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Targeting responsive release system and preparation method and application thereof

A release system and responsive technology, applied in pharmaceutical formulations, organic active ingredients, non-central analgesics, etc., can solve the problems of other tissues and organs with side effects, poor treatment effect, infection, etc., to improve delivery efficiency and utilization rate, avoid off-target effects or leakage of active substances, and solve the effect of poor treatment effect

Pending Publication Date: 2020-08-28
XIAN TISSUE ENG & REGENERATIVE MEDICINE RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, long-term use of these drugs can cause various side effects such as infection, kidney or liver damage
[0006] At the same time, the traditional and existing drugs for the treatment of skin lesions and ulcerative colitis not only have side effects on other tissues and organs, but also have poor therapeutic effects. A drug with specific therapeutic functions is needed to replace it to achieve better results and alleviate or Eliminate the side effects of the drug itself

Method used

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  • Targeting responsive release system and preparation method and application thereof
  • Targeting responsive release system and preparation method and application thereof
  • Targeting responsive release system and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Example 1 Targeted responsive release system loaded with MicroRNA-21

[0069] A target-responsive release system is provided, the target-responsive release system comprises a chimeric apoptotic body, the chimeric apoptotic body comprises an apoptotic body membrane and is wrapped in the apoptotic body membrane The mesoporous silicon dioxide nanoparticles in the apoptotic body membrane is the apoptotic body membrane derived from T cells, and the mesoporous silicon dioxide nanoparticle is loaded with MicroRNA-21. In some embodiments, MicroRNA-21 is loaded on the mesoporous nanoparticles through electrostatic interaction. In some embodiments, MicroRNA-21 breaks the disulfide bond through glutathione in the cytoplasm of the target cell, resulting in the release of MicroRNA-21 in the target cell. In a preferred embodiment, the MicroRNA-21 is labeled with Cy5.

Embodiment 2

[0070] Example 2 Targeted responsive release system loaded with curcumin

[0071] A target-responsive release system is provided, the target-responsive release system comprises a chimeric apoptotic body, the chimeric apoptotic body comprises an apoptotic body membrane and is wrapped in the apoptotic body membrane The mesoporous silica nanoparticle in the above, the apoptotic body membrane is the apoptotic body membrane derived from T cells, and the mesoporous silica nanoparticle is loaded with curcumin.

[0072] In some embodiments, after the curcumin is loaded in the pores of the mesoporous silica nanoparticles by physical adsorption, the mesoporous silica nanoparticles are encapsulated with polyglycerol dimethacrylate.

[0073] In some embodiments, the curcumin is released in the target cells responsively by degrading the polyglycerol dimethacrylate through the esterase in the target cells.

Embodiment 3

[0074] Example 3: Preparation of apoptotic body membrane

[0075] 1. Isolation, activation and identification of T cells

[0076] Primary T cells were derived from C57BL / 6 mouse splenocytes and cultured in RPMI-1640 medium containing 20% ​​FBS and 1% penicillin / streptomycin. First, 2 μg / ml CD3ε antibody was inoculated in a 6-well plate and incubated at 37°C for 4 h. Separate and take out the mouse spleen, grind the spleen fully with a sterile syringe handle, filter to form a cell suspension, add sterile erythrocyte lysate, gently blow and mix well, and lyse on ice for 10 minutes. Resuspend cells. Then filter the cell suspension with a 100 μm filter to remove cell clumps, add 2 μg / ml CD28 antibody and inoculate it into a 6-well plate pre-coated with CD3ε antibody, and cultivate T cells for 24-72 hours at 37°C and 5% CO2 After being activated, 1 μg / ml lipopolysaccharide was added to the culture system to act for 12 h to stimulate T cells. Morphological changes before and aft...

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Abstract

The invention provides a targeting responsive release system. The targeting responsive release system comprises a chimeric apoptotic corpuscle, the chimeric apoptotic corpuscle comprises an apoptoticcorpuscle membrane and mesoporous nanoparticles wrapped in the apoptotic corpuscle membrane, the apoptotic corpuscle membrane is an apoptotic corpuscle membrane derived from immune cells, and the mesoporous nanoparticles are loaded with active substances. The system provides an effective means for constructing a specific treatment product with a targeted delivery function and an accurate drug release function.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a target-responsive release system and its preparation method and application. Background technique [0002] Extracellular vesicles (EVs) are carriers for transmitting signal transduction molecules in intercellular communication, and can carry nucleic acids, proteins, lipids and other functional molecules to play a role. At the same time, the natural membrane endows extracellular vesicles with many advantages such as low immunogenicity, strong homologous targeting, long circulation time, and accessible biological barriers, which are unmatched by artificial materials. Inspired by these remarkable properties, extracellular vesicles are regarded as a new generation delivery system. Preparation of engineered extracellular vesicles modified with various bioactive molecules or targeting ligands to produce therapeutic effects at desired sites has become an attractive strategy f...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/46A61K47/04A61K47/32A61K31/12A61K31/7105A61P29/00
CPCA61K9/5176A61K9/5115A61K9/5138A61K31/12A61K31/7105A61P29/00Y02A50/30
Inventor 刘文娜
Owner XIAN TISSUE ENG & REGENERATIVE MEDICINE RES INST
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