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Alginate-drug loaded nanoparticle-polycation microcapsule and preparation and application thereof

A technology of alginate and polycation, which is applied in the direction of antipyretics, drug combinations, and pharmaceutical formulas, and can solve the problem that metabolites in the capsule cannot diffuse out of the capsule, affecting the transfer of nutrients and metabolites, nutrients and oxygen supply Insufficient and other problems, to achieve superior immune isolation performance, maintain immune isolation performance, and avoid the effect of host immune response

Active Publication Date: 2018-11-06
AFFILIATED ZHONGSHAN HOSPITAL OF DALIAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among the many biological microcapsules, sodium alginate-polylysine microcapsules are used more often, but the main problem still faced in the clinical application of microcapsules is that after transplantation of microencapsulated cells in vivo, the initial effect of treatment is obvious, However, after a period of time, the curative effect declines. The essential reason is that the microcapsules implanted in the body will trigger the host’s immune response to form a fibrotic package, which will affect the material transfer of nutrients and metabolites. Insufficient oxygen supply, metabolites in the capsule cannot diffuse out of the capsule, resulting in loss of graft function and graft failure [4]
[0003] For this reason, from the perspective of resisting host inflammation, some researchers loaded poly(lactic-co-glycolic) acid (PLGA) carriers loaded with anti-inflammatory drugs (such as dexamethasone) into the inner core of microcapsules. middle [5] , trying to achieve anti-inflammatory effect through local release of drugs, but because the PLGA carrier is introduced into the inner core of the microcapsules, the hydrophilicity and hydrophobicity of the sodium alginate solution are changed, which affects the sphericity of the calcium alginate gel microspheres, while the sphericity of the microcapsules Poor is one of the key factors that trigger fibrotic encapsulation; the acidic products of PLGA degradation itself will stimulate the host inflammatory response and aggravate the fibrotic encapsulation of the graft; after the anti-inflammatory drugs are released from PLGA, they first gather in the inner core of the microcapsules, requiring Diffusion of microcapsules to exert anti-inflammatory effect
Therefore, this microencapsulation of PLGA nanoparticles loaded with anti-inflammatory drugs cannot effectively solve the problem of fibrotic encapsulation after transplantation.

Method used

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  • Alginate-drug loaded nanoparticle-polycation microcapsule and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] The amphiphilic chitosan material with a hydrophobic substitution degree of 4.5 and a cationic hydrophilic group substitution degree of 60 was prepared.

[0048] Cationic amphiphilic chitosan nanoparticles loaded with curcumin were prepared under sterile conditions.

[0049] Calcium alginate gel microspheres were prepared by high voltage electrostatic method under sterile conditions.

[0050] Immerse the microspheres in the polylysine solution (polylysine molecular weight 20kDa, the solution is prepared from physiological saline, the concentration is 0.5g / L), the volume ratio of microspheres and polylysine solution is 1:10, react for 5 minutes, Wash with saline three times.

[0051] Step 3) The prepared microspheres were then immersed in the curcumin-loaded cationic amphiphilic chitosan nanoparticle solution prepared in step 1), the volume ratio of the microspheres to the nanoparticle solution was 1:10, and the reaction was performed for 10 minutes. Wash three times. ...

Embodiment 2

[0067] The reference method was used to prepare hydrophobically modified amphiphilic sodium alginate materials.

[0068] The solution of amphiphilic sodium alginate nanoparticles loaded with curcumin was prepared under sterile conditions.

[0069] Calcium alginate gel microspheres embedded with porcine hepatocytes were prepared by orifice extrusion method, and the cell content in the microspheres was 5×107 / ml microspheres.

[0070] Immerse the microspheres in polylysine solution successively (polylysine molecular weight is 20kDa, the solution is prepared by physiological saline, the concentration is 0.5g / L), the volume ratio of microspheres and polylysine solution is 1:10, react for 10 minutes , washed three times with saline.

[0071] The microspheres prepared in step 4) were immersed in the curcumin-loaded amphiphilic sodium alginate nanoparticle solution prepared in step 2), the volume ratio of the microspheres to the nanoparticle solution was 1:10, reacted for 15 minutes,...

Embodiment 3

[0075] The amphiphilic chitosan material with a hydrophobic substitution degree of 3.5 and a cationic hydrophilic group substitution degree of 62 was prepared.

[0076] Cationic amphiphilic chitosan nanoparticle solution loaded with curcumin was prepared under sterile conditions.

[0077] Calcium alginate gel microspheres embedded with porcine islet cells were prepared by high-voltage electrostatic method, and each microsphere contained 1-2 islets.

[0078] With the method of embodiment 1, microsphere is successively immersed in polylysine solution (polylysine molecular weight 20kDa, and solution is prepared by physiological saline, concentration 0.5g / L), and the cationic amphipathic chitopolymer of loading curcumin In the sugar nanoparticle solution, react with 0.2% sodium alginate solution for 10 minutes after the secondary film-forming reaction, wash with normal saline, liquefy 55mM sodium citrate, wash with normal saline, and prepare APCcur microparticles embedded with isl...

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Abstract

The invention relates to an alginate-drug loaded nanoparticle-polycation microcapsule and preparation and application thereof. The microcapsule product is a spherical microcapsule with a particle sizeof 100 to 1000 microns. The structure of the microcapsule product is divided into two parts of a microcapsule membrane and an inner core. The microcapsule membrane is self-assembled layer by layer byalginate, drug-loaded nanoparticles and polycations to form a polyelectrolyte composite hydrogel film, and the inner core is a hydrogel or hydrosol environment containing animal cells. The microcapsule product is used as an immunosuppressive tool in embedding carriers for cell transplantation. Under the premise of ensuring the microcapsule strength and immuno-isolation performances, the surface roughness and surface charge of the microcapsule membrane can be reduced, the in-situ release of an anti-inflammatory drug on the surface of the microcapsule is realized, and the problem of fibrillation wrapping is solved from two aspects of stabilization of the microcapsule membrane by the drug-loaded nanoparticles and in-situ release of the anti-inflammatory drug for anti-inflammation.

Description

technical field [0001] The invention relates to a microcapsule product, in particular to an alginate-drug-loaded nanoparticle-polycation biological microcapsule product used for embedding biologically active substances and its preparation method and application. Background technique [0002] In the 1960s, Chang reported semi-permeable membrane microcapsules, pointing out that using them to embed biologically active substances such as proteins and enzymes and cells can maintain the activity of biological substances. [1] . In the early 1980s, Lim and Sun successfully prepared sodium alginate / α-polylysine semipermeable membrane microcapsules (abbreviated as α-APA microcapsules) for tissue / cell function defect diseases (such as diabetes), including Islet cells of Wistar rats were sealed and transplanted into diabetic WistarLewis rats to secrete and release insulin to regulate blood sugar [2] . This has promoted the rapid development of research on materials and preparation me...

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K47/36A61K47/34A61K45/00A61K31/12A61P29/00
CPCA61K9/1641A61K9/1652A61K9/1676A61K31/12A61K45/00A61P29/00
Inventor 于炜婷刘袖洞郑国爽梁珊珊王若雨
Owner AFFILIATED ZHONGSHAN HOSPITAL OF DALIAN UNIV
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