition of immune complexes in the glomeruli, it gradually develops into renal fibrosis, eventually leading to chronic renal failure, which endangers the lives of patients. At present, there is no specific drug to cure CGN. In order to control the inflammatory response, long-term use of glucocorticoids or other immunosuppressive drugs is required. However, long-term use of the ab...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/24A61K47/28A61K9/51A61K47/34A61K47/02A61K31/573A61K31/401A61K31/7105A61P13/12
CPCA61K9/127A61K47/24A61K47/28A61K9/5153A61K9/5115A61K31/573A61K31/401A61K31/7105A61P13/12A61K2300/00Y02A50/30
Inventor 袁志翔刘春萍胡游方朋超何黎黎顾健
Owner SOUTHWEST UNIVERSITY FOR NATIONALITIES
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