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Preparation method of alginate/epsilon-polylysine/alginate biological microcapsule

An alginate gel, alginate technology, applied in microcapsule preparation, microsphere preparation, microcapsule and other directions, can solve the problem of limited application of sodium alginate/α-polylysine microcapsule, poor biocompatibility , high price and other problems, to achieve the effect of low cost, mild reaction conditions and safe use

Active Publication Date: 2011-06-22
ZHANGJIAGANG IND TECH RES INST CO LTD DALIAN INST OF CHEM PHYSICS CHINESE ACADEMY OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among the many biological microcapsules, sodium alginate / polylysine microcapsules are used more, and the microcapsule membrane material is chemically synthesized α-polylysine (the amide bond between lysine residues is made of α-amino and α-carboxyl condensation), but due to the high price of α-polylysine (300-400US$ / g), and the inherent poor biocompatibility of the material, it has certain toxicity, which greatly limits the use of algae. The clinical application of sodium lysate / α-polylysine microcapsules [Strand B L, Ryan TL, Veld P I, et al. Cell Transplant., 2001, 10: 263-275]

Method used

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  • Preparation method of alginate/epsilon-polylysine/alginate biological microcapsule

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Effect test

Embodiment 1

[0025] 1) Preparation by high-voltage electrostatic method [Qu Beibei, Yu Weiting, Liu Xiudong, etc., preparation of monodisperse calcium alginate microgel beads by high-voltage electrostatic method, Acta Chemical Industry, 2005, 56(8): 1547] for embedding Calcium alginate gel microspheres with CHO cells, the initial cell seeding density was 1×10 6 / mL sodium alginate solution.

[0026] 2) Under the condition of 37°C, immerse the calcium alginate gel microspheres prepared above into 0.05% (w / v), pH5.5, ε-polylysine (Mw10KDa) / normal saline solution, CHO / seaweed The volume ratio of calcium acid gel microspheres and ε-PLL solution was 1:40, reacted for 10 minutes to prepare ε-AP microcapsules, and then washed 3 times with normal saline.

[0027]3) Under the temperature condition of 37°C, immerse the ε-AP microcapsules prepared above in a sodium alginate (Mw200KDa) / 0.9% (w / v) NaCl solution with a concentration of 0.05% (w / v), CH0 / ε -AP microcapsules and sodium alginate solution ...

Embodiment 2

[0032] 1) Using high-voltage electrostatic method [Qu Beibei, Yu Weiting, Liu Xiudong, etc., preparation of monodisperse calcium alginate microgel beads by high-voltage electrostatic method, Acta Chemical Industry, 2005, 56(8): 1547] to prepare embedding Calcium alginate gel microspheres with hepatocytes-HepG2 cells, the initial cell seeding density was 1×10 6 / mL sodium alginate solution.

[0033] 2) Under the condition of 37°C, immerse the calcium alginate gel microspheres prepared above into 0.1% (w / v), pH6.5, ε-polylysine (Mw30KDa) / normal saline solution, HepG2 / seaweed The volume ratio of calcium acid gel microspheres and ε-PLL solution was 1:20, reacted for 15 minutes to prepare ε-AP microcapsules, and then washed 3 times with normal saline.

[0034] 3) Under the temperature condition of 37°C, immerse the ε-AP microcapsules prepared above in the sodium alginate (Mw300KDa) / 0.9% (w / v) NaCl solution with a concentration of 0.1% (w / v), HepG2 / ε The volume ratio of -AP microc...

Embodiment 3

[0038] 1) Using high-voltage electrostatic method [Qu Beibei, Yu Weiting, Liu Xiudong, etc., preparation of monodisperse calcium alginate microgel beads by high-voltage electrostatic method, Acta Chemical Industry, 2005, 56(8): 1547] to prepare embedding Calcium alginate gel microspheres with embryonic stem cells (ES) at an initial seeding density of 1×10 6 / mL sodium alginate solution.

[0039] 2) Under the condition of 37°C, immerse the calcium alginate gel microspheres prepared above into 0.2% (w / v), pH6.5, ε-polylysine (Mw50KDa) / normal saline solution, ES / seaweed The volume ratio of calcium acid gel microspheres and ε-PLL solution was 1:10, reacted for 15 minutes to prepare ε-AP microcapsules, and then washed 3 times with normal saline.

[0040] 3) Under the temperature condition of 37°C, immerse the ε-AP microcapsules prepared above in the sodium alginate (Mw400KDa) / 0.9% (w / v) NaCl solution with a concentration of 0.2% (w / v), ES / ε - AP microcapsules and sodium alginate ...

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Abstract

The invention provides a biological microcapsule, in particular relating to a preparation method of an alginate / epsilon-polylysine / alginate biological microcapsule (epsilon-APA microcapsule). Based on the characteristic that the highly polymerized multivalence-cationic epsilon-polylysine has a high electrostatic interaction with a substance with negative ions, the epsilon-polylysine is taken as amicrocapsule film material, and the alginate microcapsule is externally made into a coating film with slow-release performance to change the permeability and immune isolation of the biological microcapsule, so that the epsilon-APA microcapsule is used for the biological and medical fields such as the cell transplantation, the cell culture, the drug release, and the like.

Description

technical field [0001] The invention relates to biological microcapsules, in particular to a preparation method of alginate / ε-polylysine / alginate biological microcapsules. Background technique [0002] In the 1960s, Chang reported semi-permeable membrane microcapsules, pointing out that biologically active substances and cells such as proteins and enzymes can be embedded in them to maintain the activity of biological substances [Chang TMS.Semipermeablemicrocapsules, Science, 1964, 146: 524-525] . In the early 1980s, Lim and Sun successfully prepared sodium alginate / α-polylysine (alginate / α-polylysine) semipermeable membrane microcapsules (referred to as α -APA microcapsules), encapsulating islet cells of Wistar rats and transplanted into diabetic WistarLewis rats to secrete and release insulin to regulate blood sugar [Lim F, Sun A M. Microencapsulated islets bioartificialendocrine pancreas, Science, 1980, 210: 908- 910]. This has promoted the rapid development of research...

Claims

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Application Information

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IPC IPC(8): B01J13/20A61K9/50A61K47/36A61K47/34C12N11/04
CPCA61K9/5052B01J13/10A61K9/5036A61K2035/128
Inventor 马小军朱静于炜婷张英
Owner ZHANGJIAGANG IND TECH RES INST CO LTD DALIAN INST OF CHEM PHYSICS CHINESE ACADEMY OF SCI
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